Delayed Skin Reactions Research Articles

Protocolo de seguimento de pacientes com reações de pele tardias devido a procedimentos cardiológicos intervencionistas: seguimento de pacientes com reações de pele devido à radiação

Interventional cardiology procedures can generate high doses of ionizing radiation and delayed skin reactions in patients undergoing complex procedures with a substantial radiation dose level. Since 2014, we have implemented, in the cath lab, the monitoring of patients undergoing procedures with a substantial radiation dose level, to identify these patients and provide patient care support. We present two case reports of such patients, who are undergoing dermatological treatment. The implemented protocol provided specialized treatment for the patients and awareness of radiation safety among health workers.

(310) Severe Delayed Skin Reaction to Antiseptic Irrigation Solution Managed with Pinch Skin Grafting After Inflatable Penile Prosthesis Surgery: A Case Report

Abstract Introduction Inflatable penile prosthesis (IPP) surgery is a common procedure for treating erectile dysfunction, and skin preparation with antiseptic solutions is a standard practice to reduce infection risk. However, some antiseptic solutions, such as chlorhexidine-based Irrisept, have been associated with severe skin reactions. Several studies have reported cases of contact dermatitis, blistering, and chemical burns following the use of chlorhexidine-based antiseptic solutions before surgery. Objective This case report aims to highlight the potential risk of severe skin reactions when using Irrisept and other chlorhexidine antiseptic solutions during penile prosthesis surgery. It also explores the novel technique of pinch skin autografting used to salvage the implant and achieve successful wound healing after delayed skin necrosis. Methods 61-year-old male with a history of prostate cancer and erectile dysfunction who underwent insertion of an IPP. Results The patient's penile shaft developed blisters 3 weeks post-implantation, which progressed to full-thickness necrosis despite conservative treatment. The distribution and location of the reaction led to the hypothesis that it was caused by the chlorhexidine-based Irrisept antiseptic. The antiseptic solution used copiously throughout the case and 10CC was injected under pressure into the drain which also may explain the reaction observed. The patient underwent wound debridement and was treated with pinch skin autografts from the bilateral thighs. The autografts resulted in 95% epithelialization with excellent cosmetic outcomes with no other complications. To the best of our knowledge, this is the first reported case of Irrisept-induced delayed skin necrosis and the use of pinch skin grafting to salvage the implant after penile prosthesis surgery. Conclusions Skin reactions to Irrisept antiseptic solution during penile prosthesis surgery are rare but can be severe. Surgeons should be cautious and consider alternative skin preparation methods in patients with a history of skin allergies or sensitivities. This case also highlights the potential of pinch skin autografting as a salvage technique for post-IPP skin reactions. A multidisciplinary approach involving reconstructive burn surgeons and specialty wound care teams may be beneficial in optimizing outcomes in such cases. Disclosure No.

Removal of incorrect penicillin allergy labels in a UK hospital

ObjectivesPenicillin allergy records are common, often incorrect and are associated with broad spectrum antibiotic use. We piloted a pharmacist-led multidisciplinary penicillin allergy de-labelling daily ward round to determine the opportunity for penicillin allergy de-labelling in a UK hospital. MethodsA daily ward round, delivered by antibiotic pharmacists or junior doctors, identified adult medical and surgical patients between 7 November 2022 and 31 January 2023 with a penicillin allergy record that was preventing first-line penicillin use. An allergy history was taken before risk stratifying likelihood of future harm from penicillin re-exposure and an allergy testing method was determined (direct de-label on history alone or after direct drug provocation testing). After successful allergy de-label, the antibiotic was switched to a penicillin antibiotic. ResultsOf 7214 inpatients during the study period, 1133 (15.7%) had a penicillin allergy record. Of 285 allergy histories taken, 105 (36.8%) met high-risk criteria, 45 (15.8%) met low-risk criteria eligible for direct de-label and 73 (25.6%) met criteria eligible for direct drug provocation testing. We were unable to obtain a history for 61 (21.4%) patients. Of 45 low-risk patients eligible for direct de-label, 40 (88.9%) were de-labelled of whom 24 (53.3%) were switched to a penicillin antibiotic. Of 73 patients with a low-risk allergy history eligible for direct drug provocation testing, 16 (21.9%) received direct drug provocation testing, of whom 9 were switched to a penicillin antibiotic. Two direct de-label patients experienced harm (thrush within 5 days and delayed skin reaction after day 5); none of the direct drug provocation testing patients had a reaction by day 5. The switches resulted in reduced alternative antibiotic use by 173 Daily Defined Doses (DDDs). DiscussionPenicillin allergy de-labelling patient pathway delivered by pharmacists and junior doctors was safe and effective and well accepted by patients and the wider clinical teams.

P09 Non-allergist Removal of Incorrect Penicillin Allergy Labels (RIPAL) in a UK hospital

Abstract Objectives We piloted a pharmacist-led multidisciplinary penicillin allergy de-labelling (PADL) daily ward round to determine the opportunity for PADL in a UK hospital. Methods A daily ward round, delivered by either an antibiotic pharmacist or a junior doctor, identified adult medical and surgical patients between 7 November 2022 and 31 January 2023 with a penicillin allergy (penA) record that was preventing first-line penicillin use. An allergy history was taken before risk stratifying likelihood of future harm from penicillin re-exposure and an allergy testing method was determined [de-label on history (DOH) or after direct drug provocation testing (DDPT)]. Following successful de-label, in agreement with the responsible clinician, the antibiotic was switched to a penicillin antibiotic. Results Of 7214 inpatients during the study period, 1133 (15.7%) had a penA record. Of 285 allergy histories taken, 105 (36.8%) met high-risk criteria, 45 (15.8%) met low-risk criteria eligible for DOH, 73 (25.6%) met low-risk criteria eligible for DDPT and we were unable to obtain a history from 62 (21.8%) patients. Of 45 low-risk patients eligible for DOH, 40 (88.9%) were de-labelled of which 24 (53.3%) were switched to a penicillin antibiotic. Of 73 patients with a low-risk allergy history eligible for DOC, 16 (21.9%) received DDPT, of which nine were switched to a penicillin antibiotic to complete their antibiotic course. Two DOH patients experienced harm (thrush within the first 5 days and delayed skin reaction after day 5), none of the DPTs had a reaction by day 5. The switches resulted in 170 DDDs of penicillin use (predominantly amoxicillin) and reduced alternative antibiotic use by 174 DDDs (predominantly meropenem and levofloxacin). Conclusions Penicillin allergy de-labelling patient pathway delivered by pharmacists and junior doctors was safe and effective and well accepted by patients and the wider clinical teams. Further work is required to optimize and streamline these patient pathways to maximize patient and health system benefit.

Development, preparation, and evaluation of a novel non-adjuvanted polyvalent dermatophytes vaccine

Ringworm is a worldwide distributed contagious disease infecting both man and animals that constitute an economic, zoonotic, and health problem concern all over the world. During the last decade, attention has been directed to vaccination as an ideal approach to the control of such diseases. In the present study, non-adjuvanted polyvalent vaccines were prepared from locally isolated hot and virulent dermatophyte species, namely Trichophyton verrucosum (T. verrucosum), Trichophyton mentagrophytes (T. mentagrophytes), and Microsporum canis (M. canis) were immunologically evaluated. The prepared vaccine evaluation was focused on the aspects of immunogenicity and protective efficacy using guinea pigs. Both in its living or inactivated forms, the vaccine-induced significant humoral and cell-mediated immune responses and achieve proper protection of guinea pigs against challenging infections with homologous and heterologous dermatophyte strains. On the other hand, investigations on dermatophyte exo-keratinases showed that it was better produced and more expressed in a mineral-based medium containing pure keratin (3 g/L) than in the same medium with human hair supplementation (2.6 g/L). The maximum dermatophyte productivity of exo-keratinases was found to be between 18 and 21 days post-incubation. Using sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE), two fractions with molecular weights of 40 kDa (fraction I) and 28 kDa (fraction II) have been identified in the culture filtrate of the three involved dermatophyte species. Both fractions demonstrated keratinolytic activity. The specific activity of the isolated keratinases (number of Keratinase units (KU)/mg protein) was stronger in fraction I, where it reached 18.75, 15.38, and 14 KU/mg protein as compared to 12.9, 8.74, and 12 KU/mg protein in fraction II of T. verrucosum, T. mentagrophytes, and M. canis, respectively. The dermatophyte exo-keratinases proved to be immunogenic as they stimulated high keratinase-specific antibody titers and induced strong delayed skin hypersensitivity reactions in vaccinated animals. Anti-keratinase-specific IgG was detected in sera of guinea pigs immunized with the inactivated or living polyvalent dermatophyte vaccines by a homemade enzyme-linked immunosorbent assay (ELISA) using dermatophyte exo-keratinases as coating antigen. The intradermal injection of dermatophyte exo-keratinases induced specific delayed skin reactions in guinea pigs immunized with the inactivated or the living polyvalent dermatophyte vaccines. The intradermal injection of dermatophyte exo-keratinases in the control non-sensitized guinea pigs was associated with itching, swelling, and bloody scar formation, however, no skin indurations were formed. The development of those post-exo-keratinases injection reactions in the control non-sensitized apparently healthy guinea pigs group, suggests an exo-keratinases possible role in the pathogenesis of dermatophytosis.

Study of Excipients in Delayed Skin Reactions to mRNA Vaccines: Positive Delayed Intradermal Reactions to Polyethylene Glycol Provide New Insights for COVID-19 Arm.

Skin local reactions to mRNA COVID-19 vaccines have been linked to the use of vaccine excipients. The aim of the study is to evaluate the role of skin testing excipients in delayed skin reactions due to mRNA COVID-19 vaccines. Skin testing among a group of healthcare workers with skin reactions due to mRNA vaccines was performed. Patch testing and intradermal testing (IDT) with polyethylene glycol (PEG)-400, PEG-2000, trometamol, and 1,2-dimyristoyl-sn-glycero-3-phosphocholine were performed. Healthcare workers without skin reactions to vaccines were used for skin testing as controls. Thirty-one healthcare workers (from a total of 4315 vaccinated healthcare workers) experienced cutaneous adverse vaccine reactions. Skin testing was performed in sixteen of the healthcare workers (11 delayed large local reactions (DLLR) and 5 widespread reactions). Positive IDT for PEG-2000 1% in DLLR was seen in 10 (90.9%) patients, in comparison with one (16.6%) individual with a delayed widespread reaction. Delayed positive IDT reactions for PEG-2000 1% on day 2 were observed in three (27.3%) patients with DLLR. Patch testing of the excipients was negative. Among 10 controls, only one exhibited a transient positive IDT reaction to PEG-2000 1%. Immediate and delayed reactions to IDT are frequently detected in patients with DLLR. The observation of positive delayed intradermal reactions to PEG disclosed only in patients with DLLR reinforces a possible role of PEG in the development of these reactions. Skin testing of other excipients is of little importance in clinical practice.

Delayed skin reactions after the second dose of mRNA vaccines against SARS-CoV-2.

Delayed skin reactions after the second dose of mRNA vaccines against SARS-CoV-2.

Delayed eczematous skin reaction as an adverse drug reaction to immunoglobulin infusions: A case series

BackgroundPompholyx and eczematous reactions are known adverse reactions to intravenous immunoglobulins (IVIg) infusion, but little is known about their clinical characteristics, associated outcomes and management. ObjectiveTo describe IVIg-induced eczematous skin reactions. MethodsWe conducted a retrospective study on cases of delayed skin reactions post-IVIg infusion notified to the French Regional Pharmacovigilance Centre from 1985 to 2020. ResultsA total of 27 patients were identified, of whom 85% were male. IVIg infusions were given in a neurological indication in 82% of cases. Eczematous skin reactions occurred in two-thirds of cases after the first infusion, with a median time to onset of 11 days. Palmoplantar pompholyx was the most common presentation, being seen in 63% of patients. Other eruptions were erythemato-squamous or maculopapular. Eight patients were classified as severely affected and developed extensive lesions (>50% BSA). One third of the 27 patients required hospitalization. All of the severe eczematous reactions involved males receiving high doses of IVIg for neurological diseases. Biopsies of severe cases revealed a common non-specific eczematous pattern. Relapses were frequent and more severe than the initial reaction. Reintroduction of the same IVIg product consistently resulted in relapse, whereas switching IVIg type produced relapse in only 53% of patients. ConclusionWe present the largest retrospective study of delayed skin reactions after IVIg infusions. This side-effect may be severe and have a polymorphic presentation. Relapse occurs frequently but less consistently after IVIg switch.

Safe De-Labeling of Patients at Low Risk of Penicillin Allergy in Denmark

Introduction: Penicillin allergy is suspected in 10% of hospital inpatients but can be disproved in 90% of cases. Direct oral provocation without preceding tests among low-risk patients has proven to be safe in studies of both children and adults and is gaining use across the world. The aims of this study were to investigate the rate of severe allergic reactions to direct oral drug provocation, without preceding tests, in penicillin allergy patients stratified to be at low risk, as well as to examine if these patients have barriers to penicillin allergy de-labeling and future use of penicillins. Methods: Adult patients referred to a university hospital allergy clinic with a suspected penicillin allergy were prospectively risk evaluated. Patients stratified to be at low risk were offered a direct oral provocation with a single-dose amoxicillin followed by 4 days of continued treatment. The same risk stratification criteria were applied to a larger retrospective cohort. Results: In the prospective study population, 202 patients had a direct oral drug provocation and 20 (10%) were positive. There were no cases of anaphylaxis or severe delayed hypersensitivity. Fifteen reactions were benign rashes with onset >1 day after initial dosing, and 13 of these were maculopapular rashes. The same low-risk criteria were applied retrospectively to patients in a drug provocation database, and 1,759 patients fulfilled the criteria; of these, 10% had positive provocations, and there were no cases of anaphylaxis or severe delayed hypersensitivity. De-labeled patients in the prospective study reported not to fear future penicillin intake, after prolonged provocation. Conclusion: The risk stratification criteria for identifying low-risk patients for the oral drug provocation test without prior skin testing were safe in terms of avoiding anaphylaxis or severe delayed hypersensitivity. Benign delayed skin reactions still occurred, and access to allergy advice and follow-up is necessary.

Delayed skin reactions and mRNA vaccines against SARS-CoV-2: correspondence.

Delayed skin reactions and mRNA vaccines against SARS-CoV-2: correspondence.

A Case of Progestogen Hypersensitivity

Progestogen hypersensitivity (PH) is a cyclical dermatosis that occurs in fertile women during the luteal phase of the menstrual cycle. The clinical presentation is variable and non-specific. We report the case of a 42-year-old woman with a 10-year history of itchy skin lesions that recurred monthly. Determined with her basal body temperature chart, her skin symptoms were related to progesterone surges. Skin examinations revealed multiple and extensive monomorphic red papules, mainly on her arms and legs, as well as on her chest and back. She had no history of associated fever or dyspnea. Her hair, nails and mucous membranes were normal. A blood test at the time of the worst skin eruption revealed mild elevation of serum thymus and activation-regulated chemokines and eosinophilia. Her total serum IgE level was normal. She showed a delayed skin reaction to progesterone. Ultra-low-dose combined oral contraceptives (COCs) improved her symptoms by suppressing ovulation. Accordingly, a diagnosis of progestogen hypersensitivity was made. A T-helper (Th)2 response rather than a Th1 response was suggested to be involved in this case. Atopic dermatitis (AD) can be classified into the major extrinsic type with high serum IgE levels and the minor intrinsic type with normal IgE levels. PH and AD share similarities in that they present with eczema, IgE-mediated sensitization and delayed hypersensitivity responses, and their pathophysiology remains to be fully elucidated because of their heterogeneous aspects. The symptoms of this case were in line with IgE-low AD rather than IgE-high AD, which implicates endogenous progesterone as a trigger.

Delayed skin reaction after mRNA-1273 vaccine against SARS-CoV-2: a rare clinical reaction

BackgroundThe coronavirus disease 2019 (COVID‐19) is associated with a wide clinical spectrum of skin manifestations, including urticarial, vesicular, vasculitic and chilblain‐like lesions. Recently, delayed skin reactions have been reported in 1% individuals following mRNA vaccination against SARS-CoV-2. The exact pathophysiology and the risk factors still remain unclear.Patients and methods6821 employees and patients were vaccinated at our institutions between February and June 2021. Every patient received two doses of the mRNA-1273 vaccine in our hospitals, and reported back in case of any side effects which were collected in our hospital managed database.ResultsEleven of 6821 vaccinated patients (0.16%) developed delayed skin reactions after either the first or second dose of the mRNA-1273 vaccine against SARS-CoV-2. Eight of 11 patients (73%) developed a rash after the first dose, while in 3/11 (27%), the rash occurred after the second dose. More females (9/11) were affected. Four of 11 patients required antihistamines, with two needing additional topical steroids. All the cutaneous manifestations resolved within 14 days. None of the skin reactions after the first dose of the vaccine prevented the administration of the second dose. There were no long-term cutaneous sequelae in any of the affected individuals.ConclusionOur data suggests that skin reactions after the use of mRNA-1273 vaccine against SARS-CoV-2 are possible, but rare. Further studies need to be done to understand the pathophysiology of these lesions.

Delayed Cutaneous Hypersensitivity Reaction to Vaxzevria (ChAdOx1-S) Vaccine against SARS-CoV-2.

Recently, an increasing number of cases with delayed cutaneous reaction after immunization with mRNA-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been reported. This adverse reaction, which is considered a delayed-type or T cell-mediated hypersensitivity reaction, has been described for the Moderna (mRNA-1273) and Comirnaty (Pfizer/BioNTech, BNT162b2) vaccines. We describe a delayed large local cutaneous reaction in a patient who received the viral vector vaccine Vaxzevria (ChAdOx1-S, AstraZeneca). The time course and clinical symptoms of delayed skin reaction after mRNA vaccines have a similar pattern that we recognized in our patient after Vaxzevria vaccination. This phenomenon has not been described in the Vaxzevria clinical trials and is to our knowledge the first report of this adverse reaction to a vector-based SARS-CoV-2 vaccine. With this, we hope to raise awareness about delayed injection site reactions that also occur after viral vector vaccines and to encourage additional reporting and patient education regarding the cutaneous reactions after coronavirus disease 2019 (COVID-19) vaccination.

Skin Reactions in Patients With Multiple Sclerosis Receiving Cladribine Treatment.

ObjectiveTo report 77 patients with multiple sclerosis (MS) who developed skin-related adverse events (AEs) following treatment with cladribine.MethodsWe evaluated our prospective bicentric cladribine cohort. Cladribine-treated patients with a skin AE were identified.ResultsTwo hundred thirty-nine cladribine-treated patients with MS were evaluated. Seventy-seven patients (32%) showed at least 1 skin AE at median 1 month after cladribine initiation (range: 1–12). Within first 3 months following last cladribine exposition, hair thinning (n = 28, 12%), skin rash (n = 20; 8%), mucositis (n = 13, 5%), and pruritus (n = 6, 3%) were observed. Furthermore, 35 patients (15%) developed herpes virus infections (time since last cladribine exposition: median 83 [range: 10–305]). In 15 patients, herpes zoster infection was severe (CTCAE grade ≥ 3) and required hospitalization. Delayed skin AEs (≥3 months after a cladribine treatment cycle) involved 1 case of leukocytoclastic vasculitis and 2 cases of alopecia areata. Finally, 2 patients presented with in total 3 isolated precancerous lesions (1 leukoplakia simplex and 2 actinic keratosis) and 1 patient developed a squamous cell carcinoma.ConclusionSkin AEs are common in patients with MS treated with cladribine. Until risk management plans have been adjusted to include these phenomena, clinicians should perform a thorough clinical follow-up and in suspicious cases seek early interdisciplinary support. In light of the observed delayed skin reactions, we further emphasize the necessity of careful clinical surveillance of cladribine-treated patients for yet undescribed secondary autoimmune events.Classification of EvidenceThis study provides Class IV evidence that skin-related AEs are frequent in patients with MS following cladribine in a real-world setting.

Иммунопатогенные свойства SARS-CoV-2 как основа для выбора патогенетической терапии

Guinea-pigs were immunized via footpads with sheep red blood cells (SRBC) in saline. Histological examination of erythematous skin reaction was performed and effects of cyclophosphamide (CY) or BCG pre-treatment on the skin reaction were examined. Delayed-in-onset erythematous skin reaction accompanied by substantial basophil infiltration was elicited in guinea-pigs immunized with SRBC in saline. The erythema was augmented in size by CY which was injected 2 days before immunization. The reaction may be comparable to Jones-Mote type. In BCG pre-treated guinea-pigs, basophil infiltration at the skin reaction sites was reduced in number, but significant inhibition of macrophage migration was not detected in the presence of SRBC antigen. The reaction may be intermediate between Jones-Mote and the tuberculin type. Comparability of delayed skin reactions in guinea-pigs and delayed footpad reactions in mice or hamsters against SRBC is discussed.

1094. Safety of Administering Cefazolin vs. Other Antibiotics in Penicillin Allergic Patients with Anaphylaxis for Surgical Prophylaxis

BackgroundApproximately 10% of patients report a history of penicillin allergy. Recent literature suggests cross-reactivity between cephalosporins and penicillins are due to side-chain similarities. Since cefazolin has a unique side-chain from other β lactams, it can be safely administered in penicillin-allergic patients for surgical prophylaxis. Since October 2018, our hospital updated all surgical prophylaxis preprinted orders to use cefazolin in penicillin-allergic patients, except in those with histories of cefazolin-specific allergy or delayed skin reactions (e.g., Stevens–Johnson syndrome). This study aims to retrospectively determine outcomes and safety of cefazolin as compared with other antibiotics for surgical prophylaxis in penicillin-allergic patients with histories of anaphylaxis prior to implementation of cefazolin preprinted orders.MethodsAll patients with reported anaphylactic reactions to penicillins prescribed surgical prophylaxis from October 9, 2017 to October 9, 2018 were included. Patients were stratified based on antibiotic received (i.e., cefazolin, clindamycin, vancomycin, other antibiotic) and a retrospective chart review was performed to assess for outcomes and safety.ResultsOne-thousand-seventy-three prescriptions for prophylactic antibiotics were identified. Of these, 223 cases met inclusion with histories of anaphylaxis to pencillins: 72 (32%) cefazolin, 70 (31%) clindamycin, 34 (15%) vancomycin, and 47 (21%) other antibiotics. General and orthotrauma surgeries used the most cefazolin in penicillin-allergic patients, while gynecology clindamycin and thoracics vancomycin. Amongst those receiving cefazolin, no critical incidents of allergic reactions were reported and the rates of adverse events, such as pruritus, hives and rash, did not differ between any antibiotic group.ConclusionCefazolin appears to be a safe option for surgical prophylaxis in patients with history of penicillin anaphylaxis. No differences in incidences of allergic reactions, complications or surgical delays were reported, as compared with alternate antibiotics. Further larger studies are needed to confirm our findings and determine rates of adverse events associated with the various antibiotic regimens.Disclosures All authors: No reported disclosures.

Cross-elicitation responses to 2-methoxymethyl-p-phenylenediamine in p-phenylenediamine highly allergic volunteers using allergy alert test: the Italian experience.

Background. Allergic contact dermatitis after exposure to p-phenylenediamine (PPD)-containing hair dye products is a common and important clinical problem. Because there is a high rate of cross-elicitation of allergic contact dermatitis to other important hair dye products (such as p-toluene diamine [PTD] and other aminophenol hair dyes) in PPD allergic patients, safer alternative dyes with excellent hair coloring options are needed. We studied 2-methoxy methyl-PPD (Me-PPD), a chemical derivative of PPD for tolerance versus cross-elicitation in a cohort of eight PPD-allergic volunteers. Objective. To study tolerance to Me-PPD in a PPD highly allergic Italian cohort. Methods. Eight volunteers with a history of contact dermatitis to hair dyes or other PPD-containing chemicals and positive patch tests to 1% PPD in petrolatum, were recruited to study their immediate and delayed skin reactivity to PPD, vehicle control and 2-methoxy-methyl-PPD (Me-PPD), using the allergy alert test (simulating hair dyeing conditions) on volar forearm skin. This is a short-contact open patch test. Results. All eight volunteers reacted to PPD allergy alert test (100%); none reacted to vehicle (0%), and seven of eight reacted to Me-PPD allergy alert test (88%). However, in those seven volunteers who exhibited cross-elicitation to Me-PPD, their aggregate skin test reactivity to Me-PPD was significantly less than that of PPD (figure 3, p minore 0.0062, highly significant, paired two-tailed, students t test). Conclusions. Me-PPD may offer a safer alternative for PPD-allergic patients with an absent or reduced elicitation response in the allergy alert test simulating hair dye use conditions. Even patients with strong patch test reactions, with appropriate selection by allergy alert test and counselling, may be able to tolerate hair dyeing with Me-PPD containing products.

Delayed hypersensitivity to new oral anticoagulants. Demonstration of cross reactivity for the drug category and definition of non-irritant concentrations for patch tests.

The current therapy with direct trombin inhibitors (DTI) is indicated for the prevention of stroke in non-valvular atrial fibrillation. Side effects are reported, particularly skin hypersensitivity, for this whole category of drugs as well as for other modern antiplatelet and anticoagulant drugs. For their clinical features, these reactions appear as delayed T-cell mediated drug hypersensitivity, but at present there are no diagnostic methods of investigation. We reported a case of delayed skin reaction to edoxaban and we found the non-irritant concentration for patch test in the whole category of drugs. The patch test resulted positive for edoxaban. A successive challenge with alternative DTIs and/or a switch to warfarin is proposed as alternative therapy.

The Safety and Tolerability of Topically Delivered Kynurenic Acid in Humans. A Phase 1 Randomized Double-Blind Clinical Trial

Scarring is a consequence of biological tissue repair following trauma. Currently, there are no generally agreed ways to prevent scarring. Recently, kynurenic acid has shown to be a potent modulator of extracellular matrix deposition and remodeling. Kynurenic acid can reduce matrix deposition and other fundamental characteristics of fibrosis in vitro and in vivo. Specifically, kynurenic acid has shown to increase matrix metalloproteinase-1 activity and subsequently reduce collagen deposition in a rabbit ear scar model. In the present study kynurenic acid cream in different concentrations was topically applied on healthy skin on volunteers to assess skin reactions and skin sensitivity in both acute and chronic application settings. Skin reactions were assessed, and concentrations for kynurenic acid were assessed both form serum and urine. Results showed to acute or delayed skin reactions. Kynurenic acid was not detectable in blood at any time point, and only trace elements of kynurenic acid were found in urine. This study supports safety and tolerability of topically administered FS2 when using a liposomal, compounding base carrier.

Delayed Allergic Cutaneous Hypersensitivity to Icodextrin

Rashes pose a unique challenge to general internists. Here we present a case of a 51-year-old female with end-stage renal disease (ESRD) on peritoneal dialysis who presented to a General Internal Medicine clinic with a vesiculobullous rash on palms and soles 6 months after using icodextrin dialysate, a widely used osmotic agent in peritoneal dialysis. The investigations were positive for an elevated eosinophil count, elevated IgE level and a skin biopsy consistent with an allergic reaction. Her symptoms and labs normalized after stopping icodextrin. There are some reports of allergic reactions to icodextrin which usually occur within a month of initiation of the agent and are self-limiting. Here we hope to report a case of a reaction that occurred 6 months after using icodextrin.
 Resume
 Les éruptions cutanées posent un défi particulier aux internistes généraux. Nous rapportons ici le cas d’une femme de 51 ans atteinte d’insuffisance rénale terminale (IRT), sous dialyse péritonéale, qui se présente à une clinique de médecine interne générale avec une éruption cutanée vésiculo-bulleuse sur les paumes et la plante des pieds. Depuis six mois, la patiente utilise un dialysat d’icodextrine, un agent osmotique largement utilisé en dialyse péritonéale. Les analyses ont révélé une numération élevée des éosinophiles, un taux élevé d’IgE et une biopsie cutanée a indiqué la présence d’une réaction allergique. Les symptômes et les résultats d’analyses se sont normalisés après l’arrêt de l’icodextrine. Des réactions d’allergie à l’icodextrine ont déjà été rapportées, mais celles-ci surgissent habituellement dans le mois suivant le début de l’usage de l’agent et se résorbent d’elles-mêmes. Nous désirons signaler un cas de réaction survenue six mois après le début de l’utilisation de l’icodextrine.