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Botulinum toxin and hyaluronic acid (HA) filler injections are popular minimally invasive cosmetic procedures owing to their convenience, efficiency, and durability; however, adverse reactions often occur.We describe the delayed hypersensitivity reaction that occurred after sequential injections of botulinum toxin and HA filler.The histopathologic and dermatoscopic findings suggested a delayed hypersensitivity reaction with the formation of a dermal foreign body granuloma. The rash resolved 2 months following treatment with antihistamines and topical steroids cream.We assume that local trauma during the blepharoplasty stimulated an immune response, which was the basis for this complication.

In evaluating adverse drug reactions (ADRs), patch tests (PTs), skin prick tests (SPTs), and intradermal tests (IDTs) are useful tools for identifying responsible drugs and finding safe alternatives. Their diagnostic value depends on the clinical features of the ADR and on the drug tested. PTs have a good sensitivity in assessing acute generalized exanthematous pustulosis and drug rash with eosinophilia and systemic symptoms. SPTs done with all drugs except opiates are used for immediate hypersensitivity reactions. IDTs seem sensitive for immediate hypersensitivity reactions to beta-lactam antibiotics, iodinated contrast media, heparins, general anesthetics, and platinum salts.

CX3CR1high myeloid cells in the small intestine mediate the induction of oral tolerance by driving regulatory T (Treg) cells. Bacterial metabolites, e.g. pyruvate and lactate, induce a dendrite extension of CX3CR1high myeloid cells into the intestinal lumen via GPR31. However, it remains unclear whether the pyruvate–GPR31 axis is involved in the induction of oral tolerance. Here, we show that pyruvate enhances oral tolerance in a GPR31-dependent manner. In ovalbumin (OVA)-fed Gpr31-deficient mice, an OVA-induced delayed-type hypersensitivity response was substantially induced, demonstrating the defective induction of oral tolerance in Gpr31-deficient mice. The percentage of RORγt+ Treg cells in the small intestine was reduced in Gpr31-deficient mice. In pyruvate-treated wild-type mice, a low dose of OVA efficiently induced oral tolerance. IL-10 production from intestinal CX3CR1high myeloid cells was increased by OVA ingestion in wild-type mice, but not in Gpr31-deficient mice. CX3CR1high myeloid cell-specific IL-10-deficient mice showed a defective induction of oral tolerance to OVA and a decreased accumulation of OVA-specific Treg cells in the small intestine. These findings demonstrate that pyruvate enhances oral tolerance through a GPR31-dependent effect on intestinal CX3CR1high myeloid cells.

Background Skin rash often occurs upon oral administration of amoxicillin in children, due to non-immediate hypersensitivity. However, information on delayed hypersensitivity to amoxicillin is scarce. Moreover, the appropriate diagnostic method and actual diagnostic rate of delayed hypersensitivity to amoxicillin among Japanese children are unclear. We conducted intradermal tests (IDTs) and drug provocation tests (DPTs) and retrospectively investigated the proportion of children with a definitive diagnosis of non-immediate hypersensitivity to amoxicillin. We then evaluated the characteristics of patients with a positive allergic workup. Methods We enrolled children referred for suspected findings of mild or moderate non-immediate hypersensitivity to amoxicillin between August 2018 and March 2020. If the IDT in the delayed phase was negative, DPT with amoxicillin (60–90 mg/kg/day) was performed for 7 days. Non-immediate hypersensitivity to amoxicillin was defined when IDT or DPT was positive. We evaluated the potential of the drug-induced lymphocyte stimulation test (DLST) to reveal hypersensitivity to amoxicillin. Results This study enrolled 27 children. Fourteen children (52%) had hypersensitivity to amoxicillin, of whom 12 had positive IDTs and two had positive DPTs. No differences in age, sex, history of allergic disease, days from oral use to symptom onset, type of rash at symptom onset, generalized rash, and DLST results were observed between the hypersensitivity and non-hypersensitivity groups. Conclusions Examination should be performed for children with mild or moderate reactions because positive cases have no significant features and half of the suspected cases are negative.

ObjectivesDrug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, delayed hypersensitivity reaction (DHR). We observed DRESS to inhibitors of interleukin 1 (IL-1) or IL-6 in a small group of patients with Still’s disease with atypical lung disease. We sought to characterise features of patients with Still’s disease with DRESS compared with drug-tolerant Still’s controls. We analysed human leucocyte antigen (HLA) alleles for association to inhibitor-related DHR, including in a small Kawasaki disease (KD) cohort.MethodsIn a case/control study, we collected a multicentre series of patients with Still’s disease with features of inhibitor-related DRESS (n=66) and drug-tolerant Still’s controls (n=65). We retrospectively analysed clinical data from all Still’s subjects and typed 94/131 for HLA. European Still’s-DRESS cases were ancestry matched to International Childhood Arthritis Genetics Consortium paediatric Still’s cases (n=550) and compared for HLA allele frequencies. HLA association also was analysed using Still’s-DRESS cases (n=64) compared with drug-tolerant Still’s controls (n=30). KD subjects (n=19) were similarly studied.ResultsStill’s-DRESS features included eosinophilia (89%), AST-ALT elevation (75%) and non-evanescent rash (95%; 88% involving face). Macrophage activation syndrome during treatment was frequent in Still’s-DRESS (64%) versus drug-tolerant Still’s (3%; p=1.2×10−14). We found striking enrichment for HLA-DRB1*15 haplotypes in Still’s-DRESS cases versus INCHARGE Still’s controls (p=7.5×10-13) and versus self-identified, ancestry-matched Still’s controls (p=6.3×10−10). In the KD cohort, DRB1*15:01 was present only in those with suspected anakinra reactions.ConclusionsDRESS-type reactions occur among patients treated with IL-1/IL-6 inhibitors and strongly associate with common HLA-DRB1*15 haplotypes. Consideration of preprescription HLA typing and vigilance for serious reactions to these drugs are warranted.

As elexacaftor/tezacaftor/ivacaftor has proven to have robust clinical efficacy for eligible persons with cystic fibrosis, desensitization should be offered to those with maculopapular eruption hypersensitivity reactions to achieve tolerance. As presented in this case, if provided with tools for crushing and mixing the medication, a successful escalation protocol can be completed at home without coordinating the help of a compound pharmacy.

Background As more people become vaccinated against the SARS‐CoV‐2 virus, reports of delayed cutaneous hypersensitivity reactions are beginning to emerge. Methods In this IRB‐approved retrospective case series, biopsy specimens of potential cutaneous adverse reactions from the Pfizer‐BioNTech or Moderna mRNA vaccine were identified and reviewed. Clinical information was obtained through the requisition form, referring clinician, or medical chart review. Results Twelve cases were included. Histopathological features from two injection‐site reactions showed a mixed‐cell infiltrate with eosinophils and a spongiotic dermatitis with eosinophils. Three biopsy specimens came from generalized eruptions that showed interface changes consistent with an exanthematous drug reaction. Three biopsy specimens revealed a predominantly spongiotic pattern, consistent with eczematous dermatitis. Small‐vessel vascular injury was seen in two specimens, which were diagnosed as urticarial vasculitis and leukocytoclastic vasculitis, respectively. There were two cases of new‐onset bullous pemphigoid supported by histopathological examination and direct immunofluorescence studies. Eosinophils were seen in 10 cases. Conclusions Dermatopathologists should be aware of potential cutaneous adverse reactions to mRNA‐based COVID‐19 vaccines. Histopathological patterns include mixed‐cell infiltrates, epidermal spongiosis, and interface changes. Eosinophils are a common finding but are not always present. Direct immunofluorescence studies may be helpful for immune‐mediated cutaneous presentations such as vasculitis or bullous pemphigoid.

A 54-year-old man presented with worsening bilateral rashes on legs and arms 7 days after receiving his BNT162b2 mRNA COVID-19 (Pfizer) vaccine booster. He developed burning on his palms about 5 days after receiving the booster. On day 6, he observed significant edema on his fingers and palms in addition to thin erythematous papules on his forearms. On day 7, he developed edema on his bilateral dorsal feet, and thin erythematous plaques on his shins. He stated that the rashes were pruritic. He had no rashes following the first two doses of the Pfizer vaccine. He denied having any history of skin disease, autoimmune disease, or allergies. Physical examination revealed multiple thin erythematous papules coalescing into thin plaques on his flexor forearms, and thin erythematous plaques on his dorsal feet (Figure 1). Three 4-mm punch biopsies were performed on his left flexor forearm. The biopsies were carried out at papules present for different lengths of time. Papules at biopsy sites "A," "B," and "C" were present for approximately 24-36 hours, 12-18 hours, and 3-6 hours, respectively (Figure 1). (

Up to 10% of hospitalized patients have an antibiotic allergy label in their medical file, most frequently concerning penicillins. However, the vast majority of reported allergies to antibiotics does not represent a "true" allergy but are due to drug intolerance, idiosyncratic reactions or symptoms of the concurrent infectious disease. Since antibiotic allergy labels result in deviation from first-choice antimicrobial therapy, tackling the issue of incorrect antibiotic allergy labelling, already at young age, is a core element of antibiotic stewardship. In this article, we describe the structured approach to the patient with a presumed antibiotic allergy with emphasis on key elements of allergy-specific history taking and the limited risk of cross-allergic reactions between beta-lactam subclasses.

Background Sarcoptes scabiei is one of the most impactful mammalian parasites. There has been much research on immunological and clinical pathological changes associated with S. scabiei parasitism across a range of host species. This rich body of literature is complex, and we seek to bring that complexity together in this study. We first (1) synthesise narrative reviews of immunopathological relationships to S. scabiei infection to construct overarching hypotheses; then (2) undertake a systematic meta-analysis of primary literature on immunological and clinical pathological changes; and lastly (3) contrast our findings from the meta-analysis to our synthesis from narrative reviews. Methods We synthesised 55 narrative reviews into two overarching hypotheses representing type I and type IV immune responses to S. scabiei infection. We then systematically extracted all literature reporting immunological variables, acute phase proteins, oxidant/antioxidant status, and erythrocytic, hepatological and nephrological changes, calculating 565 effect sizes between controls and sarcoptic mange affected groupings, refining (simplifying) hypotheses from narrative reviews. Results Immunological and clinical pathological parameters were most often studied in dogs (n = 12) and humans (n = 14). Combining immunological and clinical pathological information across mammalian species (n = 19) helped yield general insights into observed disease responses. This is evidenced by interspecific consensus in 27 immunological and clinical pathology variables (6/26 type I hypersensitivity, 3/20 type IV hypersensitivity, 6/10 oxidant/antioxidant status, 3/6 acute phase protein, 4/7 erythrocytic, and 5/10 hepatological/nephrological). Conclusions Elevated IgE, eosinophils and mast cells in type I hypersensitivity response corresponded to what was described in narrative reviews. Results from type IV hypersensitivity response suggested typical antibody response, however cell-mediated response was less evident. Some consensus of acute phase protein response and shifted oxidant/antioxidant balance and slight evidence of anemia. We highlight the need for mange/scabies studies to more routinely compare immunological and clinical pathological changes against controls, and include collection of a more standardised suite of variables among studies.

T-cell-mediated drug hypersensitivity is responsible for significant morbidity and mortality, and represents a substantial clinical concern. The purpose of this article is to focus on T-cell reactions and discuss recent advances in disease pathogenesis by exploring the impact of tolerance mechanisms in determining susceptibility in genetically predisposed patients.Certain drugs preferentially activate pathogenic T cells that have defined pathways of effector function. Thus, a critical question is what extenuating factors influence the direction of immune activation. A large effort has been given towards identifying phenotypic (e.g., infection) or genotypic (e.g., human leukocyte antigen) associations which predispose individuals to drug hypersensitivity. However, many individuals expressing known risk factors safely tolerate drug administration. Thus, mechanistic insight is needed to determine what confers this tolerance. Herein, we discuss recent clinical/mechanistic findings which indicate that the direction in which the immune system is driven relies upon a complex interplay between co-stimulatory/co-regulatory pathways which themselves depend upon environmental inputs from the innate immune system.It is becoming increasingly apparent that tolerance mechanisms impact on susceptibility to drug hypersensitivity. As the field moves forward it will be interesting to discover whether active tolerance is the primary response to drug exposure, with genetic factors such as HLA acting as a sliding scale, influencing the degree of regulation required to prevent clinical reactions in patients.

Summary Metal hypersensitivity (MHS) and trunnionosis are being looked at more frequently. Both entities pose a difficult concern for surgeons and patients alike. This commentary highlights the similarities and differences between the 2 conditions. When a surgeon suspects either MHS or trunnionosis, both should be considered in the differential diagnosis. Both conditions are rare and should be considered a diagnosis of exclusion. The commentary proposes an outline on how to diagnose and treat the 2 entities.

The disease caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), ie, coronavirus disease 2019 (COVID-19), has become a global pandemic since it was first reported in Wuhan, China in December 2019. Its severe clinical manifestations, which often necessitate admission to intensive care units, and high mortality rate represent a therapeutic challenge for the medical community. To date, no drugs have been approved for its treatment, and various therapeutic options are being assayed to address the pathophysiological processes underlying the clinical manifestations experienced by patients. New and old drugs administered as monotherapy or in combination to immunologically compromised patients may favor the development of adverse drug reactions, including drug hypersensitivity reactions, which must be identified and managed accordingly. Given the lack of herd immunity and the high rate of viral contagion, new cases are expected to emerge in the coming months. Thus, the probability of more adverse reactions or even new clinical manifestations may increase in parallel. Allergists must receive updated information on these treatments, as well as on the management of possible drug hypersensitivity reactions.

A defining feature of protracted sepsis is development of immunosuppression that is thought to be a major driving force in the morbidity and mortality associated with the syndrome. The immunosuppression that occurs in sepsis is characterized by profound apoptosis-induced depletion of CD4 and CD8 T cells and severely impaired T cell function. OX40, a member of the TNF receptor superfamily, is a positive co-stimulatory molecule expressed on activated T cells. When engaged by OX40 ligand, OX40 stimulates T cell proliferation and shifts the cellular immune phenotype toward TH1 with increased production of cytokines that are essential for control of invading pathogens. The purpose of the present study was to determine if administration of agonistic Ab to OX40 could reverse sepsis-induced immunosuppression, restore T cell function, and improve survival in a clinically relevant animal model of sepsis. The present study demonstrates that OX40 agonistic Ab reversed sepsis-induced impairment of T cell function, increased T cell IFN-γ production, increased the number of immune effector cells, and improved survival in the mouse cecal ligation and puncture model of sepsis. Importantly, OX40 agonistic Ab was not only effective in murine sepsis but also improved T effector cell function in PBMCs from patients with sepsis. The present results provide support for the use of immune adjuvants that target T cell depletion and T cell dysfunction in the therapy of sepsis-induced immunosuppression. In addition to the checkpoint inhibitors anti-PD-1 and anti-PD-L1, OX40 agonistic Ab may be a new therapeutic approach to the treatment of this highly lethal disorder.

Lichenoid granulomatous dermatitis (LGD) is a histopathologic pattern with a band-like lymphocytic infiltrate, typical of lichenoid dermatitis, combined with dermal histiocytes and granulomatous inflammation. Prior reports have described cases of LGD caused by non-tuberculous mycobacteria, with evidence of intralesional acid-fast bacilli or mycobacterial DNA. Herein, we report a patient with pulmonary and extrapulmonary Mycobacterium tuberculosis infection who developed LGD. No evidence of M. tuberculosis was detected within the cutaneous lesions, suggesting a potential delayed-type hypersensitivity reaction to tuberculosis.

Penicillin refers to a group of beta-lactam antibiotics that are the first-line treatment for a range of infections. However, they also possess the ability to form novel antigens, or neoantigens, through haptenation of proteins and can stimulate a range of immune-mediated adverse reactions-collectively known as drug hypersensitivity reactions (DHRs). IgE-mediated reactions towards these neoantigens are well studied; however, IgE-independent reactions are less well understood. These reactions usually manifest in a delayed manner as different forms of cutaneous eruptions or liver injury consistent with priming of an immune response. Ex vivo studies have confirmed the infiltration of T cells into the site of inflammation, and the subsets of T cells involved appear dependent on the nature of the reaction. Here, we review the evidence that has led to our current understanding of these immune-mediated reactions, discussing the nature of the lesional T cells, the characterization of drug-responsive T cells isolated from patient blood, and the potential mechanisms by which penicillins enter the antigen processing and presentation pathway to stimulate these deleterious responses. Thus, we highlight the need for a more comprehensive understanding of the underlying genetic and molecular basis of penicillin-induced DHRs.

During the development of cosmetic formulations, in vitro and in vivo methods are essential tools used to reliably assess the skin irritation potential of a product or ingredient. Epicutaneous patch testing (single and/or multiple application protocols) has long been used as an initial in vivo method to screen for possible skin irritation properties of a substance or formulation. To confirm the mildness and dermatological and/or consumer acceptance of a product, use tests are often subsequently conducted. A study was therefore initiated to see how well patch test results correlate with use tests with respect to irritation elicited by skincare (leave-on) products.A number of different cosmetic formulations were assessed in both tests. Although the patch test results did not indicate substantial irritation potentials, immediate-type reactions (stinging and redness) were observed in some volunteers which disappeared within approx. 1 h. Although transient, these reactions suggested that consumer acceptance would probably be low and the studies were discontinued. Immediate-type reactions are rare but have been described for some substances used in cosmetics. These unexpected results were nevertheless intriguing and prompted the start of a journey to see if patch test protocols could be modified to assess these reactions. An occlusive short-term patch test protocol with an application period of 20 min was developed. Successful identification of the spontaneous reactions became possible. Furthermore, there was a correlation between the intensity of reactions observed in the short-term patch test and those observed in the controlled in-use studies. Short-term patch testing using the developed protocol can therefore reliably be used as a screening method, for example in the development and optimization of cosmetic formulations containing ingredients that could cause spontaneous reactions, for instance of non-immunological contact urticaria type.The lessons learned from this studies indicate that simple modifications of existing test protocols can lead to important insights into skin reactions. These modifications can then be used to create further building blocks in the development and optimization of test strategies for cosmetic formulations which offer reliable study designs for possible reactions product developers may encounter.Lors du développement de formulations cosmétiques, les méthodes in vitro et in vivo sont des outils essentiels utilisés pour évaluer de manière fiable le potentiel d'irritation cutanée d'un produit ou d'un ingrédient. Le test épicutané (protocoles d'application uniques et / ou multiples) est utilisé depuis longtemps comme méthode initiale in vivo pour dépister les éventuelles propriétés d'irritation cutanée d'une substance ou d'une formulation. Afin de confirmer la douceur et l'acceptation dermatologique et / ou consommateur d'un produit, des tests d'usage sont souvent effectués ultérieurement. Une étude a donc été initiée pour voir dans quelle mesure les résultats des tests épicutanés correspondent aux tests d'usage en ce qui concerne l'irritation provoquée par les produits de soin (sans rinçage). MÉTHODES/RÉSULTATS: Un certain nombre de formulations cosmétiques différentes ont été évaluées dans les deux tests. Bien que les résultats du test épicutané n'indiquent pas de potentiels d'irritation substantiels, des réactions de type immédiat (picotements et rougeurs) ont été observées chez certains volontaires. Celles-ci ont disparu en à peu près 1 heure. Bien que transitoires, ces réactions de type 5 suggéraient que l'acceptation du consommateur serait probablement faible et les études ont été interrompues. Les réactions de type immédiat 6 sont rares mais ont été évoquées en relation avec certaines substances utilisées en cosmétique. Ces résultats inattendus étaient néanmoins intrigants et ont incité le lancement d’un processus pour voir si les protocoles de test épicutané pouvaient être modifiés pour évaluer ces réactions. Un protocole de test épicutané à court terme occlusif avec une période d'application de 20 min a été développé, permettant l'identification réussie des réactions spontanées. Il a été de plus constate une corrélation entre l'intensité des réactions observées dans le test épicutané à court terme et celles observées dans les test d’usage contrôlés. Le test épicutané à court terme utilisant le protocole développé peut donc être utilisé de manière fiable comme méthode de dépistage, par exemple dans le développement et l'optimisation de formulations cosmétiques contenant des ingrédients qui pourraient provoquer des réactions spontanées, par exemple de type urticaire de contact non immunologique.Les leçons tirées de ces études indiquent que de simples modifications des protocoles de test existants peuvent révéler des informations importantes sur les réactions cutanées. Ces modifications peuvent ensuite être utilisées pour créer d'autres blocs de construction dans le développement et l'optimisation de stratégies de test pour des formulations cosmétiques qui offrent des conceptions d'études fiables pour les réactions possibles que les développeurs de produits peuvent rencontrer.

Background Extending the drug provocation test (DPT) period is recommended for patients with suspected nonimmediate beta-lactam antibiotic (BLA) allergy and negative DPT. No consensus has been reached regarding the duration of prolonged provocation. Objective We aimed to determine the negative predictive value (NPV) of the 5-day extended DPT. Methods Parents of patients with suspected nonimmediate mild cutaneous reactions with BLAs who had been subjected to 5-day DPT with culprit drugs were questioned by telephone interview about reexposure to the tested drug. Patients with reported reaction during reexposure were reevaluated. Skin tests and serum-specific immunoglobulin E (IgE) analysis were not performed before first DPT. Results A total of 355 patients had negative results in 5-day DPT. The median age at DPT was 4.2 years, and 52.9% were male. The families of 255 patients (72%) could be contacted. Of these 255 patients, 179 (70%) had used the same drug, and reactions were reported for 6 (3.4%) of those patients, who were subsequently reevaluated. Five of the 6 patients had DPT with amoxicillin-clavulanate and 1 with cefixime. When detailed history was taken, 2 of the 5 patients with amoxicillin-clavulanate reaction were found to have used the drug unintentionally after their reaction to reexposure and did not have any symptoms. One of the patients underwent allergy workup and tested negative, and the other 2 refused the test. The patient with reported cefixime reaction underwent repeated allergy workup and tested negative. Therefore, the NPV of 5-day prolonged DPT was 98.9%. Conclusion The 5-day prolonged DPT has high NPV and seems appropriate in duration for children with suspected nonimmediate-BLA allergy.

Background: Recent studies demonstrated that, in the past few years, the number of jellyfish species is increasing worldwide; this increase can be explained by environmental and climatic reasons. Contacts with jellyfish can cause acute and chronic effects, including allergic reactions. Although anaphylaxis caused by jellyfish is a rare event, repetitive stings during bathing as well as marine sports and job activities represent important risk factors that can increase the probability of sensitization. Recently, it was also pointed out the possibility of anaphylaxis caused by jellyfish ingestion. In these cases, the sensitization could also be related to previous stings. In cases in which there is no history of jellyfish contact or ingestion, it has been hypothesized that there is a sensitization to an unknown cross-reactive antigen. Objective: The purpose of this work was to collect and review published studies and cases of anaphylaxis associated with jellyfish. Methods: We performed a medical literature data base search, which included English language articles published until September 2019, by using the key words “jellyfish” associated with “anaphylaxis” or “anaphylactic shock.” Results: The results of our research showed that dangerous reactions can be caused both by contact and ingestion. Moreover, the latest changes in food habits, life style, and globalization could lead to a more frequent exposure to jellyfish both by contact and ingestion, and, consequently, to a higher probability of sensitization. Conclusion: Prospective studies and well-structured research are needed to better understand all the potential immunologic elements of jellyfish, to clarify its role in sensitization, and to avoid possible dangerous allergic reactions caused by cross-reactivity.

Wine, beer, liquor, and spirits are widely consumed in many cultures across the globe, and for some individuals, ingestion, cutaneous contact, or other exposure can lead to dermatologic findings. However, there currently exist no comprehensive reviews on alcohol-related dermatitis. Herein, we will provide an overview of alcohol-related dermatitis and contact urticaria, including the epidemiology and clinical manifestations, potential allergens found in alcoholic beverages, testing approaches, and strategies for allergen avoidance.

Aim To study cell‐mediated immunity in the feet of people with type 2 diabetes with polyneuropathy. Methods In a cohort comprising people with type 2 diabetes with polyneuropathy (n = 17) and without polyneuropathy (n = 12) and a healthy control group (n = 12) indurations due to delayed‐type hypersensitivity responses to intracutaneous Candida albicans antigen were determined in the foot and compared with those in the arm (an area relatively spared in diabetic polyneuropathy). The sizes of indurations on the foot were correlated with electromyographic measurements in the participants with diabetes. Results No differences were observed in the median size of indurations between the foot and arm in healthy controls and participants without polyneuropathy; in participants with polyneuropathy, induration sizes on the foot were smaller than on the arm: 0 (95% CI 0 to 1) vs 5 (95% CI 2 to 6) mm (P < 0.01). In participants with diabetes, larger indurations correlated with better nerve function (Spearman's rho 0.35 to 0.39). Conclusion Our findings suggest that diabetic peripheral polyneuropathy negatively affects cell‐mediated immunity in the foot. (Clinical Trials registry no.: NCT01370837), What's new? Local immune responses can be impaired as a result of neurological deficits.Diabetic peripheral neuropathy could negatively affect cell‐mediated immunity selectively in the foot, the site most frequently and severely affected by peripheral neuropathy.More severe impairment of cell‐mediated immunity correlates with worse peripheral nerve function as measured by electromyography.Our study is the first to suggest the presence of locally diminished cell‐mediated immunity in the foot in people with diabetic peripheral neuropathy.Impaired cellular immunity in the foot may explain the paucity of signs of inflammation in diabetic foot infections.

Fenbfen is used for pain, pyrexia and in the management of osteoarthritis, rheumatoid arthritis and other musculoskeletal disorders. The present research was planned to examine the immunomodulatory activity of fenbufen in different models of cell-mediated immunity (CMI) and humoral immunity (HI). The CMI was evaluated by delayed-type hypersensitivity (DTH) and cyclophosphamide-induced neutropenia assays while HI was appraised by hemagglutination (HA) assay by administering fenbufen at 2, 6 and 10 mg.kg-1 and azathioprine 40 mg.kg-1 (as standard therapy) to albino mice by intraperitoneal route. The ex vivo immunomodulatory action was determined by red blood cell (RBC) membrane stabilization and protein denaturation assays. The results showed that fenbufen treatment had significantly (p

Confirming drug imputability is an important step in the management of cutaneous adverse drug reactions (CADR). Re-challenge is inconvenient and in many cases life threatening. We review the literature on ideal patch testing technique for specific CADRs. Testing should be performed approximately 3 months after the resolution of the eruption using standard patch testing techniques. Commercially available patch test preparations are available for a minority of drugs, so in most cases, testing should be performed with the drug at various recommended concentrations and in different vehicles. Testing to all known excipients, such as dyes, vehicles and preservatives is also important. Immunosuppressive medications should be discontinued or down titrated to the lowest tolerable dose to decrease the risk of false negative reactions. We provide an overview of expert recommendations and extant evidence on the utility of patch testing for identifying the culprit drug in common CADRs and for specific drug or drug classes. Overall, there appears to be significant variability in the patch test positivity of different drugs, which is likely the result of factors intrinsic to the drug such as dermal absorption (as a function of lipophilicity and molecular size) and whether the drug itself or a downstream metabolite is implicated in the immune reaction. Drugs with high patch test positivity rates include beta-lactam antibiotics, aromatic anticonvulsants, phenytoin, and corticosteroids, among others. Patch testing positivity varies both as a function of the drug and type of CADR. The sum of the evidence suggests that patch testing in the setting of morbilliform eruptions, fixed drug eruption, acute generalized exanthematous pustulosis, and possibly also drug-induced hypersensitivity syndrome, photoallergic and eczematous reactions may be worthwhile, although utility of testing may vary on the specific drug in question for the eruption. It appears to be of limited utility and is not recommended in the setting of other complex CADR, such as SJS/TEN and leukocytoclastic vasculitis.