Cutaneous Allergy Research Articles

Updating the British Society for Cutaneous Allergy Facial Series to ensure accurate diagnosis of allergic contact dermatitis

Allergic contact dermatitis (ACD) is a localised form of dermatitis or eczema which occurs 48‐72 hours after a substance which causes allergy (an allergen) has been in contact with the skin. It affects 20% of people. ACD to cosmetics is widely reported, with facial eczema being the main presenting complaint.

Roxithromycin inhibits compound 48/80-induced pseudo-allergy via the MrgprX2 pathway both in vitro and in vivo

Roxithromycin (ROX) is a macrolide antibiotic with a variety of immunological effects. Mast cells (MCs) play a key role in host defense, mediating hypersensitivity and pseudo-allergic reactions. Mas-related G protein-coupled receptor X2 (MrgprX2) is the main receptor related to pseudo-allergy. In this study, we investigated the anti-pseudo-allergy effect of ROX and its underlying mechanism. The effects of ROX on passive cutaneous anaphylaxis (PCA) and active systemic allergy were examined, degranulation, Ca2+ influx, and cytokine release were studied in vivo and in vitro. Interactions between ROX and MrgprX2 protein were also detected through surface plasmon resonance. The PCA and active systemic allergy induced by compound 48/80 were inhibited by ROX. An intermolecular interaction was detected between the ROX and MrgprX2 protein. In conclusion, ROX could inhibit pseudo-allergic reactions, and this effect involves the Ca2+/PLC/IP3 pathway of MrgprX2. This study provides new insight into the anti-pseudo-allergy effects of ROX.

BLOODSHED TREATED SUCCESSFULLY IN A HOUSE OF VILLAINS: A CHALLENGING AND UNUSUAL CASE OF HEMOPTYSIS IN A PATIENT WITH CONNECTIVE TISSUE DISEASE- PULMONARY ARTERIAL HYPERTENSION

SESSION TITLE: Medical Student/Resident Chest Infections Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Pulmonary arterial hypertension (PAH) is a progressive disease caused by a remodeling of precapillary arterioles that leads to a progressive increase in pulmonary vascular resistance and right ventricular failure. PAH can complicate any connective tissue disease, most frequently SSc as discussed above, but also SLE, MCTD, RA, or other diseases such as Sjogren’s syndrome (SS) and dermatomysositis with often a poor prognosis. Our case illustrates a case of Hemoptysis under uniquely complex circumstances. CASE PRESENTATION: 53-year-old Hispanic female initially presented with features of severe Acute right heart failure, cardiogenic shock and Hypoxemia. Pulmonary arterial hypertension (PAH) diagnosis was made and was stabilized on emergent parenteral prostacyclin therapy. We also found connective tissue disease (CTD) with Sjogren’s features. She had history of recurrent Venous thromboembolism (VTE) and was on rivaroxaban. PAH therapy - SQ Treprostinil (@ 60ng/kg/min) + tadalafil 40mg qd. A few months later, she developed (CNPA). She responded well to voriconazole with clinical & radiographic improvement. A significant cutaneous allergic reaction to voriconazole led to its cessation and substitution with posaconazole. She presented with large volume hemoptysis with preceding minor episodes for several days. She was hemodynamically stable with no constitutional symptoms. CT chest revealed a stable appearing right upper lobe pulmonary mass measuring 5.5 x 3.0 cm. BNP was 67. Anticoagulation was held and an IVC filter was placed emergently. Bronchoscopy revealed necrotic debris, tan purulent mucous, and blood in the anterior segment of the right upper lobe. Interventional radiology performed bronchial and subclavian angiography with chemoembolization (small branch of the right subclavian artery & the distal portion of the right bronchial artery) of the Aspergilloma. Anticoagulation was resumed after with no further episodes of hemoptysis and she was successfully discharged. DISCUSSION: In a review of patients with SS & PAH, the mean age at diagnosis of PAH was 50 and all female with severe functional class (FC III and IV) and hemodynamic impairment (1), strikingly similar to our case. Survival rate was low (66% at 3 years) as standard therapy of PAH was typically ineffective despite an initial improvement. However, Significant clinical improvement was noted in our patient with Parenteral prostacyclin therapy and PDE5 inhibitors. CONCLUSIONS: This case illustrates a complex unique clinical situation that was challenging – Hemoptysis from CNPA with a background of the following active diagnoses: PAH, CTD (Sjogren’s features), Recurrent VTE. Chemoembolization of feeding arteries + IVC filter placement + temporary cessation of anticoagulation was used with a successful outcome. Reference #1: Sato T, Hatano M, Iwasaki Y, et al. Prevalence of primary Sjögren's syndrome in patients undergoing evaluation for pulmonary arterial hypertension. PLoS One. 2018;13(5):e0197297. Published 2018 May 15. doi:10.1371/journal.pone.0197297 DISCLOSURES: Clinical Research - PI relationship with United Therapeutics Please note: 3 years Added 05/08/2020 by Vijay Balasubramanian, source=Web Response, value=Grant/Research Support Speaker relationship with Bayer Please note: 3 years Added 05/08/2020 by Vijay Balasubramanian, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: $1001 - $5000 Added 05/08/2020 by Vijay Balasubramanian, source=Web Response, value=Honoraria No relevant relationships by Eric Reid, source=Web Response No relevant relationships by James Yang, source=Web Response

The Last Three Decades of Contact Dermatitis

Background Contact dermatitis is a common inflammatory skin disease, and it affects approximately 20% of the adult population. Bibliometrics is a statistical analysis of academic literature in a certain field. Although bibliometric studies have been popular in recent years, the literature has limited number of bibliometric researches focusing on dermatology. Objective We aimed to perform the first bibliometric analysis of contact dermatitis literature. Methods All data of our study were obtained from the databases provided by Web of Science. We used the keywords “contact dermatitis,” “irritant contact dermatitis,” “allergic contact dermatitis,” “cutaneous allergy,” “occupational dermatitis,” and “patch test” for our search. All items published between 1988 and 2017 were included. Results A total of 37,283 documents were found. The most studied research areas were dermatology, immunology, and allergy (79.7%, 65.02%, and 58.6%, respectively). The peak year of contact dermatitis literature was 2011 with 1,782 items. The United States covered 24.77% of contact dermatitis literature with 9,237 documents. Germany, the United Kingdom, Japan, and France followed the United States (n = 4,121, 3,420, 2,870, and 2,627 items, respectively). Denmark was the most productive country, followed by Sweden, Finland, Switzerland, and Belgium. Conclusion Physicians from developing and least developed countries should be supported to perform novel bibliometric researches on contact dermatitis.

British Society for Cutaneous Allergy

British Society for Cutaneous Allergy

Acute and subacute oral administration of mycotoxin deoxynivalenol exacerbates the pro-inflammatory and pro-pruritic responses in a mouse model of allergic dermatitis.

Deoxynivalenol (DON) contamination in food is a public health concern; however, the effect of DON exposure on immune disorders including allergies remains unclear. The aim of this study is to elucidate the effect of oral exposure to DON on pro-inflammatory and pro-pruritic responses in a mouse model of allergic dermatitis, which was generated by topical application of toluene-2,4-diisocyanate (TDI), a hapten that induces type-2 helper T cells. To evaluate acute exposure to DON, the mice were orally administered vehicle alone, 0.1mg/kg DON, or 0.3mg/kg DON 48, 24, and 1h before the final challenge with TDI. To study subacute exposure, the mice were fed DON-contaminated rodent diet (0.3ppm) during the experimental period. After the itch behavior and ear-swelling response were monitored, the serum, auricular lymph node, and skin tissue were collected for analyzing immunocyte differentiation, cytokine determination, and histological changes. Acute oral administration of DON significantly enhanced pro-inflammatory responses including ear-swelling response, immunocyte infiltration, and cytokine productions. Histological evaluation supported the occurrence of pro-inflammatory responses. In contrast, acute DON exposure only slightly increased itch behavior. Subacute oral exposure to DON significantly up-regulated the inflammatory responses, but showed almost no effect on pruritic response. In vitro evaluation in dendritic cells and keratinocytes indicated that DON pre-exposure induced a dose-dependent significant increase in cytokine production. Our results imply that both acute and subacute exposures to DON are associated with pro-inflammatory responses in cutaneous allergy.

Activation of aryl hydrocarbon receptor by benzo[a]pyrene increases interleukin 33 expression and eosinophil infiltration in a mouse model of allergic airway inflammation.

We recently demonstrated that benzo[a]pyrene (BaP), the aryl hydrocarbon receptor (AhR) ligand, directly contributes to aggravation of cutaneous allergy in a mouse model of allergic dermatitis. The present study aimed to determine whether BaP-induced AhR activation results in development of airway inflammation. Initially, the potential for a direct relationship between BaP-induced AhR activation and airway inflammation was investigated in vivo, using a mouse model of type 2 helper T cell (Th2) hapten toluene-2,4-diisocyanate (TDI)-induced airway inflammation. Mice were orally administered BaP at 48, 24, and 4 h before the final allergen challenge. Oral administration of BaP showed a significant increase in lung inflammation and eosinophil infiltration. While expression of Th2 cytokines such as interleukin 4 (IL-4) and IL-13 was not affected by exposure to BaP, AhR activation significantly increased IL-33 expression. To confirm the in vivo results, in vitro experiments were performed using the human eosinophilic leukemia cell line (EOL-1), human bronchial epithelial cell line (BEAS-2B), and human lung adenocarcinoma epithelial cell line (A549). Results indicated that pre-treatment with BaP increased expression of IL-8 in house dust mite-activated EOL-1, BEAS-2B, and A549 cells. In addition, IL-33 levels in BEAS-2B cells were significantly increased after BaP exposure. Our findings indicated that BaP-induced AhR activation is involved in the pro-inflammatory response in respiratory allergy, and that this effect may be mediated by increased IL-33 expression and eosinophil infiltration.

What is in? What is out? Updating the British Society for Cutaneous Allergy facial series.

Allergic contact dermatitis (ACD) to cosmetics is widely reported. To ensure we are accurately diagnosing ACD, patch test series should be continually reviewed to identify relevant and emerging allergens and highlight those that are outdated. The current British Society for Cutaneous Allergy (BSCA) facial series recommends 26 allergens and was last modified in 2012. To review and update the BSCA facial series. We retrospectively reviewed the results from 12 UK and Ireland patch test centres' facial series from January 2016 to December 2017. We recorded the number of allergens tested in each centre and the detection rate for each allergen. Using a 0·3% positive rate as the inclusion threshold, we established which allergens in the BSCA facial series had positive patch test rates < 0·3% and > 0·3%. Allergens not in the BSCA facial series that had a positive patch test rate > 0·3% were identified. Overall, 4224 patients were patch tested to the facial series. The number of allergens included in individual centres' facial series ranged from 24 to 66, with a total of 103 allergens tested across all centres. Twelve of the 26 allergens in the BSCA facial series had a positive patch test rate < 0·3% and 14 had a rate > 0·3%. Twenty-five allergens not recommended in the BSCA facial series had a positive patch test rate > 0·3%. This audit has highlighted the significant variation in practice that exists among patch test centres, despite a recommended facial series. The BSCA facial series has been updated and now contains 24 allergens. Fifteen allergens remain, 11 allergens have been dropped and nine new allergens have been added.

Prevalence of metal hypersensitivity in patients with shoulder pathologies

To date, medical history and dedicated questionnaires are the fastest and easiest way to assess risks of joint metal hypersensitivity. No published studies determined the overall prevalence of hypersensitivity to metals in patients with shoulder pathologies. The purpose of this study was therefore to estimate the prevalence of metal hypersensitivity reported by patients with shoulder pathologies, and to identify patients at risk of joint metal hypersensitivity based on a dedicated questionnaire. The authors prospectively asked all adult patients consulting for shoulder pathologies between September 2018 and February 2019 at 10 centers to fill in a form. The main outcome was "reported hypersensitivity to metals,"comprising belt buckles, coins, earrings, fancy jewelry, keys, leather, metallic buttons, piercings, spectacles, watch bracelets, or zips. A total of 3217 patients agreed to fill in the survey, aged 55 ± 16 (range, 18-101) with equal proportions of men (51%) and women (49%), and a majority of patients consulting for cuff pathology (55%). A total of 891 (28%) patients had professions considered at risk formetal hypersensitivity. The most frequently reported metal hypersensitivities were fancy jewelry (15%), earrings (13%), and watch bracelets (9%). A total of 629 (20%) patients, of which the vast majority were women, reported hypersensitivity to 1 or more metals. This survey of 3217 patients identified 20% who reported metal hypersensitivities, though only 2.2% had done patch tests. Matching profiles of those with positive patch tests to those with no patch tests revealed that 9.4% of the total cohort had similar sex and self-reported metal hypersensitivities. Factors associated with a positive patch test were female sex, self-reported cutaneous allergy, and self-reported metal hypersensitivity. The clinical applicability of these estimates remains uncertain as there is insufficient evidence that allergy to metal implants can be predicted by questionnaires or patch tests.

Electroacupuncture improves cutaneous allergic reaction by inhibiting degranulation of intrape-ritoneal mast cells, MAPK signaling and inflammatory factor levels in urticaria rats

To observe the effect of electroacupuncture (EA) on degranulation of intraperitoneal mast cells (MCs) and expression of mitogen-activated protein kinase (MAPK) signaling related proteins, tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6) in urticaria rats, so as to reveal its mechanisms underlying improvement of urticaria. Thirty-two SD rats were randomly divided into control，model，EA and medication groups (n＝8 in each group). The urticaria model was established by using passive cutaneous anaphylaxis (PCA) reaction method. EA (2 Hz /15 Hz, 1 mA) was applied to bilateral "Zusanli"(ST36), "Quchi "(LI11) and "Xuehai"(SP10) for 20 min，once daily for 7 consecutive days before antigen attack. Rats of the medication group were treated by gavage of Loratadine(1 mg•kg－1•d－1)for 7 days. The diameter of cutaneous Evan's blue spots was measured to evaluate the severity of PCA. Intraperitoneal fluid smears were prepared to observe the degranulation state of MCs. The contents of TNF-α and IL-6 in the intraperitoneal fluid were detected by ELISA, and the expression of extracellular signal-regulated kinase (ERK), phosphorylated (p)-ERK, c-Jun N-terminal kinase (JNK), p-JNK, P38MAPK and p-P38MAPK of the acquired intraperitoneal MCs was detected by Western blot. The diameter of cutaneous Evan's blue spot was significantly increased in the model group than that in the control group (P<0.01), and considerably decreased in both EA and medication groups compared with the model group(P<0.01). After modeling，the percentage of degranulated MCs, contents of TNF-α and IL-6, and expression levels of ERK, p-ERK, JNK, p-JNK, P38MAPK and p-P38MAPK were remarkably increased in the mo-del group than those in the control group (P<0.01, P<0.05). After the treatment, the percentage of degranulated MCs, contents of TNF-α and IL-6, and expression levels of p-ERK, JNK, p-JNK and p-P38MAPK were obviously decreased in both EA and medication groups relevant to the model group (P<0.01, P<0.05), while no significant changes were found in the expression of ERK in both EA and medication groups, and P38MAPK in the EA group. Compared with the model and EA groups, expression levels of P38MAPK were down-regulated in the medication group (P<0.05). EA can reduce skin allergic reaction in rats with urticaria, which may be related to its effects in inhibiting the degranulation of intraperitoneal MCs, down-regulating the expression of MAPK signaling-related proteins and the level of pro-inflammatory factors TNF-α and IL-6 in intraperitoneal MCs.

Allergic and photoallergic contact dermatitis to chlorpromazine.

Chlorpromazine is known to produce both systemic phototoxic and photoallergic reactions. However, it may also cause photoallergic contact dermatitis and, albeit exceptionally, allergic contact dermatitis (ACD). We present a series of photoallergic contact dermatitis and ACD to chlorpromazine diagnosed at a tertiary centre cutaneous allergy unit between 1980 and 2019.

Effect of diphenhydramine and cetirizine on immediate and late-phase cutaneous allergic reactions in healthy dogs: a randomized, double-blinded crossover study.

Currently, there is insufficient evidence to confirm oral diphenhydramine (DPH) efficacy to prevent mast cell degranulation and histamine release in dogs. To determine and compare the effects oral of DPH and cetirizine on the immediate- and late-phase cutaneous allergic reactions in healthy dogs. Twelve healthy laboratory beagle dogs. The study was designed as a randomized, double-blinded crossover study in which each dog served as its own control; twice-daily oral DPH (2.2mg/kg) or cetirizine (2mg/kg) were given for six days with a two week washout period. Intradermal injections of histamine, compound 48/80 (positive control) and saline (negative control) were performed on the right thorax 10days before drug administration (baseline), during oral antihistamine administration on Day 6 and 10days after last medication dosage. Global wheal scores (GWS) at 20min and late-phase reactions (LPR) at 6h post-injection were evaluated by an investigator blinded to the drug and the interventions. Treatment with cetirizine significantly reduced histamine and compound 48/80 GWS and LPR compared to baseline; there was no significant difference for DPH. In all dogs, oral DPH and cetirizine reached plasma concentrations considered therapeutic in people. No adverse effect or behavioural changes were observed during the study. In conclusion, oral cetirizine was effective in preventing cutaneous allergic reactions without any obvious adverse effects in dogs. Oral DPH failed to show an inhibitory effect despite attaining plasma drug concentrations that are considered effective in people.

Diagnostic Approach for Suspected Allergic Cutaneous Reaction to a Permanent Tattoo.

The last few decades have seen a notable increase in the number of people who have a tattoo. This practice is not free from complications. Most adverse effects appear early and are temporary, although they can occasionally develop later and be permanent and serious. Recent research has generated new knowledge on the composition of inks, their degradation over time, the immune activity that is stimulated, and the various clinical disorders that can arise. This information enables better approaches to diagnosis and management when complications arise. Diagnosing allergic reactions to permanent tattoo ink can be very challenging. This review aims to identify clinical and histological clues to help practitioners differentiate allergic reactions from other complications. We discuss the yield and appropriateness of skin tests and biopsies and propose an algorithm to guide the diagnostic process.

Trend of relevant contact allergens of the feet in Spain over a period of 10 years.

Allergic contact dermatitis (ACD) of the feet accounts for approximately 10% of all patch tested patients. To study the clinical profile of patients with feet dermatitis and relevant contact allergens in Spain over a 10-year period. Retrospective observational study of patients with suspected ACD from the GEIDAC (Spanish Research Group on Contact Dermatitis and Cutaneous Allergy) baseline series from eight hospitals in Spain between 2004 and 2014. The clinical data collected from each patient were age, sex, occupation, history of atopic dermatitis, and eczema location. A total of 450 cases clinically presented dermatitis affecting the feet; of these, 41% of were males and 5.6% were suspected to be of occupational origin. As much as 47% were diagnosed with ACD, 20% with atopic dermatitis/dyshidrotic eczema, and 5% with psoriasis. The "feet group" included statistically significantly more females in the age range of 21 to 60 years. The most frequent relevant contact allergens were potassium dichromate, cobalt(II) chloride, p-tert-butylphenol formaldehyde resin, mercapto mix, and mercaptobenzothiazole. ACD is the most frequent clinical diagnosis of feet dermatitis in our series. The most frequent allergens are similar to those published in other series of foot ACD in Europe and the trend has not changed in the studied decade.

The effect of anti-inflammatory and anti-oxidant diet on immediate and late-phase cutaneous allergic reactions in healthy dogs

The effect of anti-inflammatory and anti-oxidant diet on immediate and late-phase cutaneous allergic reactions in healthy dogs

Eyelid dermatitis. Experience in our Cutaneous Allergy Unit between 1980 and 2018.

Eyelid dermatitis. Experience in our Cutaneous Allergy Unit between 1980 and 2018.

Quantification of cutaneous allergic reactions using 3D optical imaging: A feasibility study

BackgroundUser‐independent quantitative measures of cutaneous allergic reactions can help the physicians manage and evaluate the treatment of cutaneous allergic reactions. In this paper, we present and validate a method to quantify the elevation, volume and area of cutaneous allergic reactions to red tattoos.MethodsThe skin surface of allergic tattoo reactions was imaged using an optical 3D scanner. The in‐house developed analysis tool measured the elevation, volume and area of the lesions, compared to a reference surface. This reference surface was created by 3D interpolation of the skin after manual removal of the lesions. The error of the interpolation tool was validated using a digital arm model. The error of our optical scanner was determined using a 3D printed lesion phantom. The clinical feasibility of the method was tested in 83 lesions in 17 patients.ResultsThe method showed clear potential to assess skin elevation, volume change and area of an allergic reaction. The validation measurements revealed that the error due to interpolation increases for larger interpolation areas and largely determined the error in the clinical measurements. Lesions with a width ≥4 mm and an elevation ≥0.4 mm could be measured with an error below 26%. Patient measurements showed that lesions up to 600 mm2 could be measured accurately, and elevation and volume changes could be assessed at follow‐up.ConclusionQuantification of cutaneous allergic reactions to red tattoos using 3D optical scanning is feasible and may objectify skin elevation and improve management of the allergic reaction.

Genomic Regions Associated with IgE Levels against Culicoides spp. Antigens in Three Horse Breeds.

Insect bite hypersensitivity (IBH), which is a cutaneous allergic reaction to antigens from Culicoides spp., is the most prevalent skin disorder in horses. Misdiagnosis is possible, as IBH is usually diagnosed based on clinical signs. Our study is the first to employ IgE levels against several recombinant Culicoides spp. allergens as an objective, independent, and quantitative phenotype to improve the power to detect genetic variants that underlie IBH. Genotypes of 200 Shetland ponies, 127 Icelandic horses, and 223 Belgian Warmblood horses were analyzed while using a mixed model approach. No single-nucleotide polymorphism (SNP) passed the Bonferroni corrected significance threshold, but several regions were identified within and across breeds, which confirmed previously identified regions of interest and, in addition, identifying new regions of interest. Allergen-specific IgE levels are a continuous and objective phenotype that allow for more powerful analyses when compared to a case-control set-up, as more significant associations were obtained. However, the use of a higher density array seems necessary to fully employ the use of IgE levels as a phenotype. While these results still require validation in a large independent dataset, the use of allergen-specific IgE levels showed value as an objective and continuous phenotype that can deepen our understanding of the biology underlying IBH.

Cutaneous Allergy

A new Annals feature in 2018, "From the Pages of AllergyWatch" is devoted to publishing synopses of Allergy and Asthma literature relevant to a topic of emphasis. These unbiased synopses and comments by our Editors have been previously printed in the AllergyWatch bimonthly newsletter, and it is our hope that presenting carefully selected article summaries and comments in the Annals will serve as a valuable educational resource for practicing allergists.

Levodopa-induced skin disorders in patients with Parkinson disease: a systematic literature review approach.

The use of levodopa for treatment of Parkinson's disease is a well-established clinical practice. Data about the true incidence and severity of cutaneous complications associated with the use of levodopa are largely lacking. Aim of this review was to evaluate the quality of evidence referring to the skin disorders caused by levodopa treatment for Parkinson's disease. Thirty of 1084 studies were included; 8 randomized controlled trials and 22 case reports in a total of 2749 patients. Malignant melanoma was the most frequent oral levodopa-related skin disorder followed by allergic cutaneous reactions, alopecia, vitiligo, skin hyperpigmentation, Laugier-Hunziker syndrome, Henoch-Schönlein syndrome, pseudobullous morphea and scleroderma-like illness. Naranjo scores ranged from 2 to 8. Regarding levodopa clinical trials, the most frequent skin complication was peripheral edema, followed by malignant melanoma. Although evidence is not robust, melanoma is the most frequent and possible fatal levodopa-associated skin disorder, while other skin allergic or immunological reactions are less common and reversible. Although levodopa treatment may induce melanogenesis and promote melanomagenesis, existing evidence does not support an association between levodopa therapy and induction or progression of malignant melanoma. The suggested association with melanoma may reflect the well-documented association of Parkinson's disease with melanoma rather than the exposure to the drug. Nevertheless, until a solid conclusion can be drawn, the use of levodopa in the context of malignant melanoma should be considered with caution. Well-designed prospective studies are needed to determine the cause and effect relationship between levodopa and skin disorders.