Diagnostic Patch Testing Research Articles

Less efficient skin penetration of the metal allergen Pd2+ compared to Ni2+ and Co2+ from patch test preparations.

Contrary to Ni2+- and Co2+-induced allergic contact dermatitis (ACD), reactions against Pd2+ are rare. However, Pd2+ activates a larger T cell fraction in vitro, suggesting an inefficient skin penetration. This study compares Ni2+, Co2+ and Pd2+ skin penetration from commonly used diagnostic patch test preparations (PTPs) and aqueous metal salt solutions. Using Franz diffusion cell assays, we applied the metals in PTPs (5% NiSO4, 1% CoCl2, 2% PdCl2 and 3% Na2PdCl4) and in solution to pigskin for 48 h, thereby mirroring the time frame of a patch test. The different compartments were analysed individually by inductively coupled plasma mass spectrometry. Metal ions were mainly retained in the upper stratum corneum layers. After application of PTPs, concentrations in the viable skin were lower for Pd2+ (1 and 7 μM) compared to Ni2+ and Co2+ (54 and 17 μM). Ni2+ and Co2+ penetrated the skin more efficiently than Pd2+ and thus may sensitize and elicit ACD more easily. This was observed for ions applied in petrolatum and aqueous solutions. We hypothesize that the differently charged metal complexes are responsible for the varying skin penetration behaviours.

Nickel Challenge In Vitro Affects CD38 and HLA-DR Expression in T Cell Subpopulations from the Blood of Patients with Nickel Allergy.

Nickel allergy is a major health problem and shows clinical manifestation of contact eczema. The response of specific lymphocyte subpopulations in sensitized patients after new challenge to nickel has until now not been studied in detail. To evaluate if nickel-based elicitation reaction could be objectively identified by multi-parametric flow cytometry, immunophenotyping of specific T cells was applied. White blood cells from 7 patients (4 positive in patch test, 3 negative) were challenged by nickel and in vitro short-term culture. Standardized antibody-dye combinations, specific for T helper(h)1, Th17 and cytotoxic T cell activation, were selected according to the recommendations of Stanford Human Immune Monitoring Center. In cytotoxic CD8+CCR7+CD45RA+ T cells from patients suffering from nickel allergy, CD38 and HLA-DR were elevated comparing to healthy donors. After challenge to nickel in vitro both markers decreased in CD8+CCR7+CD45RA+ T cells but found up-regulated in CD4+CCR7+CD45RA+CCR6-CXCR3+Th1 cells. Intracellular expression of T-bet and RORγt further indicated Th1 and Th17 cells. Finally, CD4+CD25+CCR4- T cells increased after challenge with nickel in PBMCs of patients with nickel allergy. Flow cytometry based quantification of T cell markers might be used as a specific and reliable method to detect chemical induced skin sensitization and confirm diagnostic patch testing in the clinics.

CD01 Sodium benzoate: an important allergen to patch test to — is 5% in petrolatum too irritant?

Abstract Sodium benzoate is a naturally occurring preservative present in substances including cinnamon and apples. It is used as a food preservative and increasingly in leave-on and wash-off personal care products (PCPs), including moisturizers, hand washes, shampoos, mouthwash, toothpaste and baby wipes. Increased use results, in part, from European Union legislation regulating other preservatives, notably methylchloroisothiazolinone and methylisothiazolinone, which are banned in leave-on PCPs and are required to be used in reduced concentrations in wash-off products. Sodium benzoate was recently recommended for consideration for inclusion in the British Society for Cutaneous Allergy facial series after a national audit demonstrated that 1.5% of patients tested positive on patch testing when tested to sodium benzoate 5% in petrolatum (pet.) (Rolls S, Owen E, Bertram CG et al. What is in? What is out? Updating the British Society for Cutaneous Allergy facial series. Br J Dermatol 2021; 184:151–5). In our institution, 3229 patients were patch tested to sodium benzoate 5% in pet. from Chemotechnique Diagnostics™ from 2008 to 2022. It was tested in targeted series, bakery and cheilitis (2008–2022), and variably in fragrance (2012–2018) and cosmetic (2015–2018 and 2021–2022) series. We noted many irritant reactions to sodium benzoate 5% pet. and undertook an audit. Fifty-seven (1.8%) patients had positive reactions (+/++), 52 (1.6%) had doubtful reactions (? +), and 133 (4.1%) had irritant reactions. Of the positive reactions, 38 (66.7%) were of current relevance and 19 (33.3%) were of unknown relevance. The frequency of positive (+/++) reactions in the different targeted series was as follows: bakery and cheilitis 1.5%, cosmetic 1.7% and fragrance 2.1%. Concerningly, over three times more patients had irritant or doubtful reactions (5.7%) than those who tested positive (1.8%). When concentrations of a patch test preparation are decreased, the rate of irritancy on patch testing usually also decreases (Johansen J, Aalto-Korte K, Agner T et al. European Society of Contact Dermatitis guideline for diagnostic patch testing – recommendations on best practice. Contact Dermatitis 2015; 73:195–221). Given that sodium benzoate is a known allergen with increasing frequency of use, it is important that the optimum concentration and vehicle are used for patch testing to ensure adequate sensitivity but low irritancy. Decreasing the patch test concentration of sodium benzoate to 2% in pet., which is commercially available, may reduce irritant reactions and the risk of false positives. We recommend that dilutional studies should be performed comparing 5% with 2% in pet. with the hope that the latter is comparatively a nonirritant preparation without loss of sensitivity.

CD13 Remote review for final patch test reading: a virtual reality?

Abstract Patch test reading at day 7 is suggested in current national (British Association of Dermatologists 2017) and international (European Society of Contact Dermatitis 2015) guidelines to identify late positive reactions. Allergens most established with late reactions are metals, antibiotics, acrylates and preservatives (Viggiano T, Yiannias JA, Yang YW. A retrospective review of late delayed positive patch testing greater than day 8 at Mayo Clinic from 2001 to 2020. Dermatitis 2022; 33:411–16). We report a case of significantly delayed contact dermatitis to four acrylates and ethyl paraben in a 49-year-old immunocompetent woman. She was referred to the cutaneous allergy clinic for patch testing following a rash affecting the torso after application of a sunscreen during a sunny holiday. She reported historical skin irritation after the use of nail lacquer and at the site of a caesarean section wound that was closed with skin glue 14 years prior. Patch test reading at day 4 (96 h) was negative; positive reactions to ethyl paraben, 2-hydroxyethylmethacrylate and ethyl cyanoacrylate appeared at day 23 (552 h). Positive reactions to hexanediol diacrylate and triethylene glycol diacrylate appeared at day 31 (744 h). These were communicated to us by the patient via email, with photographs clearly showing the development of new positive reactions. Of note, there was no reaction to the sunscreen product, although ethyl paraben was identified in the ingredients list, as well as two acrylate-containing polymers. Sensitization from diagnostic patch testing carried out to accepted international guidelines is rare but can occur with some allergens such as strong sensitizers, including paraphenylenediamine. The allergens identified in our case are found commonly in everyday cosmetics, adhesives and preservatives, including some that the patient had identified previous exposure to. Acrylates are acknowledged for causing potential delayed positive reaction by day 8 (Viggiano et al.); one case report describes true allergic acrylate reaction in a dental worker after 5 weeks (Fowler JF Jr. Late patch test reaction to acrylates in a dental worker. Am J Contact Dermat 1999; 10:224–5). There are no established reports of late positive reactions to ethyl paraben. With increasing online resources, delayed reactions beyond day 7 can be established with patient-initiated remote review of photographs taken during and subsequent to patch testing appointments. This case highlights the importance of keeping channels open for patients to contact the cutaneous allergy team after the final in-person reading to ensure (very) late allergen reactions are not missed.

Risk management of skin sensitisers: A commentary

Historically, allergic contact dermatitis (ACD) to chemicals encouraged hazard identification improvements, more sophisticated risk assessment and implementation of regulatory strategies, including banning of specific sensitising substances. The validation process applied to hazard identification methods demonstrates their accuracy; their use to characterise sensitiser potency facilitates quantitative and transparent risk assessment. Diagnostic patch testing at dermatology clinics worldwide delivers feedback showing where risk assessment/management has been insufficient or did not target the exposure of concern, thereby facilitating improvements. When urgent action to protect human health was required, regulations limited/banned, specific skin sensitisers. This can be seen in practice with the fragrance industry, a known source of ACD, thus requiring risk management, usually restrictions to limit allergy induction, and very rarely specific bans on ingredients. Experience and development of more sophisticated tools, e.g. to assess aggregate exposure from multitude of consumer product types, has led to repeated adaptation of risk assessment and promulgation of updated fragrance use limits. Although targeted control may not always lead to rapid change in the overall clinical picture, it is preferable to a blanket undifferentiated regulatory control of all sensitisers, resulting in unwarranted restrictions for many uses of no health concern, with consequent substantial socio-economic impacts.

THE "FLARE-UP PHENOMENON": NEW ONSET OF DISTANT DERMATITIS DURING PATCH TESTING

<h3>Introduction</h3> Allergic contact dermatitis is common, affecting ∼20% of adults, and is often evaluated via diagnostic patch testing.[1] In rare cases, patch testing may result in worsening of pre-existing dermatitis, but development of de novo lesions is unusual.[2] <h3>Case Description</h3> In 2018, a 46-year-old woman experienced severe, bilateral eyelid swelling with intense itching and skin cracking, along with an eczematous rash on her chest and hands. Inpatient workup revealed no infectious/rheumatologic cause, and patient was diagnosed with contact dermatitis from an unknown trigger. After a period of remission, in 2021 patient again developed bilateral eyelid rash without involvement of the hands or chest. Following treatment with topical steroids, eyelid rash resolved. Epicutaneous patch testing was performed (T.R.U.E. TEST). 36h after patch test placement, patient experienced, rapid intensification of eczematous lesions around the eyelids, as well as new onset of rash on the dorsa of her hands, which had been unaffected prior to patch testing (Figure 1). 72h read was positive to colophony and fragrance mix (+1). Systemic and topical corticosteroids were prescribed for presumed flare-up phenomenon, with subsequent resolution of periorbital and hand rash. <h3>Discussion</h3> While generally well-tolerated, diagnostic patch testing has been associated with the "flare-up" phenomenon, worsening pre-existing eczema—and, in this case, leading to the development of de novo lesions.[3] Flare-up is more common in polysensitized patients, as was seen in our case.[2] The mechanism of the "flare-up phenomenon" is poorly understood, but is believed to involve reactivation of memory T cells at previous sites of disease.[3]

Nickel hypersensitivity and endovascular devices: a systematic review and meta-analysis

ObjectiveNickel allergy is common; endovascular specialists are often confronted with nickel allergic patients ahead of the implantation of endovascular devices, many of which are nickel-containing. Our aim was to elucidate...

Epicutaneous Patch Testing in Type IV Allergy Diagnostics: State of the Art and Best Practice Recommendations.

This chapter summarises all relevant aspects of patch testing, closely following recommendations outlined in a recent European, and a German S3 guideline on diagnostic patch testing with contact allergens and medicinal products (drugs). Patch testing is indicated in patients suspected of suffering, or having been suffering, from delayed-type hypersensitivity leading to allergic contact dermatitis or other skin and mucosal diseases. Sections of this chapter include detailed indications, reasons for possibly postponing the test, considerations on choosing haptens (contact allergens) to test, various aspects of the application of patch test allergen preparations (storage, dosing) and of testing with individual materials provided by the patients. Special aspects of patch testing in cutaneous adverse drug reactions, children, or occupational contact dermatitis are outlined. Supplemental test methods, notably the repeated open application test, are briefly described. Finally, the final evaluation in terms of assessment of clinical relevance of reactions and patient counselling are outlined.

Allergic Contact Dermatitis to Components of Wearable Adhesive Health Devices.

Consumer use of wearable health devices has been rapidly increasing. Because of prolonged skin contact required, allergic contact dermatitis to components has been reported. Eczematous rash is the most common dermatologic adverse reaction to continuous glucose monitors, and rash from wearable activity trackers is commonly reported by consumers, suggesting that allergic contact dermatitis to wearable health devices may be vastly underreported. Acrylates, methacrylates, and colophonium are the most common allergens found on patch testing. Isobornyl acrylate has been identified as the primary allergen in many cases of allergic contact dermatitis to continuous glucose monitors. These chemicals are found in either the adhesives or the units themselves. Awareness of the presence of these chemicals in wearable devices may provide assistance for diagnostic patch testing in users who have dermatological reactions to the devices and hopefully guide dermatotoxicological evaluation guidance by government and industry.

Addressing the conundrums of p-phenylenediamine hair dye allergy by applying Friedmann's principles of contact sensitization.

In the first conundrum, permanent hair dyeing involves the use of aromatic amines such as p-phenylenediamine (PPD), whose oxidation is pivotal to the dyeing process, but also generates potent allergens. Despite prolonged efforts by industry to search for safer alternatives, hair dyeing is still reliant on this type of aromatic amine. In the second conundrum, patch testing with 1% PPD remains the most useful screen for hair dye contact allergy. However, there is a very small but real risk of actively sensitizing the patient. Lowering the PPD concentration below 1% significantly reduces test sensitivity and diagnostic utility. Here, we argue that by applying Friedmann's principles of contact sensitization each conundrum can be addressed from a new perspective. These principles indicate that, when the exposed area of skin is small (<1 cm2 ), induction of contact allergy is sharply reduced, whereas elicitation of allergy is unaffected. Careful reflection on this principle suggests that we can predict where hair dye sensitization is most likely to occur, indicates a strategy to reduce the chance of contact sensitization occurring in consumers as a result of hair dyeing, and how we might mitigate the risk of active sensitization resulting from diagnostic patch testing.

A diagnostic checklist for generalized dermatitis.

PurposeGeneralized dermatitis (defined as histological spongiotic dermatitis affecting more than three anatomical areas of the skin surface) has many potential causes that mimic atopic dermatitis and contact dermatitis. If a treatable cause is missed, the patient may be treated with chronic immunosuppressive therapy that carries more risk than specific treatment for a disease mimicking dermatitis. Checklists have been shown to improve patient safety, primarily in procedural contexts. This work assessed the utility of a diagnostic checklist for subacute and chronic generalized dermatitis in patients who had not improved after at least 1 month of avoidance of contact allergens identified by comprehensive patch testing, if indicated.Patients and methodsDesigned as a quality improvement project using Standards for Quality Improvement Reporting Excellence (SQUIRE) guidelines, a diagnostic checklist was used by the principal investigator for 1 year in a tertiary referral dermatitis clinic for patients without a confirmed cause for the dermatitis after two to three visits with the investigator. All patients had had diagnostic patch testing if indicated. Almost all had undergone skin biopsy by their referring provider. Fifteen patients met the criteria for inclusion in this study. Outcome measures included provider and patient perception of efficiency and/or confusion caused by the checklist. Length of time from the initiation of use of the checklist to final diagnosis was recorded. Additional diagnoses considered that were not included in the initial checklist were added to the checklist during the course of the study.ResultsThe checklist was useful in improving diagnostic efficiency (prompting consideration of diagnoses not otherwise considered upon initiation of the visit that resulted in a final plan of care) in these complex cases of recalcitrant dermatitis. Open utilization of the checklist by the investigator during the clinical encounter was well accepted by patients and families.ConclusionChecklists can be useful for complex cognitive diagnostic work.IRB approval statusUniversity Hospitals Cleveland Medical Center Institutional Review Board # 11-15-34.

Allergy Alert Test for p-Phenylenediamine-Allergic Hair Dye Users.

Contact dermatitis to hair dyes remains a health concern. Regulations in many countries require consumer self-testing for hair dyes, but no standardized procedure exists. The aim of this study was to develop a self-test protocol for an allergy alert test (AAT) that can elicit a self-noticeable alert signal in p-phenylenediamine (PPD)-allergic consumers. Simulating consumer use conditions (open application for 45 minutes after mixing with a developer), PPD-positive hair dye-allergic subjects and PPD-negative control subjects were tested on the forearm and behind the ear with experimental products containing 0.05%, 0.25%, 0.75%, and 2% PPD. Reactions were self-evaluated by subjects and independently assessed by dermatologists. The AAT caused a reaction self-noticeable on the forearm in 90.5% (38/42) and behind the ear in 93% (39/42) of the PPD-positive subjects. This was objectified by a dermatological evaluation. The strength of the AAT response and the number of responding subjects increased with increasing PPD concentrations. Allergy alert test responses were also dependent on the reaction strength of the diagnostic patch test to PPD before the study; in subjects with (+++) patch test reactions, 19 of 19 were positive. All 48 control subjects were negative to the AAT. Therefore, the AAT protocol provides a signal indicative of an allergic reaction in PPD-allergic hair dye consumers.

Cross-elicitation responses to 2-methoxymethyl-p-phenylenediamine in p-phenylenediamine-allergic individuals: Results from open use testing and diagnostic patch testing.

BackgroundAllergic contact dermatitis caused by p‐phenylenediamine (PPD) is a health concern for hair dye users. Because of its lower sensitization potency, the PPD derivative 2‐methoxymethyl‐p‐phenylenediamine (ME‐PPD) has been developed as an alternative hair dye for primary prevention. However, cross‐elicitation responses can occur in PPD‐allergic subjects.ObjectivesTo compare cross‐elicitation responses to ME‐PPD in open use and diagnostic patch testing of PPD‐allergic subjects with hair dye‐related allergic contact dermatitis.MethodsReactions to ME‐PPD were investigated in 25 PPD‐allergic subjects by performing (1) 45‐minute open use testing with a hair dye containing 2.0% of either ME‐PPD or PPD, and (2) patch testing with increasing ME‐PPD concentrations (0.1%–2.0% pet.).ResultsOf the 25 PPD‐allergic subjects, 21 (84%) reacted to open use testing with a hair dye containing 2.0% PPD, and testing with 2.0% ME‐PPD led to cross‐elicitation in 12 (48%). When patch tested with increasing ME‐PPD concentrations, 13 (52%) cross‐reacted at 0.1% (lowest dose) and 21 (84%) at 2.0% (highest dose), indicating decreased reactivity as compared with published PPD dose‐response data.ConclusionIn line with the decreased cross‐reactivity of ME‐PPD in hair dye open use testing, PPD‐allergic subjects show an attenuated cross‐elicitation dose response to ME‐PPD in patch testing.

Patch Testing in the Diagnosis of Medication Allergy

In evaluation of medication allergy, the utility of drug patch testing is dependent on both the type of drug reaction and the suspected causal drug. Epicutaneous patch tests reproduce T cell-mediated delayed hypersensitivity; thus, eruptions at least partially mediated by T cells can be confirmed by positive drug patch test (DPT) responses in some patients. These include acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), fixed drug eruptions (FDE), macular drug reactions (“morbilliform” or “exanthematous” reactions), and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Currently, literature supports that specific drugs, including antiepileptics and certain antibiotics, are most likely to produce diagnostic patch test results. However, drug patch testing cannot be used reliably for all medications. We suggest that standardized international guidelines should be developed and implemented to improve the comparability of results from drug patch testing reported in literature. Furthermore, an organized, systematic research strategy should be executed in order to gain further understanding of how and when drug patch testing can be used most effectively.

Diagnostic patch testing following tuberculosis-associated cutaneous adverse drug reactions induces systemic reactions in HIV-infected persons.

The incidence of cutaneous adverse drug reactions (CADRs) to first-line antituberculosis drugs (FLTDs) is higher in HIV-tuberculosis coinfection. However, the utility of patch testing to identify the offending drug in this patient subgroup has been poorly studied. To identify drugs causing adverse drug reactions in patients with HIV-tuberculosis coinfection. Fourteen consecutive patients underwent diagnostic work-up (patch testing followed by a skin prick test and an oral rechallenge) to pinpoint the offending drug after developing FLTD-associated CADR, which included drug rash with eosinophilia and systemic symptoms (n = 12), Stevens-Johnson syndrome (SJS, n = 1) and toxic epidermal necrolysis/SJS overlap (n = 1). A positive reaction to any of the three diagnostic modalities eliminated that drug from the regimen. Once patients were clinically stable postreaction, sequential and additive rechallenge with FLTDs was initiated. Eleven of the 14 participants with FLTD-associated CADR were HIV infected (median CD4 count 149 cells mm(-3) ). In this subgroup, patch testing resulted in generalized systemic reactions in 10 of 11 patients (91%). These included rash in 10 of 13 reactions (77%), eosinophilia in eight (62%), transaminitis in seven (54%) and fever in five (38%). Isoniazid caused six of 13 (46%) generalized systemic reactions, rifampicin four (31%), ethambutol two (15%) and pyrazinamide one reaction. Using the Common Terminology Criteria for Adverse Events, five of 13 reactions were mild, six were moderate and two were severe. There were no life-threatening or fatal reactions. In HIV-infected persons with tuberculosis-associated CADR, although patch-testing reactions to FLTD are common and tend to be associated with systemic features, they are not life threatening or fatal. These data inform clinical practice in HIV-endemic settings.

European Society of Contact Dermatitis guideline for diagnostic patch testing - recommendations on best practice.

The present guideline summarizes all aspects of patch testing for the diagnosis of contact allergy in patients suspected of suffering, or having been suffering, from allergic contact dermatitis or other delayed-type hypersensitivity skin and mucosal conditions. Sections with brief descriptions and discussions of different pertinent topics are followed by a highlighted short practical recommendation. Topics comprise, after an introduction with important definitions, materials, technique, modifications of epicutaneous testing, individual factors influencing the patch test outcome or necessitating special considerations, children, patients with occupational contact dermatitis and drug eruptions as special groups, patch testing of materials brought in by the patient, adverse effects of patch testing, and the final evaluation and patient counselling based on this judgement. Finally, short reference is made to aspects of (continuing) medical education and to electronic collection of data for epidemiological surveillance.

Cross-elicitation responses to 2-methoxymethyl-p-phenylenediamine under hair dye use conditions in p-phenylenediamine-allergic individuals.

The factors influencing elicitation responses in individuals allergic to p-phenylenediamine (PPD) in hair dyes are not well understood. Investigation of the elicitation response to the new, less-sensitizing PPD alternative 2-methoxymethyl-p-phenylenediamine (ME-PPD) under simulated hair dye use conditions. The cross-elicitation response to ME-PPD (2% in a hair dye test product for 30 min on forearm then rinsing) was analysed at days 2 and 3 in 30 PPD-allergic individuals with diagnostic patch test grades +, ++ or +++ according to the classification of the International Contact Dermatitis Research Group. Cross-reactivity to the ME-PPD-containing hair dye test product was elicited in nine of 30 subjects (30%), while 70% were negative. Cross-reactivity was elicited in two of four cases with grade +++, three of 10 with grade ++ and four of 16 with grade +. Under identical conditions, PPD was previously found to elicit a response in 21 of 27 PPD-allergic individuals. In 18 of these 21 individuals, either the strength of the cross-elicitation response to ME-PPD was decreased or no response occurred. Under simulated hair dye use conditions, a significantly lower degree of cross-elicitation to ME-PPD (30%) was observed than previously reported for PPD (32 of 38, 84%). Additionally, a decreased cross-elicitation strength was observed across all three patch test grades, likely reflecting the reduced skin-sensitization properties of ME-PPD. Consequently, careful dermatological evaluation is required to assess cross-reactivity to ME-PPD in patients allergic to hair dyes.

Contact Dermatitis: Therapeutics When Avoidance Fails

Contact dermatitis is one of the leading reasons to visit a dermatologist. There are two main types of contact dermatitis which result from exposure to chemicals: irritant contact dermatitis, which accounts for 80% of the cases, and allergic contact dermatitis, which accounts for 15%. Dermatologists must be cognizant of these diagnoses and consider appropriate and judicious use of the diagnostic patch test procedure. Once a clinically relevant allergen is diagnosed by patch testing, avoidance is the mainstay of therapy; however, medical management interventions may need to be employed in recalcitrant cases.

Applying the skin sensitisation adverse outcome pathway (AOP) to quantitative risk assessment

As documented in the recent OECD report ‘the adverse outcome pathway for skin sensitisation initiated by covalent binding to proteins’ (OECD, 2012), the chemical and biological events driving the induction of human skin sensitisation have been investigated for many years and are now well understood. Several non-animal test methods have been developed to predict sensitiser potential by measuring the impact of chemical sensitisers on these key events (Adler et al., 2011; Maxwell et al., 2011); however our ability to use these non-animal datasets for risk assessment decision-making (i.e. to establish a safe level of human exposure for a sensitising chemical) remains limited and a more mechanistic approach to data integration is required to address this challenge.Informed by our previous efforts to model the induction of skin sensitisation (Maxwell and MacKay, 2008) we are now developing two mathematical models (‘total haptenated protein’ model and ‘CD8+ T cell response’ model) that will be linked to provide predictions of the human CD8+ T cell response for a defined skin exposure to a sensitising chemical. Mathematical model development is underpinned by focussed clinical or human-relevant research activities designed to inform/challenge model predictions whilst also increasing our fundamental understanding of human skin sensitisation. With this approach, we aim to quantify the relationship between the dose of sensitiser applied to the skin and the extent of the hapten-specific T cell response that would result. Furthermore, by benchmarking our mathematical model predictions against clinical datasets (e.g. human diagnostic patch test data), instead of animal test data, we propose that this approach could represent a new paradigm for mechanistic toxicology.

Contact dermatitis – Pathomechanism and understanding of disease in clinical setting

According to the pathophysiological mechanisms involved, two major types of contact dermatitis recognized irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD). The diagnosis of either ICD or ACD is mainly depending on comprehensive clinical data (history and physical examination) as well as by performing appropriate diagnostic patch testing. Two forms of contact dermatitis may differ in early phase of development but development of clinical dermatitis have similar mechanism confusing the clinician and differentiating between ICD and ACD is often difficult in the clinical setting. This review will allow practicing physician to adopt rational clinical approach and the implementation of scientific information for therapeutic as well as preventive strategies. Journal of College of Medical Sciences-Nepal,2011,Vol-7,No-4, 70-77 DOI: http://dx.doi.org/10.3126/jcmsn.v7i4.6816