LITHUANIAN UNIVERSITY OF HEALTH SCIENCES

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LITHUANIAN UNIVERSITY OF HEALTH SCIENCES

Contact sensitization profile in patients of Kaunas clinical hospital

with suspected contact dermatitis: the results of patch testing

By

Rezwan Hussain

A thesis submitted in part fulfillment for the

degree of Master of Medicine

in the

Faculty of Medicine

Department of internal medicine

Kaunas

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SUMMARY

Author name: Rezwan Hussain

Title: Contact sensitization profile in patients of Kaunas clinical hospital with suspected contact dermatitis; the results of patch testing

Aim: The aim of the study was to determine Contact sensitization profile in patients with suspected contact dermatitis in the outpatient clinic of skin diseases of Kaunas clinical hospital using the standard European baseline patch testing technique.

Objectives:

• To evaluate the most prevalent contact allergens in the outpatient clinic of skin diseases of Kaunas clinical hospital.

• To evaluate the most prevalent contact allergens in women and men.

• To determine the rate of monosensitization and polysensitization in hypersensitive individuals.

• To evaluate the positivity of patch test results according to gender and age.

269 patients were selected from Kaunas Clinical Hospital, where they were patch tested and treated for allergic contact dermatitis. All subjects were patch-tested using Finn chambers and 24 standard chemical allergens from the European standard series. Patch tests ought to be connected to the upper back, as a result of the broad territory, encouraging the arrangement of different substances. Hairy zones ought to be maintained a strategic distance from because of low adhesion. Nonetheless, if fundamental, hair might be expelled utilizing extremely sharp edges toward hair development.

After utilization of the chambers, a sticky tape can be utilized to counteract separation and loss of bond of the tests, which encourage false negative outcomes. This progression is imperative in tropical and subtropical regions because of expanded sweating. The withdrawal of the tests is completed 48 hours after application, in a sufficiently bright place and utilizing particular plaques for the sort of chamber utilized, with openings relating to the area of allergens. The back ought to be set apart with a permanent pen, permitting future readings. The patient should return for reading 72-96 hours after use of the tests. This reading is central because a refinement response may happen over 72 hours after contact. For the analysis of the results, qualitative and quantitative, I will use Spss software to analyze the qualitative data to acquire

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the Pearson Chi-Square for evaluation of the statistical significance and also will use Microsoft Excel for analysis of quantitative data.

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Acknowledgments

I dedicate this thesis to my beloved parents, brothers and sister for their persistent support and unwavering faith in me. I would like to say a special thanks to my mother and father for their enormous love and backing to help me follow my dreams. This journey would not have been possible without the support of my family, friends, colleagues, professor and university staff. I would like to extend my thanks to my supervisor Palmira Leisyte and statistics teacher Jurate Tomkeviciute for their help, support and guidance throughout this research project.

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Conflict of interest

The author has no conflict of interest.

Abbreviation list

• ACD: Allergic contact dermatitis • AD: Atopic dermatitis

• APT: Atopic patch test

• LTT: Lymphocyte transformation test • MCI: Methylchloroisothiazolinone • MI: Methylisothiazolinone

• ICD: Irritant contact dermatitis • IL: Interleukin

• Tumor necrosis factor: TNF • OxS: Oxidative pressure • Ros: Reactive oxygen species • SCD: Systemic contact dermatitis

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Introduction

Allergic contact dermatitis (ACD) is an induced hypersensitivity to a specific allergen/allergens, which occurs when a person's skin surface comes in contact with antigen, resulting in an allergic reaction. The inflammatory response takes place in the skin after percutaneous absorption of antigen resulting in recruitment of previously sensitized, antigen-specific T lymphocytes into the surface (1, 2). It starts as a standard cell-mediated response to an intracellular pathogen such as bacteria, fungi, and virus. However, the persistence of allergen sensitizes TDTH cells, causing secretion of inflammatory cytokines. The cytokines then activate the phagocytic cells resulting in non-specific tissue destruction and induce inflammation where symptoms usually take 24 – 72 hours to develop. The site of the inflammatory reaction, which came in contact with an allergen in a sensitized individual result in redness, papules, and vesicles, followed by scaling and dry skin, these symptoms in Lithuania are most commonly caused by Nickel, cobalt chloride, Potassium dichromate, Formaldehyde and MCI/MI (6) There are two types of Contact dermatitis, Allergic contact dermatitis and Irritant contact dermatitis (ICD), readily distinguishable based on the characteristics of symptoms and mechanism of response. ICD is a non-immune related physical and chemical modification of the skin due to pro-inflammatory and lethal effects of organic solvents, soaps, environmental factors, and acids. ACD corresponds to type IV immune response, with an induction phase (afferent pathway) and an elicitation phase (efferent pathway), involving a complex series of events. The induction phase includes the Langerhans cells to uptake, processing, and

presentation of the antigen by local antigen-presenting cells, and migrate to the limb node where they activate the T cells and activate production of memory T cells and in the elicitation phase, TH1 cells that have been primed by the previous exposure to the antigen which migrate

and become activated because these cells are rare, so there is little inflammation to attract the specific memory T cells to the site of dermis. ACD is very common in communities, however, hard to determine the actual rate of incidence as patients are often self-diagnosed, self-treat and are brought to a medical practitioners attention at various points, such as the emergency room, general practice, and urgent care clinics (4).

Patch testing is a gold standard technique discovered by Jozef Jadassohn in 1985 that revolutionized the way of identifying the specific allergens triggering ACD. Different countries and centers usually have their own patch test traditions despite the efforts to standardize the procedure by international societies (5).

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When performing patch testing, it must be recalled that the patch test is a biological incitement test and in that capacity, the result is subject to different variables including the test framework and test material, the organic/functional status of the tested individual, and the dependable dermatologist. To get desired bioavailability of a hapten, one can impact the accompanying five factors.

• Intrinsic penetration capacity • Concentration, dose

• Vehicle

• Exclusivity of patch test system and tape • Exposure time

Patch testing is a sophisticated but very useful mean to establish contact allergy although the diagnosis of allergic contact dermatitis comes from the combination of patch-test results and clinical data. However, different countries and centers usually have their own patch test traditions despite the efforts to standardize the procedure by international societies. Thus, makes it difficult to compare results obtained in different countries (3).

The European standard series is often used across Lithuania, which is the baseline series of most frequently appearing allergens and the choice of test concentration is based on reading and interpretation of complex test results that requires training and experience with a clinical history of contact dermatitis (4).

The diagnosis of ACD is based on clinical history and patch testing. The patch test determines whether a specific substance causes allergic inflammation of a patient’s skin. The positive patch test indicates contact sensitization of present or past relevance. However, sometimes the test gives false-positive and false-negative results, which can be correctly interpreted only by experienced allergists (6).

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AIM AND OBJECTIVES OF THESIS

The aim of the study was to determine contact sensitization profile in patients with suspected contact dermatitis in the outpatient clinic of skin diseases of Kaunas Clinical Hospital using the standard European baseline patch testing technique.

Objectives

• To evaluate the most prevalent contact allergens in the outpatient clinic of skin diseases of Kaunas clinical hospital.

• To evaluate the most prevalent contact allergens in women and men.

• To determine the rate of monosensitization and polysensitization in hypersensitive individuals.

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Literature review

In Lithuania as in the most Eastern European countries, atopic dermatitis is considered to be mainly an allergic disease (both by patients and clinicians). Thus, almost all patients

diagnosed with atopic dermatitis are referred firstly to allergologists and later to

dermatologists. In Scandinavia and most Western European countries atopic dermatitis is diagnosed and treated mostly by dermatologists (3).

The frequencies of sensitization to allergens of the European baseline series, often supplemented by region-specific contact allergens, are continuously analyzed in most European countries. On the basis of resulting findings, the composition of the European baseline series is revised continually (last modified in 2008) and the relevance to allergen exposure is maintained (7). Monitoring time trends of contact allergy allow evaluation of the need for, and effectiveness of, preventive measures (8).

Pathophysiology of ACD

ACD is a type IV, a delayed-type reaction that is caused by skin contact with allergens that activate antigen-specific T cells in a sensitized individual. The sensitized T cells are primarily T-helper 1 (TH1) type. In the sensitization phase, innate immunity is activated through

keratinocyte release of interleukin (IL)-1a, IL-1b, tumor necrosis factor alpha, granulocyte-macrophage-colony-stimulating factor, and ILs-8 and -18. Langerhans and dermal dendritic cells uptake the allergen and migrate to the regional lymph nodes to activate antigen-specific T cells. These T cells then proliferate and enter the circulation and site of exposure. When exposed to the allergen again, antigen-specific T cells are activated through the release of cytokines and induce an inflammatory process. We now also recognize that patients with atopic dermatitis (AD) have barrier dysfunction that contributes to ACD in that population. Dermal dendritic cells, as opposed to epidermal Langerhans cells, play an essential role in educating naive T cells in the lymph node to become antigen-specific effector cells during cutaneous sensitization.The recognition of skin resident T cells has enlightened our understanding of the role of Langerhans cells. Langerhans cells have now been shown to interact with skin resident T cells and generally promote tolerance when encountering antigens by stimulating Treg cells (9).

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Top 5 most frequent allergens in Lithuania

Consecutive patients with suspected ACD were tested in Lithuania in the years 2010–2012. A Positive patch test reaction to at least one allergen was observed. The top 5 most frequent allergens in Lithuania were as follows: nickel sulphate,

methylchloroisothiazolinone/methylisothiazolinone (MCI/MI), cobalt chloride, potassium dichromate, and formaldehyde (3). Nickel is the leading allergen in Lithuania, with the sex and age factors strongly influencing the prevalence of nickel sensitization. Refer to sex-related and age-related patterns of nickel exposure, early ear piercing, and contact with

nickel-releasing jewelry (8). Women under 40 years are more sensitive to nickel than older ones (10). Factors with correlation to delayed hypersensitivity

Influence of age

Allergic contact dermatitis (ACD) in children appears to be on the increase, and contact sensitization may already begin in infancy (11). It has been reported children with atopic dermatitis have tested positive to more than one allergen and statistically more girls than boys (1). Younger patients were patch test-positive to nickel sulfate almost two times more often than older ones (8). Allergic contact dermatitis (ACD) in children appears to be on the increase (9).

Gender-related patterns

One of the main allergens in the group is nickel, age, and sex strongly influencing the

prevalence of sensitization. These results refer to sex-related and age-related patterns of nickel exposure, early ear piercing, and contact with nickel-releasing jewelry (8). While the

proportion of positive patch tests is significantly lower among men than women (10). Women were significantly more often patch test-positive to nickel sulfate than men (8). The

correlation between positive patch test in men being lower than women could be related to fashion related jewelry. The more than two-crease higher prevalence in women is because of various exposures, for example, nickel through the piercing. Nonetheless, regardless of whether nickel isn't considered, women still have a higher pervasiveness for ACD. Hormonal impacts likely cause this higher powerlessness. (12) Ladies have higher immunoglobulin levels (IgM and IgG) than men, and more grounded cell-intervened immune reactions. Both in animal studies and in people, there is a prevalence of immune system illness in ladies

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contrasted with men. The fundamental explanation behind female dominance in clinical patch test contemplates in the high number of nickel and cobalt-delicate ladies. This is undoubtedly an outcome of various introductions, with ear puncturing the primary hazard factor for nickel hypersensitivity in ladies. A current investigation of nickel hypersensitivity in men with pierced ears affirmed the part of ear puncturing as a hazard factor for nickel sharpening additionally in men, yet the recurrence of nickel sensitivity in men with pierced ears was lower than the repetition announced in ladies. The impact of sex hormones on enlistment and elicitation of contact sensitivity is to a great extent obscure. In a pilot study, think about the reaction to DNCB was improved in ladies getting oral prophylactic hormones and a

preliminary report shows that the cutaneous reactivity to fix testing varies inside the menstrual cycle. The restricted information in this field is uncertain, and merits encourage efficient assessment. (13)

Atopic

Atopic down-regulate Th1 cells, which discloses their inclination to serious viral contaminations, especially with herpes simplex. Given this Th1-cell down-regulation, a diminished affinity to contact dermatitis is normal. Clinical investigations tending to this issue are conflicting, yet most locate a reduced propensity to contact sharpening. A few studies propose that particularly patients with extreme atopic dermatitis have a diminished capacity to create contact sensitivities. (13)

Stress

There has been an investigation found to help aggravation and oxidative pressure, coming about because of overproduction of receptive oxygen and also responsive nitrogen species nearby with the associative inadequacy of against oxidative resistances of an individual, is indivisibly identified with physiological and infection states. Introductory allergen refinement and in addition advancement of pathogenic insusceptible reaction has been determined with an ascent in foundational interleukin – IL-6, IL-1, and furthermore tumor corruption factor (TNF-irritation and oxidative pressure (OxS)), the last characterized as an overproduction of

receptive oxygen and in addition nitrogen species (ROS and RSN, resp.) with corresponding inadequacy of antioxidative resistances of the body, have been observed to be inseparably associated in physiological and also ailment states. In hypersensitive contact dermatitis, hoisted fundamental levels of IL-6, IL-1, and tumor necrosis factor (TNF) and ROS are

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proposed to take an interest in the underlying allergen sharpening and also in the advancement of pathogenic unfavorably susceptible reactions.

Dietary

While both ACD and systemic contact dermatitis (SCD) are interceded by White blood cells, the pathogenesis of SCD isn't surely understood. A crucial inquiry is a reason just a subset of patients with ACD will respond to allergens upon dietary presentation. No research center test is accessible to decide whether SCD likewise influences a patient with ACD. In this manner, if a patient with ACD to nickel or another all around perceived dietary allergen does not enhance shirking of cutaneous contact, dietary evasion would be prescribed for a time of 6 weeks to two months. It is additionally essential to take note of that SCD may happen in conjunction with Promotion. In these cases, dermatitis may enhance with allergen evasion, however not resolve, because of the underlying AD. (14)

Implants

Complex immune responses that occur around the implants may bring about torment, irritation, and relaxing of the implant. Nickel, cobalt, and chromium are considered as the most common metals inspiring both cutaneous and extracutaneous unfavorably susceptible responses from an unending inner presentation. Sporadically, other metal particles and bone bond segments cause excessive touchiness responses.

Concomitant diseases (atopic dermatitis)

In spite of the way that audits have shown conflicting results, the standard appreciation is that contact sharpening is less ceaseless in patients with atopic dermatitis, inferable from a

prevented cell safe response of the skin provoking a lessened ability to fight skin defilements and raise Type IV sensitivities.

Latest studies, be that as it may, have demonstrated that contact sharpening may vary with the seriousness of atopic dermatitis, proposing an additionally complicated relationship. An exploratory examination found that solitary 33% of patients with outrageous atopic dermatitis could be honed with the powerful sensitizer dinitrochlorobenzene, as differentiated and 95% and 100% of patients with direct and gentle atopic skin inflammation, separately. Similarly, an observational examination found a decreased transcendence of contact refinement in patients

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with outrageous atopic dermatitis, yet not in patients with gentle to direct disease. Conflicting results have in like manner been appropriated, uncovering a higher repeat of positive fix test response in patients with extraordinary atopic dermatitis than in those with direct infection and mellow ailment. (15)

Quality of life

Skin conditions can diminish personal satisfaction, characterized by the World Wellbeing Association as a condition of finish physical, mental, and social prosperity. It can regularly be ascribed to feeling constrained to look ordinary or conform to social models. (16)

Psychological

Skin hypersensitive conditions, including urticaria, unfavorably susceptible contact dermatitis and atopic dermatitis, might be related with a very diminished personal satisfaction,

particularly considering proficient or school exercises. Writing information recommends that patients experiencing unfavorably susceptible contact dermatitis and urticaria have a higher predominance of a mental issue than the general population (for the most part anxiety disorder – fears, trailed by depressive and somatoform issue).

The psychosocial outcomes of having a skin condition can bring about depression.

Manifestations include: Feeling down, low, pitiful, or weepy, loss of delight or inspiration, sleep unsettling influence, weakness, Appetite changes, trouble with memory as well as fixation, excessive sentiments of blame, a general absence of action and social engagement and suicidal thoughts. (16)

Drugs

It is a general clinical affair that systemic prednisolone in a dosage surpassing 15 mg/day may reduce or smother unfavorably susceptible patch test responses, as may topical corticoid treatment. Antihistamines and disodiumcromoglycate don't appear to impact the unfavorably susceptible contact dermatitis response fundamentally. The impact of azathioprine and non-steroidal calming drugs on the result of fix test responses is unexplored.

Introduction to bright light, particularly UVB [78, 79] and PUVA [80, 81], may lessen the danger of refinement and briefly reduce the capacity to inspire unfavorably susceptible

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responses in sharpened people. (9)

Clinical differences between irritant contact dermatitis and allergic contact dermatitis The following table outlines some essential contrasts between the two sorts:

Irritant contact dermatitis Allergic contact dermatitis

Often acute in onset Acute, subacute, or chronic in onset

Appears after first exposure Sensitization necessary before the reaction occurs

Decrescendo phenomenon - reaches a rapid peak and starts to resolve

Crescendo phenomenon - keeps worsening and resolves more slowly

Red swollen skin, sometimes ulcerated, in acute form

Vesicles are typical, but ulceration or skin necrosis is rare in acute cases

Thickening, erosion, fissuring, or shiny skin

following chronic irritation Vesicles may not be found in chronic cases

Sharply delimited rash in the area of contact More ill-defined boundaries but lesions usually found in areas of contact

Burning or stinging of the area, which is intensely

tender Intensely pruritic lesions

Allergens from the European baseline series with high sensitization in Lithuania

The most prevalent allergens in atopic dermatitis and healthy groups were: nickel sulfate, chemicals, fragrances, preservatives and plants (1). The Nickel Directive in Lithuania is adopted since 2003, while a kind of restriction in nickel exposure has been present in Sweden already since 1991 when nickel-containing piercers or rings were banned if the alloy contained more than 0.05% nickel (3). Nickel was found to be the leading allergen in Lithuania, with the sex and age factors strongly influencing the prevalence of nickel sensitization (10). Preventive measures should be taken to avoid contact with potential allergens (1).

Nickel

Nickel is a silvery-white lustrous, hard and ductile transition metal that is widely used in alloys to improve resistance to corrosion, wear, and abrasion. Nickel comes in various forms and is the most common allergen particular in women through the use of jewelry. There are a

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vast amount of applications of nickel in everyday life such as in batteries, coins or keys, jewelry, orthopedic plates, metal plating, and wristwatch. However, there is a

Dimethylglyoxime test for detecting nickel objects. Metallic nickel (only after corrosion), nickel salts gives rise to CD and sensitization is not usually occupational but through few of the components listed above (4).

Cobalt chloride

A grayish, hard, attractive, bendable and to some degree moldable metal, which utilized in the production of cobalt alloy and salts. The Cobalt salts are typically hued so primarily used as shades for glass, ceramics, cosmetics and hair dyes. There are occupational related (bond, paints, gums, paint driers), metals (adornments, coins), medications (metal dental prostheses and joints, vitamin B12) causing sharpening. Be that as it may, the most successive reason for sharpening to this metal is nickel-plated objects, which quite often contain cobalt (4).

Fragrance mix

Commercial perfumes are complex mixtures of natural essential oils and synthetic

compounds. They are part of the composition of many products including cosmetics (the most frequent cause of allergic contact dermatitis due to cosmetics), topical medication, detergents, air fresheners, and food. Fragrance mix I was developed in the late 1970s, and consist of eight ingredients, each at a concentration of 1%: Amyl cinnamal, Cinnamal, Cinnamyl alcohol, Eugenol, Evernia prunastri, Geraniol, Hydroxycitronellal, Isoeugenol. The uses of fragrance mix involve cosmetics, perfumes, clothing, food, household products, medication and

dentistry (4). Fragrance substances are second only to metals as a cause of contact allergy; between 1.1% and 8% of the general population have a contact allergy to fragrance substances (17,18)

MCI/MI

Isothiazolinones is a cosmetic preservative. Isothiazolinones are utilized broadly as powerful biocides to safeguard the water substance of beauty care products, toiletries, family unit, and modern items, for example, cosmetics: shampoos, cleansers, conditioners, gels (hair and body), creams and moisturizers for the skin, confront packs, and so forth; Family items: cleansers, bubble showers, cement, pastes, wet wipes, cleansing agents, cleaning items, bathroom tissue. Stream motor fuel, latex emulsions, trimming oils, aerating and cooling,

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drain tests, lubricants and coolants, paints, pesticides, colors, varnishes, additives, printing inks, X-beams, and so on; and Others: biocides for swimming pool water (4).

Corticosteroids

Contact sensitivity to corticosteroids has been progressively perceived worldwide as an issue of extensive clinical and helpful significance. The rate of corticosteroid sensitivity saw (from 0.5% to 5%) differs in each report starting with one focus then onto the next (1±6) and relies upon a few factors, for example, mindfulness and testing for corticosteroid hypersensitivity, tolerant choice, going before skin infection, endorsing propensities and kind of corticosteroids utilized as a part of every nation, and the test and perusing strategies utilized. Most instances of contact sensitivities would be missed if corticosteroids were not routinely tried and

hypersensitive responses can be seen to corticosteroids directed by inward breath arrangements in the treatment of rhinitis or bronchial asthma.

Regions of the body affected by ACD

Allergic contact dermatitis arises some hours after contact with the responsible material. It settles down over some days providing the skin is no longer in contact with the allergen. Allergic contact dermatitis is generally confined to the site of contact with the allergen, but it may extend outside the contact area or become generalized.

• Transmission from the fingers can lead to dermatitis on the eyelids and genitals. • Dermatitis is unlikely to be due to a specific allergen if the area of skin most in contact

with that allergen is unaffected.

• The affected skin may be red and itchy, swollen and blistered, or dry and bumpy. Patch testing

Patch testing attempts to recreate an allergic reaction to nonirritating concentrations of an allergen that is suspended in a vehicle. The decisions to perform patch testing, and which allergen to test depends on many factors. Some common indications for patch testing include (1) distributions that are highly suggestive of ACD—for example, ACD of the hands, feet, face, and eyelid, as well as unilateral presentations (9). Detailed knowledge of the clinical features of the skin's reactions to various external substances is essential in making the correct diagnosis of contact dermatitis (11). Reading and grading the results of patch testing is

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somewhat subjective and dependent on descriptive morphology. This creates a significant degree of variation in how patch tests are interpreted by different clinicians (9). Physicians usually grade patch test reading of allergens based on the characteristics that vary between 1+ and 3+ highlighting the severity of the reaction. (Table 1)

Table 1. Classification of patch test readings according to the International Contact Dermatitis Research Group

Reaction Definition

?+ Doubtful reaction; faint erythema only

1+ Weakly positive reaction; erythema, infiltration, and possible papules

2+ Strongly positive reaction; erythema, infiltration, papules, and vesicles

3+ Extreme positive reaction; intense erythema, infiltration, and coalescing vesicles

_ Negative reaction

IR Irritant reaction: patterns include follicular, glazed erythema, and ulceration

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Patch result illustration

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Positive and negative patch testing; False-negative reactions can be caused by: 1- Failure to perform a delayed reading

2- Testing to an inappropriately low concentration of allergen 3- Poor patch test placement or loosening of patch tests 4- Concurrent immunosuppression.

False-positive reactions can be caused by: 1- Testing with borderline

2- Testing beyond the irritancy threshold 3- Excited skin syndrome

4- Patients with a background of dermatitis (4). Indications

Patch tests are indicated:

1- For patients with a diagnostic hypothesis of CD

2- Patients with other skin conditions that may be aggravated by CD (atopic dermatitis, seborrheic dermatitis and stasis, nummular eczema, psoriasis, and dyshidrosis) 3- Patients which chronic eczema without an established etiology

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RESEARCH METHODOLOGY AND METHODS

269 patients were selected from Kaunas Clinical Hospital, where they were patch tested and treated for allergic contact dermatitis. All subjects were patch-tested using Finn chambers and 24 standard chemical allergens from the European standard series. Patch tests ought to be connected to the upper back, as a result of the broad territory, encouraging the arrangement of different substances. Hairy zones ought to be maintained a strategic distance from because of low adhesion. Nonetheless, if fundamental, hair might be expelled utilizing extremely sharp edges toward hair development.

After utilization of the chambers, a sticky tape can be utilized to counteract separation and loss of bond of the tests, which encourage false negative outcomes. This progression is imperative in tropical and subtropical regions because of expanded sweating. The withdrawal of the tests is completed 48 hours after application, in a sufficiently bright place and utilizing particular plaques for the sort of chamber utilized, with openings relating to the area of allergens. The back ought to be set apart with a permanent pen, permitting future readings. The patient should return for reading 72-96 hours after use of the tests. This reading is central in light of the fact that a refinement response may happen over 72 hours after contact.

For the analysis of the results, qualitative and quantitative, I will use Spss software to analyse the qualitative data to acquire the Pearson Chi-Square for evaluation of the statistical

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Results

5.1 Main characteristics of the patients who participated in the study

A total of 269 patients were selected from a list of patients who were patch tested in 2015, 2016 and 2017 in Kaunas Clinical Hospital, 30, 92 and 147 patients respectably. 217 (80%) of them were female and the 52 (17%) male. The female: male ratio of the patient is involved in the study population is presented in table 1.

To evaluate the Gender ratio of the patients involved in the study

Table 1. Female: male ratio of the patients involved in the study according to the year of examination

Gender

Total

Male Female

Year 2015 Count 7a 23a 30

% within Gender 13.5% 10.6% 11.2% 2016 Count 11a 81b 92 % within Gender 21.2% 37.3% 34.2%

2017 Count 34a 113a 147

% within Gender 65.4% 52.1% 54.6% Total Count 52 217 269 % within Gender 100.0% 100.0% 100.0%

The female population dominated this study, as the proportion of women was quadruple of men. The mean age average of the whole study population was 40.28 (SD 16.45) years. The mean average age of the female was 41.7 (SD 16.32) years while in the male it was 39.7 (SD 17.05) years in the overall study. The youngest patient in the study population was 13, and the oldest was 90 years old.

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Table 2. Distribution of patients according to gender and age group

Age group Female Male Total

N = 217 N= 52 N=269 10 ≤ x ≤ 29 63 16 79 29.03% 30.77% 29.37% 30 ≤ x ≤ 49 80 22 101 36.87% 42.31% 37.55% 50 ≤ x ≤ 69 60 11 71 27.65% 21.15% 26.39% 70 ≤ x ≤ 89 14 3 17 6.45% 5.77% 6.32%

From the study population who tested positive for the patch test, age group 30 ≤ x ≤ 49 was found to be the most prominent group with the highest number of individuals who tested positive to a contact allergen in both genders, (respectively 36.87% in female and 42.31% in male).

5.2 The most prevalent contact allergens in the study population.

The results of the patch test and most prevalent allergen are presented in table 3. Textile dye, nickel, and cobalt were the most prevalent contact allergens in this study population. Patch test results for textile dye were found to be positive in 41.81% of patients, for nickel – 25.69% of patients and cobalt – 21.47% followed by fragrance mix 1 (15.82%), PPD (11.30%) and Peru balsam (11.30%).

Table 3. Hypersensitivity to contact allergens of all patients according to year (2015,2016 and 2017) Allergens (n=16) 2015 (n=54) 2016 (n=107) 2017 (n=177) Total Potassium dichromate 1 1 8 10 5.65% PPD 2 4 14 20 11.30% Thuriam mix 1 3 4 8 4.52% Neomycin sulphate 2 0 2 4 2.26% Cobalt chloride 2 9 27 38 21.47% Benzocaine 0 0 5 5 2.82% Nickel sulphate 3 15 28 46 25.99% Clioquinol 0 1 3 4 2.26% Colophonium 2 3 11 16 9.04%

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IPPD 0 5 3 8 4.52% Lanolin alcohol 0 5 1 6 3.39% Mercapto mix 1 5 4 10 5.65% Epoxy resin 1 2 6 9 5.08% Peru balsam 1 5 14 20 11.30% PTBP 0 1 1 2 1.13% MBT 0 3 0 3 1.69% Formaldehyde 0 3 3 6 3.39% Fragrance mix 1 0 7 21 28 15.82%

Sesquiterpene lactone mix 0 5 6 11 6.21%

Quaternium-15 1 1 3 5 2.82% 2-methoxy-6-n-pentyl-4 -benzoquinone 0 2 2 4 2.26% Methylisothiazolinone + Methylchloroisothiazolinone 2 6 6 14 7.91% Budesonide 0 1 10 11 6.21% Tixocortol-21-pivalate 1 1 1 3 1.69% Methyldibromo glutaronitrile 1 1 4 6 3.39% Fragrance mix 2 1 3 7 11 6.21% Hydroxyisohexyl 3-cyclohexene carboxaldehyde 0 3 7 10 5.65% Methylisothiazolinone 1 10 6 17 9.60%

Textile dye mix 6 15 53 74 41.81%

5.3 The prevalence of prevalent contact allergens according to gender.

The results of the patch tests and most prevalent allergens are presented in table 4.

Sensitization to textile dye is found to be most prevalent contact allergen in both genders. 32.77% of female populations were prone while 9.04% of male, (p=0.558). While nickel sulphate was the second most prevalent contact allergen among females (24.3%) and followed by cobalt chloride (16.39%). Among male, the second most prevalent allergen was cobalt (5.08%) and third - PPD (3.39%).

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Table 4. Hypersensitivity to contact allergens of all patients according to gender

2015 (n=19) 2016 (n=54) 2017 (n=107) Total (n=177) Allergens Female Male Female Male Female Male Female Male

Potassium dichromate 1 1 5 3 7 (3.95%) 3 (1.69%) PPD 2 2 2 10 4 14 (17.52%) 6 (3.39%) Thuriam mix 1 3 2 2 5 (5.65%) 3 (1.69%) Neomycin sulphate 1 1 2 1 (0.57%) 3 (1.69%) Cobalt chloride 2 7 2 20 7 29 (16.39%) 9 (5.08%) Benzocaine 4 1 4 (2.25%) 1 (0.57%) Nickel sulphate 3 15 25 3 43 (24.30%) 3 (1.69%) Clioquinol 1 3 4 (2.25%) 0 Colophonium 2 3 10 1 15 (8.47%) 1 (0.57%) ParaBENmix 2 1 1 3 (1.69%) 1 (0.57%) IPPD 4 1 3 7 (3.95%) 1 (0.57%) Lanolin alcohol 4 1 1 4 (2.25%) 2 (1.13%) Mercapto mix 1 4 1 1 3 5 (5.65%) 5 (2.82%) Epoxy resin 1 2 4 2 7 (6.21%) 2 (1.13%) Peru balsam 1 5 10 4 16 (9.05%) 4 (2.25%) PTBP 1 1 2 (1.13%) 0 MBT 3 3 (1.69%) 0 Formaldehyde 3 1 2 4 (2.25%) 2 (1.13%) Fragrance mix 1 7 17 4 24 (13.57%) 4 (2.25%)

Sesquiterpene lactone mix 4 1 4 2 8 (4.52%) 3 (1.69%)

Quaternium-15 1 1 3 4 (2.25%) 1 (0.57%) 2-methoxy-6-n-pentyl-4 -benzoquinone 1 1 2 3 (1.69%) 1 (0.57%) Methylisothiazolinone + Methylchloroisothiazolinone 2 6 4 2 12 (6.78%)) 2 (1.13%) Budesonide 1 7 3 8 (4.52%) 3 (1.69%) Tixocortol-21-pivalate 1 1 1 2 (1.13%) 1 (0.57%) Methyldibromo glutaronitrile 1 1 4 6 (3.39%) 0 Fragrance mix 2 1 3 5 2 9 (5.08%) 2 (1.13%) Hydroxyisohexyl 3-cyclohexene carboxaldehyde 3 6 1 9 (5.08%) 1 (0.57%) Methylisothiazolinone 1 10 6 17 (9.60%) 0

Textile dye mix 3 3 13 2 42 11 58 (32.77%) 16 (9.04%)

Analyses of trends in hypersensitivities of separate allergen found to be most prevalent are presented in tables 5,6 and 7. Hypersensitivity to textile dye showed a rising trend in female population over the three years while fluctuated in the male population. The frequency of hypersensitivity to textile dye was found that male were more sensitive than female in 2015

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(respectively 42.9% and 13%) but not in 2016 or 2017, (p=0.084). Hypersensitivity to nickel sulphate increased over the course of 3 years in the female population. In 2017 there were 8.8% of male and 23.9% of female that was found to be hypersensitive to nickel, (p=0.056). This illustrates there were more women prone to nickel hypersensitivity in comparison to men. During the three years, it was found that women overall were more hypersensitive to nickel, (respectively 5.8% male and 20.7% female), (p=0.011). Hypersensitivity to cobalt chloride did not illustrate a significant increase but only a slight increase in the male population each year. The most prevalent contact allergens among male were textile dye (9.04%) followed by cobalt chloride (5.08%) and PPD (3.39%).

Table 5. The frequency of hypersensitivity to Textile dye according to the year of data collection and gender.

Textile Dye Year Gender Total Male Female 2015 Textile Dye Yes Count 3a 3a 6 % within Gender 42.9% 13.0% 20.0% No Count 4a 20a 24 % within Gender 57.1% 87.0% 80.0% Total Count 7 23 30 % within Gender 100.0% 100.0% 100.0% p=0.084 2016 Textile

Dye Yes Count % within 2a 13a 15

Gender 18.2% 16.0% 16.3% No Count 9a 68a 77 % within Gender 81.8% 84.0% 83.7% Total Count 11 81 92 % within Gender 100.0% 100.0% 100.0% p=0.857 2017 Textile

Dye Yes Count % within 11a 42a 53

Gender

32.4% 37.2% 36.1%

No Count 23a 71a 94

% within

Gender 67.6% 62.8% 63.9%

Total Count 34 113 147

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Gender

p= 0.608

Total Textile Dye

Yes Count 16a 58a 74

% within Gender

30.8% 26.7% 27.5%

No Count 36a 159a 195

% within Gender 69.2% 73.3% 72.5% Total Count 52 217 269 % within Gender 100.0% 100.0% 100.0% p=0.558

Table 6. The frequency of hypersensitivity to nickel sulphate according to the year of data collection and gender.

Nickel sulphate

Year

Gender

Total Male Female

2015 Nickel Yes Count 0a 3a 3

% within Gender 0.0% 13.0% 10.0% No Count 7a 20a 27 % within Gender 100.0% 87.0% 90.0% Total Count 7 23 30 % within Gender 100.0% 100.0% 100.0% p=0.314

% within Gender

0.0% 18.5% 16.3%

No Count 11a 66a 77

% within Gender

8.8% 23.9% 20.4%

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Total Count 34 113 147 % within

Gender 100.0% 100.0% 100.0%

p=0.056

Total Nickel Yes Count 3a 45b 48

% within Gender 5.8% 20.7% 17.8% No Count 49a 172b 221 % within Gender 94.2% 79.3% 82.2% Total Count 52 217 269 % within Gender 100.0% 100.0% 100.0% p=0.011

Table 7. The frequency of hypersensitivity to cobalt chloride according to the year of data collection and gender.

Cobalt sulphate Year

Gender

Total Male Female

2015 Cobalt Yes Count 1a 2a 3

% within

Gender 20.6% 19.5% 19.7%

% within Gender

79.4% 80.5% 80.3%

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% within Gender

100.0% 100.0% 100.0%

p=0.886

Total Cobalt Yes Count 10a 31a 41

% within Gender

19.2% 14.3% 15.2%

% within Gender 80.8% 85.7% 84.8% Total Count 52 217 269 % within Gender 100.0% 100.0% 100.0% p=0.373 Table 5.2.3

5.4 The frequency of monosensitization and polysensitization in hypersensitive individuals.

Table 8 illustrates the frequency of positivity of patch testing. Overall 65.8% of the study populations were with positive patch test results and with confirmed contact

hypersensitivity. Each year the proportion of positive patch test results is increasing in the study population.

Table 8. Demonstrates positivity of patch testing according to gender in different years

Gender

Patch test

2015 2016 2017 Total

Male Count % within gender

Positive Negative Positive Negative Positive Negative Positive Negative 3 1.11% 4 1.49% 5 1.86% 6 2.23% 24 8.92% 11 4.09% 32 11.89% 21 7.8%

Female Count % within gender 13 4.83% 10 3.72% 49 18.21% 31 11.52% 83 30.85% 30 11.15% 145 53.90% 71 26.39% Total

(n=269) Count % within gender 16 5.95% 14 5.20% 55 20.07% 37 13.76% 107 39.78% 41 15.24% 177 65.80% 92 34.20%

Table 9 shows the results of those with positive patch test according to the year of data collection and gender. Overall it shows 62.7% of patients were polysensitized versus 37.3% were found to be monosensitization. According to gender, a trend was revealed that 59.4% of male and 63.4% female population were polysensitized. In 2017 there was a more significant

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proportion of females with polysensitization than in previous two years (respectively 53.8%, 58.1% and 71.1% of female, p>0.05).

Table 9. The frequency of monosensitivity and polysensitivity according to the year of data collection and gender.

Hypersensitivity in the study population Year

Gender

Total

Male Female

2015 Allergens Monosensitized Count 1 6 7

% within Gender 33.3% 46.2% 43.8% Polysensitization Count 2 7 9 % within Gender 66.7% 53.8% 56.3% Total Count 3 13 16 % within Gender 100.0% 100.0% 100.0% P=0.687

% within Gender 37.5% 28.9% 30.8% Polysensitization Count 15 59 74 % within Gender 62.5% 71.1% 69.2% Total Count 24 83 107

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% within Gender

100.0% 100.0% 100.0%

P=0.423

Total Allergens Monosensitized Count 13 53 66

Table 10 shows the frequency of monosenstivity and polysensitivity in different age groups. In 2015 monosensitization was most frequent among in young group of 10 – 29 years old, (p=0.002). Based on the data of the study population there was no statistical difference among other age groups or years of data collection. Polysensitization was most frequent in the age group 30 ≤ x ≤ 49 years old (71.2% of patients were polysensitized).

Table 10. The frequency of monosensitivity and polysensitivity among different groups in the different year of data collection.

Hypersensitivity in study population among age groups Year

Age groups

Total 10-29 30-49 50-69 70-89

2015 Allergens Monosensitized Count 7 0 0 0 7

% within age group 87.5% 0.0% 0.0% 0.0% 43.8% Polysensitization Count 1 3 5 0 9 % within age group 12.5% 100.0% 100.0% 0.0% 56.3% Total Count 8 3 5 0 16 % within age group 100.0% 100.0% 100.0% 0.0% 100.0% P=0.002

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age group Polysensitization Count 6 13 8 1 28 % within age group 50.0% 61.9% 42.1% 50.0% 51.9% Total Count 12 21 19 2 54 % within age group 100.0% 100.0% 100.0% 100.0% 100.0% P=0.661

Total Allergens Monosensitized Count 23 21 18 4 66

5.5 Positivity of patch test results according to gender and age groups.

Table 11 shows patch test results in individual genders according to the year of data

collection. Data in both sexes illustrates an upward trend in the proportion of positive patch test results; respectively 56.5%, 60.5% and 73.5% in females and respectively 42.9%, 45.5% and 70.6% in males, (p>0.005).

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Table 11. Patch test results according to gender in the year of data collection

Patch test results of 2015, 2016 and 2017 Year

Gender

Total

Male Female

2015 Positive

patch test Yes Count % within 3a 13a 16

Gender 42.9% 56.5% 53.3% No Count 4a 10a 14 % within Gender 57.1% 43.5% 46.7% Total Count 7 23 30 % within Gender 100.0% 100.0% 100.0% p=0.526 2016 Positive

patch test Yes Count % within 5a 49a 54

Gender 45.5% 60.5% 58.7% No Count 6a 32a 38 % within Gender 54.5% 39.5% 41.3% Total Count 11 81 92 % within Gender 100.0% 100.0% 100.0% p=0.342 2017 Positive patch test

% within

Gender 70.6% 73.5% 72.8%

No Count 10a 30a 40

% within Gender 29.4% 26.5% 27.2% Total Count 34 113 147 % within Gender 100.0% 100.0% 100.0% p=0.742 Total Positive patch test

% within Gender

61.5% 66.8% 65.8%

No Count 20a 72a 92

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Table 12 shows patch test results classified into age groups. The highest proportion of

individuals with positive patch test was detected in the age group 30 ≤ x ≤49 years old (71.6% of patients of this age group), (respectively 72.7% in male and 71.3% in female).

Table 12. Patch test results according to age groups and gender.

Patch test results within the age group in among both Genders Gender Age group Total 10-29 30-49 50-69 70-89 Male Positive patch test

Yes Count 9a 16a 6a 0a 31

% within age group 56.3% 72.7% 54.5% 0.0% 60.8% No Count 7a 6a 5a 3a 21 % within age group 43.8% 27.3% 45.5% 100.0% 39.2% Total Count 16 22 11 2 52 % within age group 100.0% 100.0% 100.0% 100.0% 100.0% P=0.204 Female Positive

patch test Yes Count _{% within} 40a 57a 41a 8a 145 age group

63.5% 71.3% 68.3% 53.3% 66.8%

No Count 23a 23a 19a 7a 72

% within age group 36.5% 28.8% 31.27% 46.7% 33.2% Total Count 63 80 60 15 217 % within age group 100.0% 100.0% 100.0% 100.0% 100.0% P=0.517 Total Positive patch test

Yes Count 49a 73a 47a 8a 177

% within age group

62.0% 71.6% 66.2% 47.1% 65.8%

No Count 30a 29a 24a 9a 92

% within age group 38.0% 28.4% 33.8% 52.9% 34.2% Total Count 79 102 71 17 269 % within age group 100.0% 100.0% 100.0% 100.0% 100.0% P=0.193

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Discussion of results

The growing interest about ACD in Kaunas Clinical Hospital has motivated me to evaluate the changes in Kaunas population in regards to an increased susceptibility to allergens and to evaluate the most prevalent allergen in Kaunas Clinical Hospital. During 2015, 2016 and 2017 there were a total of 269 patients that were patch tested, among them 217 (80.67%) patients were women, and 52 (19.33%) were men. The average age of male in the study was 39.7 (SD 17.05) years old while in the female it was 41.7 (SD 16.32) years old; there was not an

enormous between mean age in both genders. The SD of the study population was high thus indicating the data is spread out over a broader range, 41.7 (SD 16.45) years old in the overall study population. Age group 30 ≤ x ≤ 49 was found to be the most prominent group with the highest number of individuals who tested positive to a contact allergen in both genders, (respectively 42.31% in male and 36.87% in female).

Overall results indicated that women and men in Kaunas region are more susceptible to textile dye as shown in table 3, there were 74 (41.81%) individuals that resulted in a positive patch test result. The reason for an increase in susceptibility could be directly correlated to the dye used in fabric colouring and also as it is one of the vital components in finishing agents, flame-retardants and also there are numerous types in various application, acid, basic, direct, vat, disperse, reactive and sulfur. Thus, illustrates it could be linked to clothing or profession. The Nickel Mandate in Lithuania is embraced since 2002, while a sort of limitation in nickel presentation has been available in Sweden as of now since 1991 when nickel-containing piercers or rings were restricted if the composite contained over 0.05% nickel. (3) Nickel is the most common sensitizer in adults, and the frequency of sensitization varies from 10% to 32% (1,20). This had an impact on the prevalence of nickel, as it has become the second most prevalent contact allergen in my study, 46 (25.99%) showed hypersensitivity, though showed a majority of individuals were women. There was upward trend observed in the results of hypersensitivity to nickel, (respectively 1.69%, 8.47% and 15.81%). The 3rd most prevalent contact allergen in my study was found to be cobalt chloride (21.47%). Over the three years, it was found cobalt hypersensitivity was on the rise, (respectively 1.13%, 5.08% and 15.25%) Overall results indicated that women and men in Kaunas region are more susceptible to textile dye as shown in table 4. There were 58 (32.77%) female and 16(9.04%) male found to be prevalent. It was found 26.7% of female and 30.8% of the male from the study population to be hypersensitive. There was an upward trend found in the female population in all three

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years. From the three years results acquired it was found that women overall were more

hypersensitive to nickel, (respectively 5.8% male and 20.7% female), (p=0.011). Particular sex and age-related examples of nickel introduction, mostly by early ear piercing and the

following of wearing nickel-discharging adornments, well known among ladies at a younger age and was found to be the leading allergen in Lithuania, with the sex and age factors strongly influencing rate of sensitization. (8,21) There was a consecutive increase in all three years in the female population while there was no male hypersensitive in 2015 and 2016. There were 5.8% of the male population and 20.7% of the female from the study population of 269 allergic to nickel. Women under 40 years were found to be sensitive to nickel almost four times more often than older ones in a previous study (7). In Lithuania, the frequency of sensitization to nickel sulfate nearly doubled, from 16.4% in 2006–2008 to 30.6% in 2014– 2015. Nickel is a very common allergen in the group, age, and sex unequivocally affecting the pervasiveness of sensitization. These outcomes allude to sex-related and age-related examples of nickel presentation, early ear piercing, and contact with nickel-discharging jewelry.

Information from Finland and Poland Contact sensitivity focuses indicated sensitization rates to nickel of 21.3% and 24.3%, separately, in 2007-2008. The main ten allergens continued as before in the 9-year time frame aside from MI, which showed up in 2014 – 2015. There was no past data on contact sensitivity to MI in Lithuania, as MI was added to the European gauge arrangement in 2014 in Lithuania. (8) There were 12 (8.3%) positive reactions in women and 2 (5.7%) in men over the course of three years to MCI/MI. Fragrance mix one was found to be one of the common allergens in women, 24 (13.57%) resulted in a positive reaction and also showed an upward trend in my data indicating a rise in prevalence. A relationship with a more successive utilization of common prescription, which is connected to measurably noteworthy sensitization to fragrance mix I in older patients (8)

Overall 65.8% of the study populations resulted in positive patch test results and with confirmed contact hypersensitivity. Each year the proportion of positive patch test results increased in the study population. We evaluated the number of patients that were

monosensitive and polysensitive and found that there was a significant rise in patients with polysensitivity. Comparing the data obtained from the charts indicated an upward trend from 2015 and illustrated an increase in susceptibility. There were 92 (63.4%) women found to be polysensitive in comparison to 19 (59.4%) of men highly susceptible to polysensitization. Table 9 shows a growing trend in polysensitization as 111 (69.2%) of individuals positive patch tested. There was fluctuation in female and male population over 2015, 2016 and 2017

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concerning monosensitization. In 2015 monosensitization was most frequent among in young group of 10 – 29 years old, (p=0.002). Polysensitization was most frequent in the age group 30 ≤ x ≤ 49 years old (71.2% of patients were polysensitized). While in the age group 10 ≤ x ≤ 29 there were a total of 49 (62.0%) positive patch test results and in the age group 50 ≤ x ≤ 69 there was 47 (67.1%). while assessing the relationship between association in young people and grown-ups as the natural presentation time clearly is any longer in grown-ups and as the insusceptible reactivity may change with age or atopy.

We evaluated the age and gender correlation among the participants; it was found that there were significantly higher percentages of female and male contributors in the age group 30 < x <49. It was found that 39.3% women of this age group tested positive while 39.14% showed a negative reaction out of the total of 217 patients. The highest proportion of individuals with positive patch test was detected in the age group 30 ≤ x ≤49 years old (71.6% of patients of this age group), (respectively 72.7% in male and 71.3% in female). While in the age group 10 ≤ x ≤ 29 there were a total of 49 (62.0%) positive patch test results and in the age group 50 ≤ x ≤ 69 there was 47 (67.1%). While assessing the relationship between association in young people and grown-ups as the natural presentation time is any longer in adults and as the insusceptible reactivity may change with age or atopy.

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Conclusion

• Textile dye, nickel, and cobalt were the most prevalent contact allergens in this study population; the prevalence was observed respectively 32.77% and 24.3% and 21.47%.

• The most prevalent contact allergens among females were textile dye, nickel sulphate and cobalt chloride. The most prevalent contact allergens among male were textile dye, cobalt chloride and PPD. Women were found to be more hypersensitive to nickel sulphate in the study population in comparison to men (p=0.011).

• Overall 62.7% patients with positive patch test result were polysensitized. There was an upward trend in the proportion of females in 2017 with polysensitization than in previous two years (p > 0.05).

• Overall there were 65.8% of study populations with positive patch test results and there was no significant difference in test positivity according to gender. The highest proportion of individuals with positive patch test was detected in the age group 30 ≤ x ≤49 years old.

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Practical recommendations

• In women, avoidance of jewelry composed of nickel and restrain from ear piercing at very young age

• In both genders, educate yourself to fabric and finishing agents with composition of textile dye.

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