Neomycin: sources of contact and sensitization evaluation in 1162 patients treated at a tertiary service

BackgroundNeomycin is used in several over-the-counter pharmaceutical formulations in Brazil. In Europe and Canada, where it is not freely available, its sensitization frequency is lower than in the United States, where this does not occur.ObjectiveTo present the frequency of sensitization to neomycin observed in a tertiary hospital and the pharmaceutical formulations sold in Brazil containing neomycin.MethodRetrospective analysis of positive results to neomycin, obtained through patch tests performed in a tertiary hospital, from 2009 to 2018 and investigation of topical drugs and vaccines containing neomycin in Brazilian databases available on the internet.ResultsAmong 1,162 patients, 71 (6%) had positive reactions to neomycin, 65% female and 35% male individuals, 46% were over 50 years old, and 24% had a personal history of atopy. The dermatitis lasted from four months to 20 years. Lesions were located in 69% of the patients on the upper limbs, in 55% they were on the lower limbs, and in 42% they were disseminated in more than 4 sites. Polysensitization was detected in 55% of cases. Of these, 28% were linked to sensitization to rubber allergens and 27% to potassium bichromate. A total of 158 topical presentations of neomycin were found: 79 ointments, 58 creams, 10 ophthalmic solutions, seven otological solutions, one oral solution, two nasal solutions, and one antiseptic powder, in addition to 11 types of vaccines.Study limitationsRetrospective study.ConclusionSensitization to neomycin occurred in 6% of the studied population, affecting more females aged over 50 years, with skin lesions located mainly on the upper and lower limbs, in the context of chronic contact dermatitis. Neomycin was found in 135 formulations, most of them available over the counter, as well as in 11 miscellaneous vaccines.     

The European baseline series in Lithuania: results of patch testing in consecutive adult patients

Background In Lithuania, data on patch testing are lacking and the applicability of the European baseline series needs to be evaluated. Objective The aim of the study was to examine the prevalence of contact allergy to the European baseline series in the population of patients with suspected allergic contact dermatitis in Lithuania. Methods Between April 2006 and October 2008, 816 consecutive adult patients referred to the Department of Skin and Venereal Diseases, Kaunas University of Medicine, with suspected allergic contact dermatitis were patch tested with the European baseline series. Demographic data were collected in accordance with the European Surveillance System on Contact Allergies ‘minimal data set’. Results The positive patch test was observed in 384 (47.4%) patients. The most prevalent contact allergens were nickel sulphate (17.1%), Myroxylon pereirae resin (8.0%), p‐phenylenediamine (6.0%), methyldibromo glutaronitrile (5.5%) and colophonium (5.0%). The sex and age factors strongly influenced the prevalence of nickel sensitization. The lowest sensitization prevalences were found to N‐isopropyl‐N′‐phenyl‐p‐phenylene diamine (0.1%) and 2‐mercaptobenzothiazole (0.1%). Differences in the sensitization prevalences to some allergens of the European baseline series compared with other European countries were recognized. Conclusion The current European baseline series is a suitable diagnostic tool for contact allergy in Lithuania.     

Allergen change in stasis dermatitis *

Stasis dermatitis of the lower leg is very often complicated by secondary contact allergy. A comparison of seven reported studies with our recent personal series of 118 cases revealed a difference in the incidence of sensitization between 39.5–90.5 %, due to selection for clinical reasons. The true incidence of contact allergy lies between 50–60 %. The importance of the individual allergens is nevertheless changing. In the last 10 years neomycin allergy has doubled; gentamycin has become an important primary allergen rather than a cross reactor.     

Twenty‐five years quaternium‐15 in the European baseline series: does it deserve its place there?

For allergens to be included in the European baseline series, they should have allergy rates of at least 1%. In several studies quaternium‐15 had lower scores. Also, many cases of sensitization are already detected by formaldehyde contact allergy. The aim of this study was to evaluate whether quaternium‐15 deserves continued inclusion in the baseline series on the basis of current criteria: 1% positive reactions, common occurrence in the environment, many relevant reactions. We used the literature survey method in this study. Only the United Kingdom has rates consistently over 1%. The mean for all other countries together and for many individual nations is lower than 1%. At least half of the reactions are already detected by formaldehyde sensitivity, which lowers rates for allergy to quaternium‐15 per se (i.e. not caused or at least detected by formaldehyde sensitivity) to less than 0.6% for all countries except the United Kingdom. Neither common occurrence in the environment nor a high percentage of relevant reactions has been ascertained. It may well be argued that quaternium‐15 does not deserve its place in the European baseline series and could be incorporated in a cosmetic screening series or preservative series instead. In the United Kingdom, routine testing should be continued.     

The coumarin herniarin as a sensitizer in German chamomile [Chamomilla recutita (L.) Rauschert,Compositae]

Background: Although German chamomile (Chamomilla recutita) is considered a weak sensitizer, recent studies have shown several possible non‐sesquiterpene lactone allergens in tea (infusions) from the plant. Objective: The aim of this study was to report the results of patch testing with herniarin (7‐methoxycoumarin), which is one of the possible coumarin allergens in chamomile. Patients/materials/methods: Between 1991 and 2009, selected patients with known or suspected Compositae contact allergy were patch tested with herniarin 1% petrolatum. Results: Among 36 patients tested, there was one positive and three doubtful positive reactions to herniarin. All 4 patients had a relevant contact allergy to German chamomile, whereas the majority of the remaining 32 patients had chamomile allergy of unknown relevance. Conclusions: The clinical results suggest that herniarin indeed is one of the non‐sesquiterpene lactone sensitizers in German chamomile and that sensitization may occur through, for example, external use of chamomile tea or use of chamomile‐containing topical herbal remedies.     

Epidemiología de la dermatitis de contacto: prevalencia de sensibilización a diferentes alérgenos y factores asociados

BackgroundIn clinical practice, contact dermatitis is a relatively common skin complaint, whose prevalence has increased in recent years. Study by patch testing is essential for diagnosis of contact sensitization.ObjectivesTo study the prevalence of sensitization to different allergens in a standard battery and observe the influence of different epidemiological and clinical variables on contact sensitization. A large number of allergens were included in our battery in order to detect new sensitizations whose prevalence might justify further study.Material and methodsThis was a retrospective, observational, epidemiological study of 1092 patients, conducted in our skin allergy unit between January 1, 2000, and December 31, 2005. All patients were studied with a battery of 51 allergens. We assessed the following variables: sex, age, type of referral, occupation, site and course of skin lesions, personal and family history of atopy, positive patch tests, clinical significance, diagnosis, source of sensitization, and occupational relationship.ResultsAt least 1 positive result was found in 55% of the patients, and 55.7% presented atopic dermatitis in one of its clinical variants: allergic contact dermatitis (28.2%), irritant contact dermatitis (20.1%), photoallergic contact dermatitis (2.2%), and phototoxic contact dermatitis (1.2%). The most prevalent allergens were nickel sulfate (29.3%), palladium chloride (11.7%), cobalt chloride (10.8%), potassium dichromate (7.5%), fragrance blends (6.3%), and p-phenylenediamine (6.1%).A positive occupational relationship was found in 41.1%, and 21.3% of the patients studied were diagnosed with occupational contact dermatitis. Metalworkers, construction workers, and professional hairdressers were the most strongly represented groups. The most common source of sensitization was contact with metallic objects, followed by drugs, cosmetics, and rubber items. Female sex was the only independent variable that had a significant influence on the risk of contact sensitization in general.ConclusionWomen became sensitized at a younger age than men, and the frequency of positive results in the patch tests increased with age, reaching a maximum at between 60 and 69 years of age, when the greatest rate of sensitization occurred. Comparison of our results with other Spanish data showed a progressive and constant increase in sensitization to nickel sulfate, fragrance blends, balsam of Peru, and rosin, and a decrease in sensitization to potassium dichromate. The inclusion of new allergens such as palladium chloride, diallyl disulfide, and p-toluene sulfonamide formaldehyde improved the sensitivity of the standard battery in the detection of contact sensitization. We therefore recommend further studies of these allergens.     

Contact sensitivity in patients with venous leg ulcers in Serbia: comparison with contact dermatitis patients and relationship to ulcer duration

Background: Contact hypersensitivity is a common occurrence in patients with chronic venous leg ulcers (CVLU) with allergen profiles depending upon the local treatment policies.
Objective: This study was to determine the frequency of contact sensitivity, prevalence of individual allergens, polyvalent sensitization, and/or their relationship to ulcers duration in the population of CVLU and contact dermatitis patients in Serbia.
Patients: 75 patients with CVLU and 82 patients with clinically suspected contact dermatitis were prospectively included in the study. The patients were patch tested with a series of 21 standard and 22 supplemental allergens.
Results: 73% ( n  = 55) of CVLU and 52% ( n  = 43) of control subjects had 1 or more positive patch test results ( P  < 0.01). Polysensitization was found in 53% of patients and 21% of controls ( P  < 0.01). CVLU patients run 2.5 and 4.3 higher risk for contact sensitization and polysensitization, respectively. The most common allergens were Balsam of Peru (21.3%), carba mix (18.7%), fusidic acid (17.3%), colophony (13.3%), paraben mix (12%), chloramphenicol (12%), silver nitrate (12%), and neomycin (10.7%). Polivalent sensitization and higher mean number of allergens were associated with ulcer duration >5 years.
Conclusions: The results confirm a high rate of contact (poly)sensitization in patients with CVLU and local variability in allergen prevalence.     

Fragrance contact allergy in Iran

Background Fragrances are considered as one of the most common causes of allergic contact dermatitis. About 1–4% of the general population suffer from fragrance contact allergy (FCA). Objectives To determine the frequency of FCA and its clinical relevance in a sample of Iranian patients with history of contact and/or atopic dermatitis from January 2004 to December 2008. Methods Standardized patch testing with 28‐allergen screening series recommended by the German Contact Dermatitis Research Group and European Standard Series was used at six dermatological clinics in Iran. Fragrance allergens comprised of fragrance mix I (FM I), Myroxylon pereirae (MP; balsam of Peru), Lyral^®, turpentine and FM II. Results Fragrance contact allergy was detected in 7.2% of the patients. The frequency of positive reactions to FM I, MP and FM II were 3.7% (41/1105), 2.8% (32/1135) and 1.1% (3/267) respectively. 82.4% of the reactions to fragrance allergens were clinically relevant. The most common involved areas were hands (68.4%) and face (35.4%). Fragrance allergy predominantly affected women aged more than 40 years (P = 0.008). Positive reaction to more than two allergens was significantly higher in FCA patients compared with other contact dermatitis patients (P < 0.0001), and FM I, nickel and MP were the most frequent allergens in these patients. Conclusions Despite less frequency of FCA in comparison with some European countries, its clinical relevance in Iranian patients seems to be high. It mostly affects the hands and the face predominantly in women aged more than 40 years.     

Frequency of contact allergy in children with atopic dermatitis: results of a prospective study of 137 cases

The aim of our study was the evaluation of contact sensitization in pediatric patients with atopic dermatitis (AD). It seems that the frequency of contact allergies in the course of AD, and also the frequency of contact allergies in children, is underestimated in general. Our study has been performed by investigating 137 children with AD. The childrens' history was taken according standardized consultation guidelines and followed by a physical examination. Patch testing was performed systematically, including the European standard series, together with tixocortol pivalate, budesonide and the applied emollient. If necessary, optional patch tests were performed according to the child's history. The results demonstrate contact sensitization in 43% of all children tested. The most frequent contact allergens are: metals (19.3%), fragrance (4.4%), balsam of Peru (2.6%), lanolin (4.4%), neomycin (2.6%) and emollients (2.6%). No contact sensitization to corticosteroids nor any induction of active sensitization were seen. Statistical analysis demonstrates that the risk of developing a contact allergy is significantly elevated in children after the age of 5 years. Female sex is a risk factor only for nickel. Age of onset of AD or its severity is not associated with the development of contact allergy. In conclusion, the results indicate the necessity of performing systematic patch testing in the investigation of allergies in children with AD. Preventive measures from an early age are suggested to avoid exposure to the most frequent contact allergens.     

Epidemiology of contact dermatitis in Spain. Results of the Spanish Surveillance System on Contact Allergies for the year 2008

BackgroundThe epidemiology of contact dermatitis can be analyzed using clinical data from skin allergy units.ObjectivesThe aims of this study were to define the profile of patients attending a skin allergy unit and to determine the prevalence of the most common sensitizations in this population.Material and methodsThroughout 2008, a retrospective observational study was carried out in the 5 hospitals of the Spanish Surveillance System on Contact Allergies. All patients underwent skin patch tests with the Spanish standard series. The frequencies of sensitization were normalized for age and gender.ResultsData were gathered on 1161 patients. The 5 allergens that gave the most frequent positive reactions were nickel sulfate (25.88%), potassium dichromate (5.31%), cobalt chloride (5.10%), fragrance blends (4.64%), and balsam of Peru (4.44%). The least frequently detected reactions were to quinolone–clioquinol mix and sesquiterpene lactone mix. There was a 35% prevalence of sensitization to nickel among women.ConclusionsThe profile of sensitizations in Spain is similar to that of other Southern European countries. Nickel sulfate continues to be the most prevalent allergen, particularly in women. The low prevalence of sensitization to quinolone–clioquinol mix and sesquiterpene lactone mix supports their exclusion of the Spanish series.     

Guinea pig maximization test open epicutaneous test and chamber test in induction of delayed contact hypersensitivity

A comparison was made between the guinea pig maximization test (GPMT), open epicutaneous rest (OET) and chamber test (CT), and the allergens were neomycin sulphate and propylene glycol (PG). The sensitization rate for neomycin in petrolatum was 35 % in GPMT, 25 % in OET and 25 % in CT. The corresponding figures for neomycin in PG were 30 % in GPMT, 45 % in OET and 32 % in CT. PG caused no hypersensitivity in 118 guinea pigs. The results suggested that as a hygroscopic, irritant and penetrating vehicle, PG facilitates the induction of delayed contact allergy, especially in OET.     

The frequency of contact allergy in children and adolescents in the Czech Republic

The objective of our study was to determine the prevalence of contact hypersensitivity in asymptomatic Czech schoolchildren. We recruited 236 Prague asymptomatic schoolchildren for epicutaneous tests. The children were tested with European baseline series (25 allergens). A total of 218 children (114 boys and 104 girls) completed the study. Of these, 67 (30.7%) children had one or more positive reactions to tested allergens. Nickel, neomycin and potassium dichromate were the most prevalent allergens detected in our study. Our findings may support the notion that allergic contact sensitization in children is not so rare and children, especially those with chronic dermatitis, should be patch tested regularly.     

Contact dermatitis in hairdressers: Patch test results in 379 hairdressers (1980–1993)

From 1980 to 1993, 379 hairdressers were studied in the outpatient clinic of our department. All were patch tested with a standard screening tray and specific hairdressing products. Most of the workers assessed were women (92.3%) with a mean age of 21.33 years. A positive patch test response to one or more of the allergens tested was presented by 58.8%. Allergic contact dermatitis was diagnosed in 48.8%. The mean frequencies of sensitization ranked as follows: p-phenylenediamine base, 45.9%; nickel, 41.4%; disperse orange 3, 32.7%; and 4-aminoazobenzene, 31.9%. Finally, the risk of contact dermatitis is indicated among these workers and their sensitization, while still young, after only a few years in the trade.     

Does airborne nickel exposure induce nickel sensitization?

Background and objective: Nickel is one of the most prevalent causes of contact allergy in the general population. This study focuses on human exposure to airborne nickel and its potential to induce allergic sensitization. Materials and methods: The study group consisted of 309 children at school‐starter age living in the West of Germany in the vicinity of two industrial sources and in a rural town without nearby point sources of nickel. An exposure assessment of nickel in ambient air was available for children in the Ruhr district using routinely monitored ambient air quality data and dispersion modelling. Internal nickel exposure was assessed by nickel concentrations in morning urine samples of the children. Results: The observed nickel sensitization prevalence rates varied between 12.6% and 30.7%. Statistically significant associations were showed between exposure to nickel in ambient air and urinary nickel concentration as well as between urinary nickel concentration and nickel sensitization. Furthermore, an elevated prevalence of nickel sensitization was associated with exposure to increased nickel concentrations in ambient air. Conclusion: The observed associations support the assumption that inhaled nickel in ambient air might be a risk factor for nickel sensitization; further studies in larger collectives are necessary.     

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 review of 241 subjects who were patch tested twice: could fragrance mix I cause active sensitization?

BACKGROUND: Active patch test sensitization is an uncommon phenomenon which may have undesirable consequences for those undergoing this gold-standard investigation for contact allergy. OBJECTIVES: To perform a retrospective analysis of the results of 241 subjects who were patch tested twice in a monocentre evaluating approximately 1500 subjects per year. METHODS: Positivity to 11 common allergens in the recommended Baseline Series of contact allergens (European) was analysed: nickel sulphate; Myroxylon pereirae; fragrance mix I; para-phenylenediamine; colophonium; epoxy resin; neomycin; quaternium-15; thiuram mix; sesquiterpene lactone mix; and para-tert-butylphenol resin. RESULTS: Only fragrance mix I gave a statistically significant, increased rate of positivity on the second reading compared with the first (P=0.011). This trend was maintained when separately analysing a subgroup of 42 subjects who had been repeat patch tested within 1 year; this analysis was done to minimize the potential confounding factor of increased usage of fragrances with a wide interval between both tests. To reduce the confounding effect of age on our data, we calculated expected frequencies of positivity to fragrance mix I based on previously published data from our centre. This showed a marked excess of observed cases over predicted ones, particularly in women in the age range 40-60 years. CONCLUSIONS: We suspect that active sensitization to fragrance mix I may occur. Similar published analysis from another large group using standard methodology supports our data.     

The epidemiology of contact allergy in the general population--prevalence and main findings

A substantial number of studies have investigated the prevalence of contact allergy in the general population and in unselected subgroups of the general population. The aim of this review was to determine a median prevalence and summarize the main findings from studies on contact allergy in the general population. Published research mainly originates from North America and Western Europe. The median prevalence of contact allergy to at least 1 allergen was 21.2% (range 12.5-40.6%), and the weighted average prevalence was 19.5%, based on data collected on all age groups and all countries between 1966 and 2007. The most prevalent contact allergens were nickel, thimerosal, and fragrance mix. The median nickel allergy prevalence was 8.6% (range 0.7-27.8%) and demonstrates that nickel was an important cause of contact allergy in the general population and that it was widespread in both men and women. Numerous studies demonstrated that pierced ears were a significant risk factor for nickel allergy. Nickel was a risk factor for hand eczema in women. Finally, heavy smoking was associated with contact allergy, mostly in women. Population-based epidemiological studies are considered a prerequisite in the surveillance of national and international contact allergy epidemics.     

Unexpected sensitization routes and general frequency of contact allergies in an elderly stented Swedish population

Contact allergy to stent material has been proposed to be a risk factor for restenosis, after percutaneous transluminal coronary angioplasty (PTCA) and stenting. Information on the general frequency of contact allergy in the elderly population is scarce and knowledge of possible sensitization routes is important to investigate. The aim of this study was to investigate contact allergy to stent materials and other allergens. Here we report our findings on the frequency of contact allergies apart from those from stent material. In this retrospective study, we patch tested an elderly population, treated with PTCA and stented, with our standard series. A dermatitis population served as controls. We found a high frequency of contact allergy in both groups but a greater 'contact allergy burden', with generally higher frequencies for contact allergens, in the dermatitis patients as expected. Myroxylon pereirae and caine mix were apart from metals exceptions with statistically significant higher frequencies (P < 0.01) for the stented patients. Contact allergy to nonmetal sensitizers is common in an elderly Swedish stent population although, on the whole, substantially less than in an age and sex-matched dermatitis population. The findings indicate the importance of the oral mucosa for sensitization. In a general population that has been treated with a special medication/treatment procedure, contact allergies not suspected (such as to M. pereirae and to the metals) might suddenly peak. This underlines the importance of a careful evaluation of new products and routines with regard to contact allergies in the population.     

Nickel,cobalt and chromate sensitization and occupation*

Background: Exposure to nickel, cobalt and chromate are important causes of occupational contact dermatitis. Objectives: To estimate the prevalence of nickel, cobalt and chromate allergy in a population of consecutive patients and to investigate the possible association with individual and occupational risk factors. Patients/Methods: A total of 14 464 patients (67.6% women and 32.4% men) with suspected allergic dermatitis underwent patch tests. The associations between patch test results and occupations were studied by multivariate logistic regression analysis. Results: About 24.6% of the patients reacted positively to nickel sulphate, 10.2% to cobalt chloride and 8.7% to potassium dichromate. Nickel sensitization was higher in women aged 26–35 years in comparison with the youngest group (15–25 years) and the older group (> 45 years). In women, the prevalence of positive reactions to nickel was positively associated with metal and mechanical work (OR 1.54; 95%, CI 1.16–2.05). Chromate sensitization was more prevalent in building trade workers for both women (OR 1.58; 95% CI 1.00–2.49) and men (OR 2.24; 95% CI 1.55–3.22). Cobalt sensitization was associated with textile and leather work in women (OR 1.52; 95% CI 1.09–2.12) and with cleaning work in men (OR 1.86; 95% CI 1.18–2.93). Conclusions: Our study showed interesting associations between some occupations and nickel, chromate and cobalt allergy.