Frequency of sensitization to the individual fragrances of fragrance mix I and II according to the factors included in the MOAHLFA index.

BACKGROUND: Fragrances constitute the second most frequent cause of allergic contact dermatitis in Spain. OBJECTIVES: To determine the rate of sensitization to the individual fragrances of fragrance mix (FM) I and FM II for each of the demographic and clinical factors included in the MOAHLFA (male, occupational dermatitis, atopic dermatitis, hand dermatitis, leg dermatitis, facial dermatitis, age) index. METHODS: We conducted a 5-year retrospective study in 23 Spanish centres. We identified the patients who had undergone patch testing with a specific fragrance series after reacting positively to fragrance markers in a baseline series. We obtained the MOAHLFA index items in this population, then calculated for each demographic and clinical factor the frequencies of sensitization to the individual fragrances of FM I and FM II. RESULTS: A specific fragrance series was patch tested in 1013 patients. The most frequent allergens in men, women, children, and retired people were Evernia prunastri (16%), geraniol (16.6%), isoeugenol (17.9%), and geraniol (22.4%), respectively. Citral (20.5%) and hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC) (14.5%) were the most common allergens in occupational eczemas and were also associated with a large proportion of hand and facial dermatitis. CONCLUSIONS: Frequency of sensitization to the individual fragrances of FM I and FM II varies with age, sex, affected body region, and history of occupational or atopic dermatitis.

Sensitization to fragrances in Spain: A 5-year multicentre study (2011-2015).

BACKGROUND: Fragrance chemicals constitute the second most frequent cause of contact allergy in Spain. There are no data available concerning the individual fragrances that are most frequently involved. OBJECTIVES: To describe the diagnostic contribution provided by specific fragrance series to the results obtained with baseline series fragrance markers by correlating the results of both series. MATERIALS AND METHODS: We performed a 5-year retrospective study of fragrance marker-positive patients tested with specific fragrance series in 23 Spanish centres. We collected the demographic and clinical characteristics, and compared the results of patch tests obtained from different suppliers. RESULTS: Of 19 588 patients patch tested with the Spanish baseline series, 1590 (8.1%) reacted positively to a fragrance marker. Of these, 1013 (63.7%) were patch tested with a fragrance series, and 664 patients reacted positively to at least one individual fragrance other than hydroxyisohexyl 3-cyclohexene carboxaldehyde. Geraniol was the most frequent allergen. Positive reactions to substances not included in fragrance mix (FM) I or FM II were found in 230 patients. Of the 436 FM I-positive patients and the 419 FM II-positive patients, 184 (42%) and 64 (39.1%), respectively, had no positive reactions to fragrance series. In the case of FM I, negative results were more common when individual fragrances were patch tested at low concentrations. CONCLUSIONS: We recommend patch testing all patients positive for any fragrance marker with a specific fragrance series. The correlation between the results of baseline series and fragrance series could be improved by increasing the concentrations of individual fragrances.

Contact sensitization to limonene and linalool hydroperoxides in Spain: a GEIDAC* prospective study.

BACKGROUND: Limonene and linalool are common fragrance terpenes widely used in cosmetic, household and hygiene products. Their primary oxidation products formed after air exposure, the hydroperoxides, have been recognized as important contact haptens. OBJECTIVES: To investigate the prevalence of contact allergy to hydroperoxides of limonene (Lim-OOHs) and hydroperoxides of linalool (Lin-OOHs) in Spain, and to define the optimal concentration for screening in consecutive patients. METHODS: Three different concentrations of Lim-OOHs (0.1%, 0.2% and 0.3% pet.) and Lin-OOHs (0.25%, 0.5% and 1.0% pet.) were simultaneously tested in 3639 consecutive patients at 22 departments of dermatology in Spain. RESULTS: Lim-OOHs at 0.1%, 0.2% and 0.3% yielded positive patch test reactions in 1.4%, 3.4% and 5.1% of the tested patients, respectively; and Lin-OOHs at 0.25%, 0.5% and 1.0% yielded positive reactions in 1.3%, 2.9% and 4.9% of the tested patients, respectively. Few irritant (1.5-1.9%) and doubtful reactions (0.4-0.5%) to both terpene hydroperoxides were registered at the highest concentrations tested. CONCLUSIONS: Lim-OOHs and Lin-OOHs can be considered as common causes of contact allergy, and their inclusion in an extended baseline patch test series therefore seems to be appropriate. The patch test preparations of Lim-OOHs 0.3% pet. and Lin-OOHs 1.0% pet. are useful tools for screening of contact sensitization.

Oxidized limonene and oxidized linalool - concomitant contact allergy to common fragrance terpenes.

BACKGROUND: Limonene and linalool are common fragrance terpenes. Both oxidized R-limonene and oxidized linalool have recently been patch tested in an international setting, showing contact allergy in 5.2% and 6.9% of dermatitis patients, respectively. OBJECTIVE: To investigate concomitant reactions between oxidized R-limonene and oxidized linalool in consecutive dermatitis patients. METHODS: Oxidized R-limonene 3.0% (containing limonene hydroperoxides 0.33%) and oxidized linalool 6% (linalool hydroperoxides 1%) in petrolatum were tested in 2900 consecutive dermatitis patients in Australia, Denmark, Singapore, Spain, Sweden, and the United Kingdom. RESULTS: A total of 281 patients reacted to either oxidized R-limonene or oxidized linalool. Of these, 25% had concomitant reactions to both compounds, whereas 29% reacted only to oxidized R-limonene and 46% only to oxidized linalool. Of the 152 patients reacting to oxidized R-limonene, 46% reacted to oxidized linalool, whereas 35% of the 200 patients reacting to oxidized linalool also reacted to oxidized R-limonene. CONCLUSIONS: The majority of the patients (75%) reacted to only one of the oxidation mixtures, thus supporting the specificity of the reactions. The concomitant reactions to the two fragrance allergens suggest multiple sensitizations, which most likely reflect the exposure to the different fragrance materials in various types of consumer products. This is in accordance with what is generally seen for patch test reactions to fragrance materials.

Dermatitis Artefacta in Childhood: A Retrospective Analysis of 44 Patients, 1976-2006.

BACKGROUND: Dermatitis artefacta (DA) consists of self-inflicted skin lesions that the patient denies having produced. OBJECTIVES: To conduct a single-center retrospective clinical review of children and adolescents diagnosed with DA. METHODS: From 1976 to 2006, data were collected on children diagnosed with DA who were seen in the Department of Dermatology in our hospital. Clinical and epidemiologic features are described. Forty-four children (mean age 12.9 yrs) were selected, representing 21.9% of the total patients with DA recorded (n = 201) during this period. RESULTS: The most frequent clinical forms were excoriations (16 [36.4%]) and ulcers (10 [22.7%]), followed by blisters (7 [15.9%]), burns (3 [6.8%]), contact dermatitis (3 [6.8%]), hematomas (2 [4.5%]), panniculitis (1 [2.3%]), cheilitis (1 [2.3%]), and hyperpigmentation (1 [2.3%]). Sixteen were located exclusively on the face and neck, whereas 28 also had other locations (upper limbs, n = 10; lower limbs, n = 9; thorax, n = 5; abdomen, n = 4). Cutaneous lesions were treated with occlusive bandages using zinc paste or a plaster splint when necessary. CONCLUSION: To our knowledge, this is the largest reported series of DA in childhood. This complicated psychodermatologic condition requires correct diagnosis, appropriate management, and psychiatric assessment.

Positive patch test reactions to oxidized limonene: exposure and relevance.

BACKGROUND: R-Limonene is a common fragrance terpene found in domestic and industrial products. R-Limonene autoxidizes on air exposure, and the oxidation products can cause contact allergy. In a recent multicentre study, 5.2% (range 2.3-12.1%) of 2900 patients showed a positive patch test reaction to oxidized R-limonene. OBJECTIVE: To study the exposure to limonene among consecutive dermatitis patients reacting to oxidized R-limonene in an international setting, and to assess the relevance of the exposure for the patients' dermatitis. METHODS: Oxidized R-limonene 3.0% (containing limonene hydroperoxides at 0.33%) in petrolatum was tested in 2900 consecutive dermatitis patients in Australia, Denmark, the United Kingdom, Singapore, Spain, and Sweden. A questionnaire assessing exposure to limonene-containing products was completed. RESULTS: Overall, exposure to products containing limonene was found and assessed as being probably relevant for the patients' dermatitis in 36% of the limonene-allergic patients. In Barcelona and Copenhagen, > 70% of the patients were judged to have had an exposure to limonene assessed as relevant. CONCLUSIONS: Oxidized R-limonene is a common fragrance allergen, and limonene was frequently found in the labelling on the patients' products, and assessed as relevant for the patients' dermatitis. A large number of domestic and occupational sources for contact with R-limonene were identified.

An international multicentre study on the allergenic activity of air-oxidized R-limonene.

BACKGROUND: Limonene is a common fragrance terpene that, in its pure form, is not allergenic or is a very weak allergen. However, limonene autoxidizes on air exposure, and the oxidation products can cause contact allergy. Oxidized R-limonene has previously been patch tested in multicentre studies, giving 2-3% positive patch test reactions in consecutive patients. OBJECTIVES: To investigate whether oxidized R-limonene 3.0% in petrolatum, with a stable concentration of the main haptens, limonene hydroperoxides (Lim-OOHs), could be a useful tool for the detection of contact allergy in an international setting. METHODS: Oxidized R-limonene 3.0% (Lim-OOHs 0.33%) pet. was tested in 2900 consecutive dermatitis patients in Denmark, the United Kingdom, Singapore, Spain, Sweden, and Australia. RESULTS: Overall, 5.2% (range 2.3-12.1%) of the patients showed a positive patch test reaction to oxidized R-limonene. Doubtful reactions were found in 7.0% of the patients (range 0-24%). Few irritant reactions were seen. CONCLUSIONS: Oxidized R-limonene at 3.0% pet. with a specified content of Lim-OOHs 0.33% is a standardized and useful tool for the detection of contact allergy in dermatitis patients. Many patients showing positive patch test reactions to oxidized R-limonene would not be informed of their fragrance allergy if this specific test had not been performed.

Prevalence of autosomal recessive congenital ichthyosis: a population-based study using the capture-recapture method in Spain.

BACKGROUND: Previous reports on the prevalence of autosomal recessive congenital ichthyosis (ARCI) were based on single source data, such as lists of members in a patient association. These sources are likely to be incomplete. OBJECTIVES: We sought to describe the prevalence of ARCI. METHODS: We obtained data from 3 incomplete sources (dermatology departments, a genetic testing laboratory, and the Spanish ichthyosis association) and combined them using the capture-recapture method. RESULTS: We identified 144 living patients with ARCI. Of these, 62.5% had classic lamellar ichthyosis and 30.6% had congenital ichthyosiform erythroderma. The age distribution included fewer elderly patients than expected. The prevalence of ARCI in patients younger than 10 years, the best estimate as less subject to bias, was 16.2 cases per million inhabitants (95% confidence interval 13.3-23.0). According to the capture-recapture model, 71% of the patients were not being followed up in reference units, 92% did not have a genetic diagnosis, and 78% were not members of the ichthyosis association. LIMITATIONS: The prevalence of ARCI in Spain and findings related to the Spanish health care system might not be generalizable to other countries. CONCLUSIONS: The prevalence of ARCI is higher than previously reported. Many patients are not being followed up in reference units, do not have a genetic diagnosis, and are not members of a patient association, indicating room for improvement in their care. Data suggesting a reduced number of older patients might imply a shorter life expectancy and this requires further study.

Air-oxidized linalool: a frequent cause of fragrance contact allergy.

BACKGROUND: Linalool is a common fragrance terpene that, in pure form, is not allergenic or is a very weak allergen. However, linalool autoxidizes on air exposure, and the oxidation products can cause contact allergy. In a Swedish study, oxidized linalool 6.0% in petrolatum (pet.) gave 5% positive patch test reactions in 2500 dermatitis patients. OBJECTIVES: To investigate whether oxidized linalool 6%, with a stable concentration of the main haptens, the linalool hydroperoxides (Lin-OOHs) in pet., could be a useful tool for the detection of contact allergy in an international setting. Methods. Oxidized linalool 6.0% (Lin-OOHs 1%) pet. was tested in 2900 consecutive dermatitis patients in Denmark, the United Kingdom, Singapore, Spain, Sweden, and Australia. RESULTS: Overall, 6.9% (range 3-13%) of the patients showed positive patch test reactions to oxidized linalool. Doubtful reactions were found in 9.2% of the patients (range 0-36%). Few irritant reactions were seen. CONCLUSIONS: In an international setting, oxidized linalool has been shown to be a common allergen. Oxidized linalool 6.0% (Lin-OOHs 1%) pet. is a useful, standardized and stable tool for the detection of contact allergy in dermatitis patients. Many patients showing positive patch test reactions to oxidized linalool would not have been informed of their fragrance allergy if this specific test had not been performed.

Patch testing with formaldehyde and formaldehyde-releasers: multicentre study in Spain (2005-2009).

BACKGROUND: Formaldehyde and formaldehyde-releasers are common causes of allergic contact dermatitis. OBJECTIVES: To determine the frequency of sensitization to formaldehyde and seven formaldehyde-releasers. To establish and characterize groups of patients according to the results of patch testing. MATERIALS AND METHODS: We performed a 5-year retrospective study, in six Spanish hospitals, of patients with positive patch test reactions to formaldehyde or any of seven formaldehyde-releasers. RESULTS: The most frequent allergens were formaldehyde (1.72%), imidazolidinyl urea (1.05%), quaternium-15 (0.88%), and diazolidinyl urea (0.79%). Patients with sensitization to only formaldehyde had a higher frequency of occupational dermatitis (25%) than patients with sensitization to only formaldehyde-releasers (9.5%). The most common sites of dermatitis were the hands (31.7%) in patients with sensitization to only formaldehyde and the face and legs (31.3% and 24.6%) in patients with sensitization to only formaldehyde-releasers. We found a subgroup of 25 patients who were sensitized to both imidazolidinyl urea and diazolidinyl urea, and only 6 of these (24%) were also sensitized to formaldehyde. CONCLUSIONS: The inclusion of imidazolidinyl urea and diazolidinyl urea in the baseline series of the Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC) should enable better classification of patients allergic to formaldehyde, and could aid in their management.

Patch testing in children with hand eczema. A 5-year multicentre study in Spain.

BACKGROUND: Hand eczema is common in children, but affected children are seldom patch tested. Relatively few studies have assessed patch testing in the paediatric population, and none has specifically evaluated its use in hand eczema in children. OBJECTIVES: The aim of this study was to determine the prevalence of contact allergy in children with hand eczema, and to identify the most frequent allergens and their relevance. MATERIAL AND METHODS: We performed a 5-year retrospective study of children (aged 0-15 years) with hand eczema tested with the Spanish baseline series at the Dermatology Departments of 11 Spanish hospitals. RESULTS: During the study period, 11 729 patients were patch tested, of whom 480 were children. Hand eczema was present in 111 (23.1%) of the children and in 3437 (30.5%) of the adults. Of the children with hand eczema, 46.8% had at least one positive reaction in the patch tests. Current relevance was found for 78% of the allergens detected. The most common allergens were nickel sulfate, methylchloroisothiazolinone/methylisothiazolinone, and fragrance mix I. Allergic contact dermatitis was the most frequent diagnosis (36%), followed by atopic dermatitis. CONCLUSIONS: Allergic contact dermatitis was the most usual diagnosis in our series of children with hand eczema. We recommend patch testing of all children with chronic hand eczema, as is already performed in adults.

Riga-Fede disease associated with postanoxic encephalopathy and trisomy 21: a proposed classification.

We present a new instance of Riga-Fede disease in a 2-year-old boy with Down syndrome and postanoxic encephalopathy. We propose a classification of the disease, as either "precocious," associated with natal or neonatal teeth or "late-onset," associated with neurologic disease.

Clinical and molecular study of the extracellular matrix protein 1 gene in a spanish family with lipoid proteinosis.

BACKGROUND: Lipoid proteinosis (LP) is a rare autosomal recessive disorder characterized by a hoarse voice, variable scarring, and infiltration of the skin and mucosa. This disease is associated with mutations of the gene encoding extracellular matrix protein 1 (ECM1). CASE REPORT: This was a clinical and molecular study of a new case of LP with a severe phenotype. A 35-year-old female born to nonconsanguineous parents developed dermatological and extracutaneous symptoms in her 9th month of life. The neurological abnormalities of the disease began to appear at the age of 19 years. Computed tomography revealed cranial calcifications. CONCLUSIONS: The diagnosis of LP was confirmed by histopathological findings and direct sequencing of ECM1. A new homozygous nonsense mutation was identified in exon 7 of ECM1, c.1076G>A (p.Trp359(*)). This mutation was not detected in 106 chromosomes of healthy individuals with a similar demographic origin. Microsatellite markers around ECM1 were used to construct the haplotype in both the parents and the patient. Reports on genotype-phenotype correlations in LP point to a milder phenotype in carriers of missense mutations in the Ecm1a isoform, whereas mutations in the Ecm1b isoform are thought to be associated with more severe phenotypes. The present findings in a Spanish patient carrying a truncating mutation in exon 7 revealed complete dermatological and neurological manifestations.

[Generalized eczema secondary to combined treatment with peginterferon alfa-2a and ribavirin in a patient with chronic hepatitis from the hepatitis C virus]. / Eczema generalizado secundario a tratamiento combinado con interferón alfa-2a pegilado y ribavirina en un paciente con hepatitis crónica por virus de la hepatitis C.

Adverse skin effects from interferon (IFN) plus ribavirin combined therapy are relatively frequent, but they are usually local and related to the IFN injection site. However, distant or generalized eczematous reactions secondary to this treatment are rare. The introduction of pegylated interferons may increase the frequency of these skin lesions.

Baboon syndrome in childhood: easy to avoid, easy to diagnose, but the problem continues.

Baboon syndrome was first described as a particular type of systemic contact dermatitis, characterized by an exanthem with involvement of the buttocks and flexures. In children, it is an important entity to take into account for the differential diagnosis of viral exanthem. A large number of allergens have been implicated, although inhalation of mercury vapor is a common trigger. We present the findings in 14 patients younger than 14 years with baboon syndrome. We also look at the frequency in children and the most common causes and triggers in our area.

Oxidized citrus oil (R-limonene): a frequent skin sensitizer in Europe.

BACKGROUND: Peel oil from citrus fruits consists of R-(+)-limonene, which is one of the most commonly used fragrance materials in technical products and in fine fragrances. This substance forms allergenic oxidation products during handling and storage. OBJECTIVE: We wanted to study the frequency of allergic reactions to oxidized R-(+)-limonene in patients with dermatitis and find a suitable test preparation. METHOD: Patch testing with oxidized R-(+)-limonene was performed on 2273 patients at 4 dermatology clinics in Europe. RESULTS: Of the consecutive patients tested, 3.8% to 3.9% had positive reactions in two of the clinics; 6.5% had positive reactions in the third clinic; and 0.3% had positive reactions in the fourth clinic. A total of 63 patients showed positive reactions. In total, 57% of the patients did not react to fragrance mix or balsam of Peru. We recommend testing with 3% oxidized R-(+)-limonene in patients referred for patch testing. CONCLUSION: The high frequency of oxidized limonene allergy provides clinical evidence for the European classification of R-(+)-limonene that contains oxidation products as skin sensitizers.

Patch testing with oxidized R-(+)-limonene and its hydroperoxide fraction.

R-(+)-Limonene is an ubiquitous allergen in our environment. It is one of the most widely used fragrance materials not only in fine fragrances but also most often incorporated in domestic and occupational products. Although the non-oxidized R-(+)-limonene itself is not allergenic, it easily forms allergenic products due to autoxidation during handling and storage. 2273 patients at 4 dermatological clinics in Europe were patch tested between 1997 and 1999 in 2 steps. First, the oxidation mixture of R-(+)-limonene and 1 selected allergen fraction of the mixture, the limonene hydroperoxides, were tested in 2 different vehicles in consecutive patients. A diverging frequency of positive patch test reactions was observed in the 4 clinics. 3.8% of the consecutive patients tested reacted to oxidized R-(+)-limonene in 2 clinics, 6.5% in the 3rd, whereas 0.3% in the 4th clinic. In 2 of the centres, different but significant concomitant positive response rates to other allergens were observed; e.g. to fragrance materials and to colophonium. However, in the total test population, 57% of the limonene-allergic subjects did not react to any of the fragrance allergy markers used in the standard series. In the 2nd step, patients showing positive reactions were retested, also including additional separate allergens of the limonene oxidation mixture (carvone and limonene oxide). 60% of the limonene-allergic patients showed positive results at retesting. The limonene hydroperoxide fraction was proved to be the most important allergen of the oxidation mixture, showing positive reactions in around 60% of the limonene-allergic patients at both test sessions. Testing limonene oxide and carvone separately resulted in very few positive reactions. 3% oxidized R-(+)-limonene in non-stabilized petrolatum is most suitable when using only 1 test preparation for diagnosis of contact allergy to oxidized limonene. Our data give clinical support to the European classification of R-(+)-limonene, containing oxidation products, as a skin sensitizer.