Integrins Are Required for Langerhans Cell Migration From the Epidermis
Objective.—In mice exposed to topical allergens, epidermal Langerhans cells (LCs) migrate from the skin to accumulate as immunostimulatory dendritic cells (DCs) in draining lymph nodes. Previous studies have suggested that the process of LC maturation and migration may involve cytokines derived from the epidermal cells; however, the possible role of adhesion molecules in LC migration has not been addressed. The integrins are a large family of cell surface adhesion receptors that serve as important receptors for adhesion to extracellular matrix proteins. The role of inte- grin-mediated interactions in regulating LC migration from the epidermis to the lymph nodes was studied.
Methods and Findings.—The study used blocking antibodies and pep-tides to assess the integrin-mediated interactions with laminin and fibronectin, 2 major components of the basement membrane and extracellular matrix. Seventy percent of LCs were found to express the as subunit, whereas no α6 integrin expression was noted for DCs. Expression of the α4 integrin subunit was much greater for DCs than for LCs. In both in vitro and in vivo studies, LC migration from skin was blocked by GoH3, an anti-Oj antibody that blocks binding to laminin. After topical application of a chemical allergen, GoH3 reduced lymph node accumulation of DCs by up to 70%. After GoH3 treatment, the LCs that remained in the epidermis showed a rounded appearance rather than the typical interdigitating morphological features; thus, the cells appeared to have detached from keratinocytes and prepared for migration but had been unable to exit the epidermis.
Treatment with PS/2, an anti-α4 integrin antibody that blocks binding to fibronectin, did not alter LC migration either in vitro or in vivo. Neither did this antibody have any effect on DC accumulation in the lymph nodes after allergen administration. Experiments using Arg-Gly-Asp-containing peptides also showed no effect on LC migration from skin. α4 Integrins had no effect on DC accumulation in lymph nodes.
Conclusions.—This study documents the expression of α6 and β4 integrin subunits on murine LCs. It also shows that α6 integrins are directly regulators of LC migration from the epidermis. Migration of LCs is blocked by the and-as integrin antibody GoH3, which also blocks the interaction of α6β1, and α6β4 integrins with laminin.
- Price et al. provide compelling evidence that the afferent limb (i.e., LCs), of the immune response in allergic contact hypersensitivity requires integrins for functionality. In the authors’ experimental model, α6 integrin subsets, which bind to laminin, are necessary for antigen presentation by LCs. LCs whose a6 subunits are blocked fail to develop the typical morphological features for antigen presentation within the skin and do not migrate to regional lymph nodes; therefore, the afferent limb of the immune response for contact hypersensitivity is blocked. This finding, therefore, provides an additional mechanism whereby contact hypersensitivity could be managed by pharmacologic intervention.
Acute Irritant Contact Dermatitis: Recovery Time in Man
Introduction.—It can be difficult to determine the recovery time for complete healing of irritant contact dermatitis (ICD). Criteria for complete healing include normal function (i.e., loss of skin irritability, clinically normal skin) and normal results on quantitative testing. Using an irritant provocation method, the recovery time of augmented reactivity to a model surfactant was studied.
Methods.—Participants included 18 healthy adult volunteers. Each individual had acute ICD induced on his or her upper arm by occluded application of 1 % sodium lauryl sulfate (SLS) for 24 hours. Provocation of both previous ICD sites and normal sites was repeated at 2, 3, or 4 weeks using SLS concentrations of 2% or 7.5% for 30 min/day on 4 consecutive days. Daily evaluations of skin reactivity were performed, including visual erythema scoring, transepidermal water loss, skin color reflectance, and electrical capacitance.
Results.—In previous ICD sites, all measures of skin function did not return to normal until 2 weeks after provocation. By 3 weeks, all parameters had normalized. On subsequent provocation with SLS, there were significant differences in irritant reactivity, particularly with the 7.5% concentration. By 4 weeks, there were no significant differences between the previous ICD and normal sites.
Conclusions.—Long-lasting skin irritation occurred in response to a model irritant, even when skin function parameters appeared normal. The results suggest that it takes about 4 weeks to achieve complete recovery of skin function, including irritability, after acute experimental ICD. Thus skin that has been irritated should be protected from further irritant contact for several weeks, even if it appears normal. More study is needed to determine whether different chemical irritants produce a similar response.
- This study by Lee et al. attempts to define the recovery time in skin after acute ICD. They studied human skin irritated in an experimental setting and attempted to define its return to normal by measuring parameters including transepidermal water loss, capacitance, skin color reflectance, and visual erythema. They demonstrate that, at least experimentally, prolonged reactivity lasting up to 4 weeks can be demonstrated in previously irritated skin. They propose that after an acute irritant dermatitis, there may be subclinical irritation that persists beyond the evident changes. While it is not yet known how we can generalize these results to the clinical setting, it should, perhaps, cause us to consider protecting previously irritated skin even when it appears normal.
Estimating Dilutions for Patch Testing Skin Care Products: A Practical Method
Background.—The use of the patient’s own topical products is helpful for patch testing. However, the viscosity of the product can prevent easy measurement for dilution. A method for estimating volume:volume dilutions was presented.
Technique.—The clinician first chooses the dilution for the material to be prepared for patch testing. Then he or she draws up the indicated amount of water or gentian violet by pipette into a medicine cup. In a separate cup, the clinician visually matches the water or gentian violet drop size with a sample of material to be tested. Incremental amounts of the sample material can be added to the cup with the wooden end of a cotton-tip applicator. Water or petrolatum is then added to make 10 mL by matching the measuring line on the side of the cup containing the sample. The clinician mixes it well with the wooden end of a cotton-tip applicator. The clinician then applies 15 pL of liquid mixture to a disk or a 5 mm ribbon of petrolatum mixture to a Finn chamber. The mixture is then applied to the patient’s back.
Conclusions.—This method is a simple way of estimating volume:volume dilutions for skin care products to be patch tested. It is applicable to personal products only; it is not suitable for industrial or household chemicals.
- This relatively simple, 2-page article addresses the issue of dilutions when patch testing with a patient’s skin care products. Many patients are seen with allergic reactions to cosmetics or other products, and it is often beneficial to test directly with these products. Various methods for testing have been recommended, including the repeat open use test, a semi-open test, and occiusive patch testing. Sherertz and Byers offer a simple technique for estimating volume:volume dilutions to provide an appropriate solution for testing.
Evaluation of Previously Patch-tested Patients Referred to a Contact Dermatitis Clinic
Background.—When patch testing does not yield a relevant result that improves patient outcome, clinicians must wonder whether an allergen was missed, whether the screening allergen was relevant, and whether the patient has allergic contact dermatitis. Patients referred to a contact dermatitis clinic who had previous patch testing were studied to find the answers to these questions.
Methods.—The records of 119 patients seen in 1995 were reviewed. Forty-three had had patch testing previously. Nineteen had undergone the True Test, and 24, a screening series presumed to be Hernial. The 43 previously tested were retested.
Findings.—The sites of skin involvement were similar in the previously tested and untested groups. Forty-two percent in the pretested group had been reported to have at least one positive patch test. The most frequently reported allergens were neomycin, quaternium, balsam of Peru, fragrance, and formaldehyde. Seventy-seven percent were positive again on repeat testing. Many findings were thought to be relevant. Nine of the 18 patients had additional allergens considered relevant. Of the 25 patients previously testing negative, 72% had positive allergens on repeat testing, most of which were considered relevant. Seventeen reactions to screening allergens and 16 reactions to additional allergens or products were documented. Variations occurring during initial testing were the use of systemic corticosteroids, patient self-removal of the tests, and single 48-hour readings. Overall, 63% of the pretested patients had relevant additional allergens when tested in a contact dermatitis clinic. Screening allergens were under-recognized as being relevant by clinicians in practice.
Conclusions.—The screening series of allergens should be used in the patch testing of patients suspected of having an allergic component to dermatitis. Interpreting the relevance of the allergens and appropriate avoidance is challenging. When initial screening allergen patch testing is negative or believed irrelevant in a patient with persistent dermatitis, a repeat patch test can have a high yield.
- This study, from a well established contact and occupational dermatitis clinic, is a retrospective chart review of physician-referred patients thought to have allergic contact dermatitis. The authors report the results of patch testing performed on 43 patients who had previously undergone patch testing by a different physician. In their series, Soni and Sherertz confirmed allergies previously diagnosed in the majority of cases and detected positive reactions in 18 of 25 patients who previously had entirely negative results. These reactions were to screening allergens as well as to supplemental allergens or testing with patient-provided products such as cosmetics. The authors conclude that improper technique or lack of regular use of a complete standard screening series of allergens or supplemental allergens may result in a high number of false-negative reactions. Consequently, the diagnosis of allergic contact dermatitis may be missed. The authors acknowledge their bias, in that patients referred to them were felt strongly to have allergic contact dermatitis; however, their results certainly should remind us of the technical difficulties involved with what otherwise seems to be a relatively easy procedure. Referral to a specialty contact dermatitis clinic should be considered when no clear diagnosis can be made in a patient suspected of having contact dermatitis.
Evolution of Contact Dermatitis in Childhood; Cross-Sectional Evaluation of 152 Children
Introduction.—More attention should be given to the evolution of contact dermatitis in children. To assess the history and progression of sensitization in childhood, a study using patch testing was performed.
Methods.—To compare the involvement of specific allergens according to age, 152 children who had skin lesions suggestive of contact dermatitis were enrolled in this cross-sectional analysis and were divided into 4 groups according to age: 3 months to 3 years, 4—7 years, 7-10 years, and 10-18 years. The children had patch tests applied for 48 hours to test for nickel, chromium, cobalt, perfume, balsam of Peru, lanolin, paraben, colophane, and thiuram.
Results.—Patch tests were positive in 104 out of 152 (68%) of children. Nickel sulphate (44% of subjects), bi-chromate (25%), cobalt (21%), and perfume (19%) were the main allergens. There were 35 children who were atopic and of these, 55% were reactive to patch tests. The main allergens were nickel and perfume and children aged 3 months to 7 years were more affected than the older children, with 56% of children 3 months to 3 years, 43% of children aged 4-7 years, and 28% of children aged 7-18 years being affected.
Conclusion.—Rather than allergy, nickel and perfume seem to react through irritation. Irritant dermatitis is likely to be induced by nickel and perfume in infants, whereas older children are likely to have secondary allergic dermatitis from these allergens. Special attention should be given to atopic children, considering their natural skin irritability. They should avoid contact with nickel and perfume.
- This clinical study from France evaluates 152 children, ranging from age 3 months to 18 years, for the incidence of allergic contact dermatitis. Patients, 35% of whom were atopic, were referred with skin lesions suggestive of contact dermatitis. They underwent patch testing, either with selected or with standard allergens. The researchers reported positive results in all groups, with numbers ranging from 73% in younger children to 57% in the oldest group.
When the researchers re-evaluated their results to eliminate “minor reactions,” the incidence of positive reactions fell significantly. They speculate that some of their positive reactions may have been irritant, rather than allergic, in nature. Given the high incidence of positive reactions, this seems to be a reasonable interpretation.
Common positive allergens included nickel, perfume, and chromate. The authors ascribe the nickel and perfume allergies to frequent exposure in childhood, but do not offer any suggestion as to why or how these children could have been exposed to chromates, resulting in positive reactions of up to 35%. Although the number of true positive allergic reactions seems high in this study, it should, nonetheless, remind us that allergic contact dermatitis can, and does, occur in children, and we should not hesitate to perform patch testing when appropriate.
Patch Testing in Children and Adolescents: Five Years’ Experience and Follow-up
Introduction.—Allergic contact dermatitis is now recognized as an important clinical problem in children. However, there are few data on the value of patch testing or the outcomes of children with this problem. A 5-year review of allergic contact dermatitis in children is presented.
Methods.—Patch testing was performed in 83 children with suspected contact dermatitis. There were 47 girls and 36 boys, mean age 12 years and mean duration of dermatitis 5 years. All tests were performed using the European standard series, along with selected preservatives, vehicles, and medicaments. Follow-up data were available on 68 patients.
Results.—A history of reactions to metals was noted in 19 patients, with 10 reacting to nickel, 3 to palladium, 2 to cobalt, and 1 each to chromium and gold. Forty-nine percent of the children had at least 1 allergic reaction. Of the total 84 allergic reactions, 33 were to metals; 22 were to medicaments, topical antibiotics, or cosmetic constituents; 11 were to food additives or flavorings; 5 were to shoe chemicals; 4 were to hairdressing chemicals; and 9 were to miscellaneous allergens.
Patch testing was positive in 7 of 14 patients with oral or perioral symptoms. Relevant reactions in this group included topical preparations, food constituents, isoeugenol, and lip salve. Seven of 29 children had positive allergic reactions, mainly to topical antibiotics and their constituents. Six of 15 patients with foot dermatitis had allergic reactions, including reactions to rubber accelerators. Six of 10 patients with hand dermatitis had relevant reactions. At follow-up, the dermatitis had cleared or improved in 32 of 36 patients with a clinically relevant allergy, but in only 18 of 32 patients with no relevant allergy.
Conclusions.—For children with suspected allergic contact dermatitis, patch testing provides useful information. The ability to identify and avoid an allergen may improve the prognosis. Many of these patients have nickel allergy, which may be related to ear piercing.
- Shah et al. report the results of patch testing in 83 children seen in a contact dermatitis clinic during a 5-year period. The children in this study ranged from 6 to 16 years and had a variety of clinical problems including atopic dermatitis, hand dermatitis, foot dermatitis, perioral dermatitis and other? reactions thought to be possibly allergic. The children were patch tested with standard allergens, as well as supplemental allergens as deemed appropriate. In this group, allergic reactions were detected in 49%; many of these reactions were thought to be relevant to the dermatitis. Common allergens causing reactions included metals, topical medications, food additives, shoe chemicals, and other chemicals. For a majority of those children considered to have a relevant reaction, avoidance led to clinical improvement at 6 month follow-up. This study, like those from other contact dermatitis clinics, may be expected to show a relatively high percentage of positive reactions, reflecting the bias of a referral clinic. The yield in an average practitioner’s office may be lower. Nevertheless, this should dispel the myth that children do not suffer from allergic contact dermatitis and should serve as encouragement to test children when allergic contact dermatitis is clinically suspected.
Patch Test Results in Schoolchildren: Results From the Information Network of Departments of Dermatolgy (IVDK) and the German Contact Dermatitis Research Group (DKG)
Objective.—Contact allergy can play a role in the development of dermatitis and eczema in children. Information on the most frequently en-countered allergens is needed to create an optimal patch test series and to plan approaches to the prevention of allergic contact dermatitis. The results of patch testing in school-age children and adolescents are reported.
Methods.—The retrospective study included the results of patch tests performed in children aged 6-15 years at 22 research centers. Though test chambers were attached for 1 or 2 days, only day 3 readings were included in the current study. The analysis included 416 children, 260 girls and 156 boys. Fifty-four percent of the children were between 6 and 13 years old, and 46% were 14 or 15 years old.
Results.—The final diagnosis was atopic dermatitis in one fourth of children, allergic contact in one fourth, and other diagnoses in one half. Sixty-four percent of girls and 37% of boys had at least 1 positive reaction. Nickel sulfate was the most common allergen, with a reaction rate of 16%; followed by thimerosal, 11%; and fragrance mix, 8%. Nickel allergy was particularly frequent in older girls. Many children had double sensitizations with cobalt salts, potassium dichromate, and palladium. Mercury sensitivity was more common in older children than in younger children. Fragrance allergens were significant sensitizers in both age groups.
Conclusions.—The common contact allergens in children vary by age and sex. The findings indicate the need for improvement in prophylaxis against nickel, mercury, and fragrance allergies. Children can undergo the same patch test methods as adults, though a shortened standard series— including nickel, cobalt, dichromate, thimerosal, fragrance allergens, wool wax alcohols, and Kathon CG—seems appropriate.
- This retrospective study reports the cumulative results of patch testing of children aged 6-15; the data were compiled from 22 different centers of the German Contact Dermatitis Research Group. Four hundred and sixteen children were evaluated; approximately 25% were thought to have contact dermatitis, 50% had allergic contact dermatitis within their differential diagnosis, and the remainder were tested for different reasons. The exact nature of the dermatitis, including areas involved, was not detailed in this study. Of the 416 children, 170 had at least 1 positive reaction. Of interest, the percentage was much higher in girls (63.5%) than in boys (36.5%). Allergens which were frequently positive included nickel sulfate, thimerosal and fragrance mix. There are several problems with this study which make its relevance somewhat difficult to interpret. First, depending upon the test center, the allergens were removed after 1 or 2 days. Most centers now recommend leaving the allergens in place for a full 2 days, so interpretation of these data is not clear. Also, the German study does not comment upon the relevance of the patch test results to the dermatitis, nor does it provide any follow-up regarding clinical outcome after testing. Nonetheless, this study, like others this year, should fully convince us of the usefulness of patch testing children who have what clinically may be an allergic contact dermatitis.
Patch Testing in Discoid Eczema
Background.—Discoid or nummular eczema is characterized by circular or oval plaques of eczema with a clearly defined border. Though a number of factors have been suggested as causative agents, there have been no studies of the relevance of contact allergy in discoid eczema.
Methods and Findings.—Forty-eight patients with persistent or severe discoid eczema underwent patch testing. Mean patient age was 45. The median duration of symptoms was 6 months. Half the patients had positive test results. Of these, 33% were considered clinically relevant. The allergens most commonly found were rubber chemicals, formaldehyde, neomycin, chrome, and nickel. Thirteen of 16 patients were followed up by a phone survey. Sixty-one percent of these patients said that patch testing was beneficial.
Conclusions.—Allergic contact dermatitis appears to be relatively common in patients with persistent discoid eczema. Allergen avoidance may be useful. Patch testing should be considered in all patients with severe or persistent discoid eczema.
- In this retrospective study from the United Kingdom, patients with severe or recalcitrant discoid eczema underwent patch testing. Forty-eight patients were tested; clinically relevant positive allergies were detected in one third. The main allergens implicated by patch testing were rubber chemicals, formaldehyde and formaldehyde releasers, and metals. The investigators feel that patch testing should be done routinely for aft patients with severe or persistent discoid or nummular eczema. This study, like others from a referral-based clinic, suffers from bias in that most patients with nummular eczema are successfully treated and never referred. Consequently, their incidence of positive allergic reactions may be higher than that expected in a general population. However, this should perhaps prompt us all to consider patch testing in any patients with “classic” nummular or discoid eczema who do not respond to conservative therapy.
Contact Hypersensitivity in Patients With Orofacial Granulomatosis
Objective.—Patients with orofacial granulomatosis (OFG) have chronic orofacial swelling related to the histologic finding of noncaseating granulomatous inflammation. The cause of OFG is not known; however, one possibility is contact sensitivity to dietary components. Patients with OFG were tested for contact sensitivity to food additives. In addition, the role of elimination diets in the management of OFG was assessed.
Methods.—Forty-eight consecutive patients with clinical evidence of OFG were studied. There were 26 females and 22 males, median age 24. In addition to individual investigation, the patients underwent patch testing with the European Standard series and an Oral Battery for common food additives. Patients were also assessed for immediate contact reactions to items in the Oral Battery. If clinically relevant reactions were identified on patch testing, the patient was referred to a dietician for a specific elimination diet.
Results.—Forty-two percent of patients had at least 1 positive response to standard patch testing. On patch testing to the Oral Battery, there were 14 positive responses in 10 patients. These 10 patients were placed on elimination diets based on reactions to such constituents as benzoic acid, sodium metabisulfite, and cinnaminaldehyde. Seven patients had definite subjective and objective improvement on their elimination diet.
Conclusions.—Orofacial granulomatosis is a heterogeneous clinical entity that probably has many pathogenetic factors. Patch testing can be useful in the management of patients with OFG by identifying those likely to benefit from dietary manipulation. It may also enhance the ability to target elimination diets appropriately.
- Orofacial granulomatosis is a heterogeneous clinical entity encompassing conditions including Melkersson-Rosenthal syndrome and Miescher’s chronic granulomatouscheilitis. For most of these conditions, the etiology remains unknown. In this study, Armstrong et al. performed patch testing in 48 patients with OFG in whom Crohn’s disease and sarcoidosis had been ruled out. Positive responses were found in 42% of patients, many of which were thought to be possibly relevant, particularly the reactions in 10 patients who were allergic to components of the Oral Battery. Seven patients improved when placed on a diet that avoided exposure to their known allergens. While the results of this study are unlikely to account for all patients with OFG, it should entice us to include patch testing in our diagnostic workup. Again, we see that contact dermatitis is not always a simple clinical problem.
Contact Sensitivity in Pruritus Vulvae: Patch Test Results and Clinical Outcome
Background.—Persistent vulval pruritus is a common disorder. Affected patients may not have signs of a primary vulval dermatosis. In such patients, allergic contact sensitivity is important. The prevalence of allergic contact sensitivity in patients with pruritus vulvae was determined in a retrospective study.
Methods.—One hundred twenty-one women with vulval problems underwent patch testing during a 5-year period. The European Standard Series, selected preservatives, perfumes, local anesthetics, medicaments, and a vulval battery were used.
Findings.—Forty-nine percent of the women had at least 1 relevant allergic positive reaction. The most common allergens to cause reactions were medicaments or their constituents. Of 16 patients with lichen scle- rosus, 7 (44%) had positive reactions. Overall, 55.4% of-the women had significant improvement in or resolution of their symptoms after with-drawal of allergenic substances. Six of the 7 women with lichen sclerosus and positive reactions improved symptomatically. Patients with a relevant allergy were much more likely to improve than those with negative test results.
Conclusions.—The risk of contact sensitivity is high in women with pruritus vulvae and lichen sclerosus. Patch testing provides useful infor-mation for treating such patients, many of whom improve with allergen avoidance.
- In this retrospective study the authors report the results of patch testing in 121 women with vulvar complaints referred to a contact dermatitis clinic. The majority of women suffered from vulvar pruritus, while others had another primary diagnosis including lichen sclerosus, vulvodynia, or vulval vestibulitis. Patients were tested with the European Standard Series, selective preservatives, medications, and perfumes. In this series, positive allergic reactions were detected in more than half the patients, most of which were felt to be relevant to their complaints. Frequent reactions included medications, fragrances, topical anesthetics, and paraphenylene diamine. Perhaps of greater significance, more than 50% of the patients had complete resolution or significant improvement of their symptoms when they successfully avoided products to which an allergy had been detected. This study is clearly limited by its retrospective nature and exhibits the bias one might expect of a specialty clinic; in the “real world,” such a high incidence of positive reactions might not be expected. In addition, it remains unclear in this population of patients whether the contact allergy was the initial cause of itching or resulted from treatment of the pruritus itself. However, this study should remind us that contact allergy can, indeed, be a cause of vulvar pruritus, even when there is no clinical evidence of active dermatitis. Patch testing should be included early in the diagnostic workup in this group of patients.
Is It Really Fragrance-Free?
Purpose.—There are many hidden sources of fragrance that can cause cosmetic contact dermatitis. There is a growing trend toward the use of fragrance ingredients in products labeled “fragrance-free.” These products may be specifically sought out by patients with fragrance allergy. A patient with multiple fragrance allergies who reacted to a “fragrance-free” soap product is reported.
Case.—Woman, 71, was advised to use fragrance-free soap as part of her treatment for contact dermatitis. When her condition did not improve, she underwent patch testing, including a fragrance series. She reacted to a number of different fragrance chemicals, including balsam of Peru, fragrance mix, and rose oil. She also had a questionable reaction to ethylenediamine. Rose oil was identified in the fragrance-free soap the patient was using. Fragrance was also found in an over-the-counter tar soak that had been recommended to her. Her reaction to ethylenediamine was possibly relevant because of her use of hydroxyzine, an ethylenediamine derived antihistamine. The offending treatments were discontinued, and other precautions were recommended, including minimal direct handling of spices and a low-balsam diet. Though the patient’s dermatitis improved, it did not resolve completely.
Conclusions.—Many “fragrance-free” products used by fragrance-sensitive patients may in fact include fragrance. Such patients should be taught to read labels in search of plant extracts that are potential perfume sensitizers and cross-reactors. Rose oil may be a more common allergen than previously thought, perhaps because of its use in products labeled “fragrance-free” or “all-natural.” Manufacturers should label their products more accurately.
- Is it or isn’t it fragrance-free? This question arises frequently among those of us who diagnose and treat allergic contact dermatitis. Unfortunately, as the incidence of fragrance allergy has grown, the need for identifying the presence of fragrances in products has become more important. Dr. Scheinman describes her experience with one woman using a “fragrance- free soap” which was found to contain rose oil. Rose oil is not, at present, contained within the standard fragrance mix used in patch testing. Dr. Scheinman discusses components of the fragrance mix, as well as other possible fragrances which may cause allergic contact dermatitis. Clearly, the cosmetic industry needs to clarify the term “fragrance-free.” We also need to teach our patients, as well as ourselves, to read labels and read them again.
Wrist Dermatitis: Contact Allergy to Neoprene in a Keyboard Wrist Rest
Introduction.—Increasingly used in industry and product manufacture, neoprene seems likely to become a common cause of contact allergy. It is used in rubber gloves, wet suits, face masks and goggles, and computer mouse pads and wrist rests. Neoprene contains the same allergens as those used in rubber manufacturing. A case of contact allergy to neoprene in a computer wrist rest in a patient with known rubber sensitivity is reported.
Case.—Woman, 43, developed vesicles on the palmar surface of her distal wrist over a 48-hour period. Over the next 5 days, eczematous patches developed on her arms, legs, and face. A diagnosis of poison ivy was made, and the patient was put on a 5-day regimen of prednisone. Though her condition improved, the lesions soon recurred in the same areas. On dermatologic evaluation, a long history of rubber allergy was noted. One week before her new problem developed, the patient had bought a mouse pad and wrist rest. Product labeling confirmed that these products contained neoprene. The patient was treated with a 3-week tapering dose of prednisone, with instructions to avoid neoprene and other rubber products. The dermatitis cleared, and remained clear at 1 and 3 months’ follow-up.
Discussion.—Neoprene is a unique compound that is widely used in many different products and industries. More cases of neoprene contact allergy will be seen in the future. Neoprene sources of particular concern include athletic shoes and medical gloves, in addition to computer products.
- This brief case study and review of the literature reports allergic contact dermatitis to neoprene in a keyboard wrist rest. It includes a nice discussion of chemicals used during the production of neoprene, a synthetic rubber used in a wide variety of products including shoes, orthopedic devices, and wet suits. Neoprene is also being used more frequently in the production of some brands of nonlatex surgical gloves. As described in the article, neoprene is modified during production and can include a variety of chemicals, such as thiurams and thiourea compounds. This is important, as most standard series (e.g., the T.R.U.E. Test) do not include thioureas, and failure to test with this allergen may allow thiourea sensitivity to go undiagnosed. We should expect to see this reaction more frequently in the future as the use of neoprene increases.
Allergic Contact Dermatitis From Hydrocolloid Dressings
Introduction.—Hydrocolloid dressings have long been used for the treatment of cutaneous ulcers. There have been few reports of such dressings causing allergic contact dermatitis. The new product DuoDERM E (DuoDERM CGF) contains a sensitizing derivative of colophony. Three cases of allergic contact dermatitis related to the use of this product are reported.
Patients.—All patients had eczematous lesions develop under a DuoDERM E wound covering. Patch testing was performed to the European standard series, to a glues and adhesives series, and to various adhesive dressings. All 3 patients had positive patch tests to colophony, as well as to DuoDERM E or DuoDERM CGF dressings.
Discussion.—The newer hydrocolloid dressings known as DuoDERM CGF, DuoDERM E, Granuflex E, Varihesive E, or DuoDERM Extra Thin consist of an outer occlusive polyurethane layer and a gelatinous, tacky inner core that melts over the wound to create a moist environment. These dressings are very well suited for use on heavily exuding ulcers. Like standard DuoDERM, the newer products contain the synthetic elastomer Vistanex. They also include the pentaerythritol ester of hydrogenated rosin as a tackifier. As a colophony derivative, this substance is potentially sensitizing. Patients sensitized to DuoDERM E or one of the other new products should be able to tolerate standard DuoDERM.
- The use of hydrocolloid dressings has become standard in many dermatology practices. This series of case reports describes allergic contact dermatitis resulting from the use of Duoderm E or Duoderm CGF dressings. Duoderm CGF is a newer version of Duoderm which was apparently reformulated as a controlled gel formulation adapted for the management of heavily exudative wounds. The reformulation of Duoderm to the CGF version resulted in the addition of several new chemicals, including Pentalyn, a pentaerythritol ester of hydrogenated rosin. The 3 patients in this series all reacted to colophony. Two had no reaction to the original Duoderm. This brief series should remind us that products do change as they are reformulated and we must always “read the label.” Likewise, uncomplicated use of a product in the past does not preclude problems in the future.
Contact Dermatitis From Fatty Alcohols
Background.—Mixtures of long-chain aliphatic alcohols are often used as emollients in pharmaceutical and cosmetic formulations. The most common products include lauryl, myristyl, oleyl, cetyl, and stearyl alcohols. The frequency of sensitization to fatty alcohols was examined in a group of patients with suspected cosmetic or medication contact dermatitis.
Study Design.—From May 1992 to September 1995,146 patients, aged 13-72 years, were patch tested with 5 high-grade fatty alcohols: oleyl, myristyl, stearyl, cetyl and lauryl alcohol. These patients had been previously tested with the Italian Research Group on Contact and Environmental Dermatitis standard series and were selected because topical preparations were considered to be a possible source of their contact dermatitis. Patch tests were applied for 2 days using Finn Chambers on Scanpor tape. Readings were made on days 2, 3, and 7.
Results.—Of the 146 patients in the study group, 25 females and 9 males had a positive patch test to fatty alcohols, with 33 reacting to oleyl alcohol. Five of the 39 patients reacted to more than 1 fatty alcohol. Of these 39 reactions, 25 were considered to be clinically relevant. The sources of sensitization were cosmetics in 14 participants, hair-care products in 4, and topical medications in 5.
Conclusion.—The results of patch tests with high-grade fatty alcohols, in a large group of patients with contact dermatitis caused by cosmetics or topical medications, showed that sensitization to oleyl alcohol is not unusual in this group.
- Contact dermatitis from topical preparations, including cosmetics, is not infrequently seen, and determining the exact chemicals implicated in production of the allergy is sometimes challenging. In this study, Tosti et al. evaluate the frequency of sensitization to fatty alcohols including cetyl, stearyl, myristyl, oleyl, and lauryl alcohol. These are frequently present in pharmaceutical and cosmetic formulations, where they function primarily as emollients. In this study, the authors identify a high number of reactions to fatty alcohols, especially oleyl alcohol. They believe that a significant percentage of these reactions was clinically relevant. The percentage of positive reactions to fatty alcohols in this population (23.2%) is certainly higher than would be expected from patch testing with other standard allergens and, unfortunately, while the authors state they tested with other preservatives, the results are not reported. The significance of these findings is therefore unclear. A controlled study to rule out irritation would increase the validity of these results.
Airborne Contact Dermatitis From Unexpected Exposure to Rosin (Colophony): Rosin Sources Revealed With Chemical Analyses
Introduction.—Contact dermatitis can be caused by airborne allergens present in the air as gas, droplets, or solid particles. Studies have shown that the causative agents are generally solid particles encountered in an occupational setting. The 3 cases of airborne contact dermatitis reported here were all traced to exposure to rosin in the workplace.
Case Reports.—Patients were 3 women aged 45-55 years. Two were office workers and 1 was employed in a factory. Rosin was released by linoleum floor material in one of the offices and by a rosin-containing floor polish in the other. One of these workers had facial dermatitis and the other experienced relapsing dermatitis on her eyelids. The factory worker, who had dermatitis on the limbs and upper chest, was exposed to dust from paper cartons. Her dermatitis was probably aggravated by contact allergy to rosin components.
Methods and Results.—Patch testing was performed in all 3 cases, using a standard series and with extracts of materials from the patients’ work-places. Chemical analyses of extracts were conducted with the high-per-formance liquid chromatography method. In the standard series, all 3 patients were found to have + + or + + + reactions to rosin. Two patients also had positive reactions to other substances, including nickel sulfate, cobalt chloride, and p-tert-butylformaldehyde resin.
Discussion.—Rosin is a complex material with several allergens. Although airborne allergic contact dermatitis from rosin exposure is known to have occurred in the electronic industry and in factories in which sawdust is produced from pine species, rosin as a cause of dermatitis was unexpected in these cases. Potential sources of rosin should be investigated when patients with contact dermatitis test positive for rosin sensitivity. Patch testing of suspected rosin-sensitive subjects along with a limited number of controls, combined with chemical analysis, is usually sufficient. Identification of sources of exposure can offer a solution to the patients’ skin problems.
- This article from Sweden describes the presence of rosin (colophony) in unexpected sources; here it caused airborne contact dermatitis in 3 patients. Unfortunately, rather sophisticated techniques, including high-performance liquid chromatography, were needed to detect the rosin in suspected sources, including floor polish and powder from a factory floor. These techniques are not likely to be available to most of us, and these diagnoses may not have been made in many cases. Nevertheless, this article does emphasize the importance of persistence in investigating a patient with suspected allergic contact dermatitis. Referral to a specialty center experienced in handling such problems may be appropriate.
Latex Allergy: Epidemiological Study of 1351 Hospital Workers
Introduction.—Allergy to natural rubber latex has been an important occupational concern in recent years, especially for health care workers. The prevalence of latex sensitization was determined, the occupational and nonoccupational factors associated with latex allergy were assessed, and exposure from wearing gloves or exposure to airborne particles was characterized in a large cohort of health care workers.
Methods.—All 2,062 employees of a general hospital in Hamilton, Ontario, Canada who routinely used latex gloves were invited to take part in baseline screening consisting of a questionnaire, latex skin testing, and serum samples. Glove extracts were assayed for antigenic protein, and exposure to airborne latex protein was estimated once during the summer and once during the winter. The skin sensitivity to 3 latex reagents, 3 common inhalants, and 6 foods was assessed by a skin prick test.
Results.—The mean standard deviation latex protein concentrations were 324 (227) pg/g for powdered surgical gloves and 198 (104) pg/g for powdered examination gloves. Of 1,326 employees who underwent testing at baseline, 160 (12.1%) tested positive for latex allergy. Participants who were sensitive to latex were significantly more likely than their nonsensitive cohorts to have atopy and were significantly more likely to have positive skin tests to 1 or more foods. Employees who were sensitive to latex were more likely to have work-related symptoms that included hives, eye symptoms, and a wheezy or whistling chest. Laboratory workers (16.9%) and nurses and physicians (13.3%) had the highest prevalence of latex sensitivity among exposed employees. Glove consumption per health care worker for each hospital department was grouped into tertiles. The prevalence of latex skin positivity was most prominent in the higher tertiles of glove use for sterile surgical gloves but not for examination gloves.
Conclusions.—The prevalence of positive skin prick tests for latex allergy was about 12% in this cohort of health care workers. There were positive associations between latex positivity and atopy, positive skin tests for food allergies, work-related symptoms, and the departmental usage of gloves per health care worker. Participants will be retested in 1 year to determine the incidence of development of latex sensitivity.
- Latex allergy is rapidly becoming recognized as a serious occupational hazard. This article, written by some of the foremost researchers in the field of latex allergy, is a large, cross-sectional study of health care workers in a Canadian hospital. Workers were surveyed for histories of latex allergy and underwent testing that included latex skin prick testing. A prevalence of latex sensitization of 12.1% was identified in this cohort; they will be followed up to determine the incidence of the development of latex allergy in the future. This number is similar to that which has been reported among health care workers in other studies. This is an important article that should serve as a red flag to all of us in the health care industry, as we are all at high risk for having this potentially disabling allergy. The true incidence of latex sensitization among health care workers is uncertain; additional studies such as this one are needed.
A Survey of Starch Particle Counts in the Hospital Environment in Relation to the Use of Powdered Latex Gloves
Introduction.—The increasing use of latex gloves by health-care workers has led to numerous reports of hypersensitivity to latex. One study has suggested that inhalation of latex proteins attached to starch glove powder could be a significant means of sensitization in the healthcare setting. The presence of starch particles in hospital air was examined by sampling the air in 2 hospitals.
Methods.—The sites tested were those in which glove usage was common. Some sites had mechanical ventilation and others did not. Room air was analyzed for starch particle counts in 3 ICUs, 2 operating theaters, 2 scrub rooms, 2 accident and emergency units, and a sterilization and disinfection unit. A psychiatric ward and a laboratory office were sampled as control settings. Powdered gloves were used in all 3 ICUs, 1 of the 2 operating theaters, and 1 of the 2 accident and emergency units. Starch particles were demonstrated by immobilization onto cellulose acetate filters and staining with iodine.
Results.—Counts of starch particles obtained in air in a total of 421 tests ranged from 0 to greater than 110 (maximum countable) for each 30 1 of air sampled (0 to greater than 3,667 particles per m3). On all 5 occasions when maximum counts were recorded, a pair of powdered gloves had been opened. Counts in 2 of the 3 ICUs never fell to 0. Significantly lower counts were found in the laboratory office and psychiatric ward where no gloves were used. The highest count was recorded in an ICU without mechanical ventilation.
Discussion.—Hospital areas in which starch-powdered latex gloves were used all had readily detectable starch particles in the air. Both mechanical ventilation and the use of powder-free gloves reduced starch- particle counts. A complete change to powder-free gloves can block one of the routes for latex sensitization.
- The incidence of serious allergic reactions to latex has increased significantly over the past few years, perhaps as a result of increased latex use with the adoption of universal precautions. Allergic reactions to latex can include delayed-type hypersensitivity reactions and, more seriously, immediate hypersensitivity or anaphylactic reactions. Glove powder has been identified as a potential vector of latex allergens: latex can be absorbed onto glove powder and aerosolized when gloves are used. This study uses a relatively simple method to quantitate aerosolized starch particles in the hospital environment. As might be expected, high counts were detected in areas where powdered latex gloves were frequently used. This article, and others like it, have likely contributed to the recent National Institute for Occupational Safety and Health recommendation that use of powdered latex gloves be avoided entirely.
Characterization and Identification of Latex Allergens by Two-dimensional Electrophoresis and Protein Microsequencing
Background.—The major cause of immunoglobulin E (IgE)-mediated latex hypersensitivity is proteins of natural rubber latex, which are found in various latex products. This hypersensitivity affects mainly health care workers and patients undergoing repeated surgeries, such as those with spina bifida. The complex nature of natural rubber latex makes it difficult to characterize and to identify the proteins reacting with IgE antibodies in patients with latex allergy. Two-dimensional electrophoresis (2-DE) was used to generate a comprehensive database of latex proteins.
Methods.—Two-dimensional electrophoresis was used to separate proteins extracted from fresh natural rubber latex of Hevea brasiliensis. Sera from latex-allergic health care workers were used in immunoblotting studies to analyze latex IgE-reactive proteins. The latex allergens were identified by protein microsequencing and monoclonal antibodies.
Results.—Approximately 200 distinct polypeptides were identified on the latex C-serum 2-DE map. Two main groups of acidic proteins were eluted from the latex particles, one from the 8-14 kd area and the other from the 22-24 kd area of the 2-DE map. C-serum proteins demonstrated major IgE-reactivity in the 56, 45, 30, 20, 14, and less than 6.5 kd areas of the immunoblots. Distinct IgE reactivity was noted for the 8-14 kd particle proteins, but no staining was found with the 22-24 kd proteins. Seven soluble IgE-reactive protein spots were found to represent previously unknown latex allergens, exhibiting high homology with enolase, superoxide dismutase, triosephosphate isomerase, proteasome subunit, and chitinase. Another 9 proteins corresponded to prohevein, hevein, prohevein C-domain, and hevamine, all known latex allergens. The IgE- reactive latex particle proteins identified by monoclonal antibodies were found to represent mainly the allergenic rubber elongation factor.
Conclusions.—Many IgE-binding proteins can be identified by 2-DE followed by immunoblotting and protein microsequencing. This approach produces 2-DE latex maps useful in developing strategies to isolate relevant latex allergens. The newly identified latex allergens are common plant enzymes; thus, they may also behave as cross-reacting proteins in foods.
- The diagnosis of latex allergy has been significantly hindered by our poor understanding of the exact allergens involved. Several latex allergens have been identified; however, it is clear that different allergens may be involved in allergic reactions in different individuals or groups of individuals. Partly because of this, there is no standardized latex allergen available for prick testing in the United States. This study by Posch et al. uses sophisticated techniques consisting of two-dimensional electrophoresis and protein microsequencing to identify potential proteins which may be involved in latex allergy. The use of two-dimensional electrophoresis allows for high resolution of the different proteins in latex and, in this case, demonstrates the complexity of the various latex proteins. By subsequently immunoblotting with sera from health care workers, the investigators in this study were able to identify several previously-undescribed latex allergens which may also be related to crossreactivity, seen with certain fruits and vegetables. Unfortunately, while this study certainly advances our knowledge of latex proteins and potential allergens, it remains unclear to what populations these results can be generalized. Nevertheless, this is an important study which will in all likelihood enhance our understanding of this serious problem.
Systemic Contact Dermatitis to Hydroxyzine
Introduction.—One of the more difficult diagnoses to make in dermatology is systemic contact dermatitis. Many allergy specialists believe this condition is grossly underreported because it requires a high index of suspicion to identify. There have been several reports of allergic contact dermatitis to topic corticosteroids; thus, some medications given to im-prove cutaneous hypersensitivity can actually worsen it. Similarly, under certain circumstances, oral agents used to treat eczematous conditions can worsen the problem. Systemic contact dermatitis is the term used for provocation of a contact allergy by ingestion of a similar oral agent. Oral antihistamines are often prescribed to treat eczematous rash.es, and the most commonly prescribed is hydroxyzine, a piperazine derivative that is structurally based on a dimer of ethylenediamine. A case of systemic contact dermatitis was reported.
Case Report.—Woman, 48, patch tested positive to ethylenediamine. Several poorly demarcated pruritic red, scaly patches had developed on the trunk and extremities about 2 days after the patient took hydroxyzine, 25 mg, by mouth for mild pruritus. She had patch tests applied and she had a positive reaction to ethylene- diamine dihydrochloride and to potassium dichromate. Her eczema recurred on several occasions after oral provocation with hydroxyzine. When the patient discontinued hydroxyzine, her pruritus and skin lesions disappeared.
Results.—Hydroxyzine, a common medication use to treat pruritus, may be a potential cause of unresponsive eczema perpetuated by systemic contact dermatitis. Several topical medications contain ethylenediamine, including piperazine antihistamines, motion sickness medications, menstrual analgesics, nasal sprays, and antipsychotic drugs.
Conclusion.—In the differential diagnosis of any eczematous condition that is resistant to standard treatment, it is important to consider systemic dermatitis. A thorough patient history should be taken, including all topic exposure at work and at home, and a history of any oral medications.
- This brief case report describes a patient with systemic contact dermatitis to hydroxyzine. As this antihistamine and other related antihistamines, including cetrizine, are frequently used by dermatologists, this condition may not be uncommon. Unfortunately, as the authors suggest, it may go unrecognized and the medication used to treat a problem may actually become the problem itself. The authors provide a good review of hydroxyzine and its structural cousin, ethylenediamine. Contact allergy to ethylenediamine can be easily detected using standard patch test batteries. The authors also include a list of medications related to ethylenediamine with which all dermatologists should be familiar (as a means of avoiding this type of problem in the future.
Papular Urticaria: A Histopathologic Study of 30 Patients
Introduction.—Papular urticaria (PU), a common disease of infancy and childhood, is caused by hypersensitivity to bites from insects such as mosquitoes, fleas, and mites. Patients typically exhibit symmetrically dis-tributed pruritic papules and papulovesicles. A prospective study was designed to document the histopathologic features of papular urticaria.
Methods.—Patients were considered to have PU if they exhibited a widespread, symmetrical eruption consisting of reddish papules and/or papulovesicles near readily identifiable insect bites. The median age of the 30 patients who met this definition was 21 months. Punch biopsies were taken for histopathologic and immunofluorescence studies.
Results.—Mild acanthosis and variable spongiosis were present in all biopsy specimens; 41.4% showed marked spongiosis. Other frequent findings included spongiotic acrosyringitis (41.4%) and epidermal exocytosis of lymphocytes (53.3%). Eosinophils and neutrophils were present in all but 4 biopsy specimens; interstitial eosinophils occurred in 58.6% of cases. Sparsely distributed mast cells were present in all cases. Immunohis- tochemistry, performed in 10 patients, revealed abundant T lymphocytes (CD45RO, CD3) and macrophages (CD68) in all cases. Absent were B lymphocytes (CD20) and dendritic antigen-presenting cells (S100). Direct immunofluorescence staining failed to demonstrate deposition of IgA, IgG, IgM, C3, or fibrin.
Discussion.—The frequent presence of eosinophils and mast cells in the skin lesions of patients with PU supports the idea of a type I hypersensitivity reaction in response to an antigen deposited by an arthropod bite in a sensitized patient. Because histopathologic features are not specific, it may be difficult to distinguish PU from papular atopic dermatitis. Diagnosis requires careful clinicopathologic correlation.
- The authors conclude that the histopathologic features of PU are nonspecific and that a diagnosis can only be rendered after careful clinicopathologic correlation. Their data provide morphologic and immunohistochemical evidence that supports a role for a type I hypersensitivity reaction in the pathogenesis of the disease.