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Cutaneous Drug Eruptions
Skin Cancer Prevention
Skin Disease in HIV
Psoriasis and allergic contact dermatitis (ACD) have long been considered to be mutually exclusive conditions.
Methods: During a retrospective analysis of 186 consecutive patients who underwent comprehensive patch testing at the University of Miami from December 2004 to December 2006, we did a subanalysis of the 15 psoriatic patients who had undergone patch testing. All of the psoriatic patients were referred for worsening chronic plaque psoriasis because of suspected ACD. These patients' results were compared with an age- and gender-matched comparison group with chronic dermatitis and no self or family history of autoimmune diseases (including psoriasis).
Results: We found that the 15 psoriatic patients all had clinically relevant allergens identified during patch testing to the North American Contact Dermatitis Group standard screening series and supplemental allergen panels based on history. In the psoriasis group, 75% of the top 12 allergens were found to be associated with personal hygiene regiments or topical treatments. The top 4 allergens in both groups were nickel sulfate, cocamidopropyl betaine, balsam of Peru, and methyldibromoglutaronitrile.
Conclusion: We conclude that patients with psoriasis are capable of having concurrent ACD and their therapeutic products are a frequent source of allergens.
The prevalence of allergic contact dermatitis (ACD) in patients with psoriasis vulgaris is not well established. Furthermore, the literature has conflicting data regarding rates of positive patch tests in psoriatic patients (Clark & Sherertz, 1998; Henseler & Christophers, 1995; Heule, Tahapary, Bello, & van Joost, 1998; Malhotra, Kaur, Saraswat, & Kumar, 2002; Moss, Friedmann, & Shuster, 1981; Pigatto, 2000; Stinco, Frattasio, De Francesco, Bragadin, & Patrone, 1999). During a retrospective review of 186 adult patients patch tested between December 2004 and 2006, we identified a subgroup of 15 patients (8% of the patients tested during that time frame) with chronic, moderate plaque psoriasis who had been referred for evaluation because of worsening psoriasis and suspected ACD. We then analyzed this group to determine the frequencies of allergens and the clinical relevance of these allergens to their worsening disease state.
Fifteen patients with chronic plaque psoriasis (11 female and 4 male; age = 41-85 years, mean = 59 years, median = 60 years) were evaluated against a comparison group of 15 age- and gender-matched patients with worsening chronic dermatitis (11 female and 4 male; age = 41-82 years, mean = 58.5 years, median = 60 years) and no personal or family history of autoimmune diseases (psoriasis, lupus, Crohn's disease, Hashimoto's thyroiditis, or Graves' disease).
All 30 of the patients were referred for evaluation of presumed contact dermatitis and patch tested to the North American Contact Dermatitis Standard Screening series and supplemental allergen trays on the basis of their history and clinical presentation. After the patch test procedure, the patch test physician counseled the patient on how to perform repeat open application testing (provocation testing) to confirm the clinical relevance of the positive patch tests. On follow-up evaluation, the positive patch was deemed of "definite" clinical relevance when the dermatitis corresponded to point(s) of contact with that allergen, the allergen was found to be present in the patient's current environment, and the dermatitis significantly improved upon avoidance of the allergen or recurred when the patient recontacted the allergen (rechallenge). If upon evaluation the allergen met the criteria of definite, but no follow-up information was available, then a "probable" clinical relevance was assigned. When only one criterion was met, the positive reaction was assigned a "possible" relevance. In the event that no clinical relevance could be assigned, the allergen was marked as "unlikely" or past.
The mean number of individual allergens placed on the patients was 115 in the psoriasis group and 120 in the comparison group. In the 15 plaque-type psoriatic patients, there were 56 different clinically relevant allergens identified, whereas the comparison group patients demonstrated 49. There was no significant difference in the median number of positive patch tests per patient, with a median of 5 positives per patient in the psoriasis group and 4 positives per patient in the comparison group. Four allergens were at the top for both groups: nickel sulfate, cocamidopropyl betaine (CAPB), balsam of Peru (BOP), and methyldibromoglutaronitrile (MDGN).
The top 12 clinically relevant allergens for the psoriasis patients are shown in Table 1. Nine of these top 12 allergens (75%) were associated with personal hygiene products (e.g., CAPB, a surfactant, MDGN, preservative, and fragrances), topical medications (e.g., diazolidinyl urea, preservative in medical cream), or treatments (e.g., carbamates and colophony because of exposure from occlusion therapy with gloves and adhesive tape). Metal allergy (nickel, chromate, and cobalt) correlated with hand and foot involvement in 87.5% (7/8) of the patients. Of the 5 nickel allergic patients, 3 (60%) were also found to be allergic to cobalt and 2 (40%) to potassium dichromate. Overall, clinical improvement was noted in 86.6% (13/15) of the psoriatic patients when the offending allergen was removed versus 73.3% (11/15) in the comparison group, resulting in clinically manageable plaque psoriasis, treatable with allergen-free conventional topical medicaments (i.e., corticosteroids, compounded calcipotriol).
Previous research had suggested that psoriasis leads to cutaneous anergy because it is a Th1-dependent condition (Henseler & Christophers, 1995). More recently, however, Myers, Newman, Katz, and Gottlieb (2006) demonstrated the potential for psoriatic patients to develop ACD even while on anti-tumor necrosis factor [alpha] therapeutics. Furthermore, researchers abroad have reported that a statistically significant number of palmoplantar psoriasis patients have been found to have positive patch tests, with a confirmed role of the associated contact allergens in the triggering and/or perpetuating their psoriatic lesions and pustular psoriasis patients' psoriatic condition being aggravated by contact allergens (Caca-Biljanovska, V'lckova-Laskoska, Balabanova-Stefanova, & Grivceva-Panovska, 2005; Jo, Jang, Ko, Kim, Oh, Kwon, & Kwon, 2005; Katugampola, Hughes, Mills, & Stone, 2007). Likewise, our data suggest that psoriasis and ACD are not mutually exclusive. All of the 15 psoriatic patients referred to our center had at least one clinically relevant allergen. The comparison group was chosen to represent a group of patients who were also patch tested during the same time frame while controlling for age, gender, and autoimmune influences. The similarity between the psoriatic and the comparison group allergens suggests that patients with psoriasis should be regarded as having the same response to sensitizing allergens as those chronic dermatitis patients without a comorbid skin condition.
All 186 of the adult patients referred for comprehensive patch testing were suspected of having ACD by their primary referring dermatologist. The 15 psoriasis patients were specifically referred for evaluation of contact dermatitis as a trigger for clinically worsening psoriasis by nine different referring dermatologists.
Subsequent to comprehensive patch testing, all the patients were extensively counseled on the avoidance of their triggering allergens. When possible, patients also underwent provocation testing with their personal products to confirm their allergy.
CAPB was found to be the top clinically relevant allergen. This zwitterionic, coconut-oil-derived surfactant was found in a significant number of personal hygiene products in both groups (i.e. "sensitive skin" body washes, "no tears" shampoos, and soaps; Shaffer, Jaimes, Hordinsky, Zielke, & Warshaw, 2006). Although CAPB is less irritating to mucous membranes than traditional surfactants, it is a potential allergen. The dermatitis tends to present around the eyelids, scalp, and face because of the use of "sensitive skin" formulations in these areas by the patients with chronic skin disorders. CAPB was named Contact Allergen of the Year in 2004 by a committee of international experts because of the rapid emergence of this allergen as a frequent source of ACD (Fowler, 2006).
Nickel was the second most common allergen identified in both groups of patients. This likely reflects the high prevalence of nickel allergy in the population as a whole, with nickel being the most frequent allergen in the United States in most published series (Pratt et al., 2004). The correlation found in our patients between hand and foot dermatitis and nickel allergy is supported by other studies (Lazzarini, Duarte, & Marzagao, 2004; Magina, Barros, Ferreira, & Mesquita-Guimaraes, 2003). Although foot dermatitis may be frequently associated with rubber accelerators, shoe ornaments made of nickel are also a common contact allergen. Nickel is a frequently encountered allergen with exposure via metal snaps on clothes and bags, costume jewelry, food, doorknobs, eyeglass frames, and many other common household items with increased exposure if encountered in the presence of sweat (Jacob & Amado, 2005). Patients with nickel allergy also may have a concurrent chromate and or cobalt ACD because of cosensitization and coreactivity, respectively.
BOP was a frequent allergen in both the psoriatic group and the comparison group. This allergen is a ubiquitous fragrance and flavorant with many constituent chemical components. It is derived from the sap of the Myroxylon balsamum tree. Fragrances and BOP have been reported as the third and fourth most common allergens identified during comprehensive patch testing in the United States by the North American Contact Dermatitis Group (Pratt et al., 2004). Because of the frequent identification of fragrance allergy during patch testing, fragrances were named Contact Allergen of the Year in 2007 (Storr, 2007). BOP and fragrance exposure in our studied set of patients was frequently associated with personal hygiene products and topical therapeutic agents that they used to cleanse and treat their chronic dermatitis. Post-patch test counseling of the patients with hand dermatitis who had demonstrated patch test positivity to BOP included the advice to perform a trial avoidance of eating or handling tomatoes because of their high concentration of cinnamic alcohol (a component of BOP). All patients with a positive patch test to BOP or fragrance were advised to only use "fragrance-free" products, not "unscented" as these products may contain masking scents.
MDGN was also identified in the top four allergens of psoriatic patients during this study. MDGN is a preservative agent often marketed as Euxyl K400. It can be found in topical cosmetics and creams. Of note, it was the 11th most common allergen identified in one large series (Pratt et al., 2004). However, in our subset of psoriatic patients, it was overrepresented.
Of special note, three of our psoriatic patients had clinically relevant positive patch tests to diazolidinyl urea, the formaldehyde releasing preservative in their Dovonex cream(R) (Leo Pharma, Ballerup, Denmark). Only one of these three patients demonstrated a positive reaction to formaldehyde, which underscores the ability of this chemical to be an allergen independent of formaldehyde sensitivity (Rietschel et al., 2007). As has been previously described by others, we confirmed the clinical relevance of this allergen in the therapeutic cream by performing provocation tests (Krayenbuhl & Elsner, 1999). Furthermore, one patient was found to have a clinically relevant Bronopol (another formaldehyde releasing preservative) positive patch test, confirmed by provocation testing with her "Dead Sea" personal hygiene-healing products (Ahava, Ahava NA, LLC, Bristol, RI). This underscores the need for awareness that herbal/natural products may contain preservative based allergens.
This report highlights our preliminary data on clinically relevant patch tests in patients with chronic plaque psoriasis who were referred for worsening psoriatic disease. We realize the limitations of drawing conclusions on the basis of a small data set; however, we believe that the diagnosis of ACD should be considered in patients with worsening plaque psoriasis, as our data suggest that they have similar rates of positive patch tests and allergen profiles to other patients with chronic dermatitis.
Dermatology nurses and nurse practitioners caring for patients whose psoriasis is not responding as expected should consider ACD as a possible confounding diagnosis, especially in those with a history of contact allergies or long-term topical medicaments. Investigating whether a reaction to an allergen in a prescription or other product may be confusing, and even worsening, the clinical picture could lead to an improved outcome for the patient and help explain halting improvement or worsening disease in the past.
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