Systemic Contact Dermatitis Dianne L

Allergen Focus Systemic Contact Dermatitis Dianne L. Silvestri, MD

in time, even to something that the patient has been using regularly for a short period of time or intermit- tently for years. In certain cases, other related disorders such as irritant contact dermatitis (ICD) and contact urticaria (CU) may be relevant; history, rather than patch testing, can point to these as the correct diagnosis for the patient. It is important to note that ICD, the most prevalent form of contact dermatitis, can, at times, precede or occur concomitantly with ACD.4,5 Unlike ACD, ICD is not immune- mediated. It occurs secondary to contact with an irritating or abrasive substance. CU, on the other hand, represents the least prevalent form of ICD. The wheal and flare reaction of CU is an IgE- and mast cell-mediated immune phenomenon of immediate- type hypersensitivity. Although this form of contact reaction is rare, it is important to recognize because of its potential to produce serious anaphy- lactic-type reactions.6–8 This column highlights ACD, focus- ing on significant allergens, regional llergic Con- to comply with allergen avoidance are presentations of dermatitis and top- tact Dermati- at risk for recurrent or sustained der- ic-based allergic manifestations and tis (ACD) is an matitis or progression to a systematized offers clinical tips for diagnosis and A 2,3 important disease that presentation. In fact, patient education treatment. This month, we feature an affects 14.5 million often begins before the diagnostic patch uncommon but especially important Americans each year.1 tests are ever placed, to ensure that ACD category of allergic dermatitis — sys- Dianne L. Slivestri, MD The economic im- patients have an appropriate under- temic contact dermatitis. pact of this condition standing of potential outcomes and the is high, whether mea- central role patients play in both their Systemic Contact Dermatitis sured by patient morbidity, health care disease and treatment. Systemic contact dermatitis (SCD) is expenditures, loss of income or lost time During the initial consultation, an interesting subset of ACD that may from school and work.1 Once patch test- patients are often taught about the occur more often than clinically recog- ing is performed and an allergen source delayed presentation of ACD and its nized. SCD refers to the development has been identified, education becomes relationship with the immune system of dermatitis upon systemic exposure the critical intervention to ensure ad- (sensitization to a chemical and elici- to an allergen in someone previously herence to an avoidance regimen. With tation of a dermatitis with re-expo- sensitized to that chemical through cu- allergen avoidance, remission of the der- sure). Furthermore, they are instruct- taneous contact. Since this process was matitis ensues. Patients who are unable ed that it may develop at any point first recognized, several terms other than

22 January 2012 | Skin & Aging | www.skinandaging.com Allergen Focus

SCD have been suggested to describe Table 1. Alternative Names For Systemic Contact Dermatitis it.9–21 See Table 1. Elicitation of dermatitis by allergen Endogenic contact eczema9 Internal-external contact-type hypersensitivity10 exposure through routes other than trans-cutaneous contact was first de- Contact type dermatitis medicamentosa11 Mercury exanthem12 scribed by Jadassohn in 1895.22 He re- Hematogenous contact eczema13 Baboon syndrome14 ported that individuals topically sensitized to mercury developed dermatitis Systemic contact-type dermatitis15 Paraptic eczema16 after systemic mercury exposure. Dur- ing World War II, Park recognized Systemically induced contact dermatitis17 Systemic reactivation of allergic contact dermatitis19 cutaneous eruptions occurring in pa- 21 tients previously topically sensitized Symmetrical drug-related intertriginous and flexural Systemic allergic dermatitis exanthema20 to sulfonamides when those antibiot- ics were administered orally.23 In 1951, Leifer reported that ingestion of cinnamon oil precipitated a recurrence of Table 2. Diverse Presentations Of Systemic Contact Dermatitis hand eczema in a patient allergic to Reactivation of patch test site Pompholyx (dyshidrotic eczema) cinnamon.24 In 1954, Sidi and Melki demonstrated flares of eczema in chro- Aggravated local allergic contact dermatitis Reactivation of a previously sensitized area mium-sensitive patients given an oral (recall reaction) challenge of potassium dichromate.25 Disseminated patchy dermatitis Generalized erythroderma Three years later, Pirila described both reactivation of a thiuram patch test Baboon syndrome (SDRIFE) Vulvar pruritus or dermatitis and widespread dermatitis appearing in a patient given oral antabuse (tet- Pruritus ani Cheilitis 25 raethylthiuram disulphide). In 1958, Lichen planus of the lip Hjorth reported a girl sensitized to thiamine through occupational contact who developed dermatitis after revealed sensitivity to dust mites. En- Pathophysiology Of ingesting the vitamin.26 Similarly, after vironmental modifications were un- Allergic Contact Dermatitis handling streptomycin while treating dertaken to reduce dust mite exposure, The immunologic basis for SCD is tuberculosis patients, nurses subse- but symptoms persisted. She was then not completely understood and may not quently erupted with dermatitis when instructed to avoid common contact be identical for all allergens. As reviewed they received injections of the antibi- allergens, including formaldehyde re- recently by Jacob and Zapolanski,28 dur- otic.27 Describing another instance of leasers and fabric resins, but she resist- ing allergen sensitization, a hapten pen- medication-induced SCD, Pirila de- ed eliminating her favorite perfumes. etrates the skin and reacts with resident tailed in 1960 the development of a Biopsy showed perivascular lympho- antigen-presenting dendritic cells that widespread dermatitis from neomycin cytic infiltrate with prominent eo- transfer the bound antigen to T lym- inadvertently administered orally to a sinophils. Patch tests were performed phocytes. Once these cells are primed patient with previous contact sensiti- with a modified panel of 65 allergens and reproduce, they return to the skin, zation.9 Over the decades since these and read at 48 and 96 hours. Positives ready to act on target cells when the an- early reports, the scope of allergens has were found for propylene glycol, dis- tigen is encountered again. It seems that broadened and the reported routes of perse blue dyes 106 and 124, cocami- the immune system can be activated by exposure have multiplied. dopropyl betaine, oleamidopropyl di- allergen exposure as well through oral methylamine and vanillin. The patient and other systemic routes, triggering the Case Report changed her brand of acetaminophen activated CD8+ effector T cells.29 A 13-year-old Asian female was re- after discovering propylene glycol ferred for a fingerprint-like dermatitis among its ingredients. She was no Diverse Presentations of covering her chest, abdomen and back longer wearing dance leotards, which Systemic Contact Dermatitis present for 2 years. Her prominent may have been a source of previous Systemic provocation by allergen in nocturnal pruritus was only partially exposure to azo dye. She continued the allergic patient can produce many relieved by topical steroids. On exam, use of her desoximetasone ointment different types of dermatitis. See Table she had dozens of post-inflammatory and substitute shampoo, both free of 2. Reports often describe a reactivation hyperpigmented oval macules, as well her allergens. At follow-up visit, the or exacerbation at the original cutane- as slightly scaly small plaques, pink in patient reported that her symptoms ous location or acceleration to a more color and thin, covering her trunk but and rash improved when she began to widespread dermatitis, occasionally a sparing her face, neck and extremities. avoid her nightly vanilla ice cream; she generalized erythroderma. Frequently, Epicutaneous testing by the allergist flared if she resumed eating it. systemic exposure to a demonstrated

January 2012 | Skin & Aging | www.skinandaging.com 23 Allergen Focus allergen incites reactivation of the rel- es.54 Veien also demonstrated provo- published since Hjorth first described evant patch test site.30,31 Recall of prior cation of dermatitis by an oral dose an association between balsam of Peru localized dermatitis has been described of balsam of Peru.55 He studied this patch test reactivity and sensitivity to by Giordano-Labadie and colleagues relationship further by demonstrating aromatic spices and flavorings.54 Bal- when perianal dermatitis, previously flares of eczema after oral challenge sam of Peru, a fragrant extract from the produced by a cream that contained with graduated doses of nickel, co- Latin American Myroxilon pereirae tree, is sorbic acid, was provoked in a patient balt, chromium and balsam of Peru in a composite of many sensitizing chem- by ingestion of sorbic acid-containing patch-test positive patients.56 He pro- icals. It is used as an allergen in patch foods, such as strawberries, candies, posed depletion diets to benefit indi- testing to detect fragrance sensitivity. margarine and cheeses.32 Fisher de- viduals with positive patch tests to or Veien and colleagues have demonstrated scribed a woman who, after previously history of aggravation by ingestion of dermatitis flares in patients orally chal- reacting to propylene glycol in vaginal these allergens. Jensen and colleagues lenged with the substance.55 Ingestion lubricant jelly, later developed vulvar were able to show a dose-dependent of its component flavorings, including pruritus upon receiving intravenous relationship between ingested nickel cinnamon, cloves and vanilla, has also diazepam containing propylene gly- and flare of dermatitis.38 Based on a been reported to instigate widespread col.33 Other authors have also reported subsequent meta-analysis, they con- SCD.65 Observance of dietary restric- pruritus ani34,35 and vulvar dermati- cluded that normal daily consumption of balsam of Peru components tis34,36,37 as manifestations of SCD. tion of nickel is sufficient to ag- may benefit many sensitive patients, The most widely studied and repro- gravate dermatitis in some sensitive including children.3,45,52,66 In our clinic ducible manifestation of SCD is pom- individuals.57 A low-nickel diet im- we recently evaluated a balsam of Peru pholyx, deep-seated vesicles of the palms proved dermatitis after just 4 weeks patch-test positive woman whose hand and lateral fingers and, in some cases, in nearly two-thirds of 90 patients and patchy dermatitis developed when feet. This so-called “dyshidrotic eczema” studied by Veien and colleagues, and she began to consume six or more cans can be precipitated by oral administra- after more than one year, 73% of of Dr. Pepper daily at her new job and tion of nickel, cobalt and chromium.38–43 respondents continuing the diet re- subsided when she weaned herself from It may erupt after ingestion of spices44 ported improvement.58 Exacerbations this spicy beverage. and can improve with reduction of di- of dermatitis in nickel-sensitive in- More rarely reported are incidents etary components of balsam of Peru.3,45 dividuals may occur after seemingly of SCD related to ingestion of preser- Perhaps the most unique presenta- benign intake of cocoa59 and herbal vatives and excipients. Although many tion of SCD is the so-called baboon vitamin or mineral supplements.60 patients have contact sensitization to syndrome, with its demarcated ery- Veien and colleagues also reported formaldehyde and formaldehyde releas- thema of the buttocks, axillae and up- flare of dermatitis in cobalt-sensitive in- ers, food sources of formaldehyde are per inner thighs.14 Many of these cases dividuals after oral dosing with 1 mg co- limited. Recent reports affirm that the have been reported from exposure to balt sulfate.39 Response to oral challenge artificial sweetener aspartame, which is mercury inhaled from broken ther- in those patch-test positive to cobalt but metabolized in the body to formalde- mometers or ingested in homeopathic not to nickel was useful for predicting hyde, may induce SCD when ingested preparations after presumed sensiti- which patients would subsequently ben- by formaldehyde-sensitive individu- zation through topical application of efit from a diet low in cobalt.40 Stuckert als.53,67 Aspartame is not only commer- mercurochrome.46–48 Because this pe- and Nedorost have recently updated di- cially available as a sugar substitute, but culiar pattern is most often described etary cobalt guidelines by proposing an it is an ingredient in innumerable foods, as a drug reaction, rather than a conse- easy-to-use point system.41 beverages and chewable or syrup forms quence of systemic exposure to a prior Oral ingestion of metals may be es- of medications. contact allergen, some authors have pecially likely to aggravate the pom- The parabens, para-hydroxybenzoate proposed distinguishing symmetric pholyx pattern of hand dermatitis. This preservatives, have been widely utilized drug-related intertriginous and flex- was suggested in a double-blind trial of for decades, but they are currently em- ural exanthema (SDRIFE)20,49 from the potassium dichromate versus placebo ployed in personal products in much baboon presentation of SCD. by Kaaber and Veien,61 as well as a later lower concentrations than in the past.68 Less common presentations of SCD placebo-controlled study dosing chro- Veien and colleagues were able to pre- include cheilitis,50 lichen planus of the mate-positive patch test patients orally.62 cipitate cutaneous flares in only a few lip and oral mucosa,51 perioral dermati- In addition to normally occurring di- of their 14 sensitive patients challenged tis52 and eyelid dermatitis.53 etary chromium (eg, in black pepper, orally,69 but generalized dermatitis has apple peel and brewer’s yeast), the metal been reported in sensitized individuals Allergens Ingested Orally introduced through multivitamin and following ingestion of paraben-con- A large number of allergens have mineral supplements63 or the nutritional taining medicaments, including halo- now been described that produce additive chromium picolinate may cause peridol70 and a mucolytic.71 Paraben- dermatitis after oral ingestion. Hjorth patients to flare.64 sensitive individuals seldom experience was among the first to describe der- Numerous reports of dermatitis exac- flare of dermatitis from consuming matitis induced by administered spic- erbated by ingestion of spices have been paraben-containing foods such as pro-

24 January 2012 | Skin & Aging | www.skinandaging.com Allergen Focus cessed tomato products, pickles, relishes Table 3. Reported Routes of Systemic Exposure to Contact Allergens and packaged meat products.68 Propylene glycol is a widely used hu- Oral Intravenous mectant and solvent for foods as well as Subconjunctival Intraarticular topical and systemic medicaments. Han- nuksela and Forstrom demonstrated that Intramuscular Subcutaneous oral propylene glycol caused eczema in Pulmonary inhalation Intradermal some patients shown to have contact allergy to the chemical.72 More recently, Intranasal Dental Lowther and colleagues73 described Intrauterine Intratubal a woman whose dermatitis improved Endocardial Endovascular with avoidance of numerous topical preparations that contained propylene Arthroplastic glycol, to which her patch test showed questionable reactivity. Her dermatitis spread eczematous patches perpetuated Intramuscular injection of gold was recurred, however, at previous locations by chronic oral and topical aloe use.80 a common treatment for rheumatoid and at the patch test site when she ate arthritis in the past. In patients with foods known to contain propylene gly- Other Routes of Allergen Re-exposure contact allergy to gold, such injections col, such as sauces, dressings and snack Ingestion by mouth is just one of the can provoke severe skin reactions.90 Al- foods. We have seen a propylene glycol many recorded routes of systemic expo- though allergic reactions to subcutane- patch test positive boy whose dermatitis sure to cutaneously sensitized allergens. ously injected insulin are only rarely due cleared when his topical corticosteroid See Table 3. Intravenous administra- to the metacresol preservative and most was changed to a propylene glycol-free tion of propylene glycol precipitated of those reactions are local, one case of alternative, but then flared each spring the related vulvar recall reaction men- exfoliative erythroderma has been cred- when, for respiratory allergies, he re- tioned above.33 Aminophylline, a com- ited to SCD from this agent.91 sumed his oral antihistamine pill con- pound of theophylline and ethylenedi- Pulmonary inhalation of the cor- taining propylene glycol. amine, whether given intravenously or ticosteroid budesonide has been re- Plants in the large Compositae (As- orally, has produced baboon syndrome ported to reactivate previously positive teraceae) family are common sensitizers and generalized exfoliative dermatitis in budesonide patch tests, provoke new through repeated contact. Recently, de- patients previously sensitized to ethyl- distant skin lesions and display cross- rivatives of many species, such as fever- enediamine by topical application of a sensitivity to other group B cortico- few, calendula and Arnica montana, are product containing it.81–83 Because this steroids such as triamcinolone aceton- being formulated into topical personal amine is the parent compound of the ide.31 Other groups of corticosteroids products. Dietary sources are even more hydroxyzine family of antihistamines, and other routes of administration, such plentiful and reports have been pub- these drugs should also be avoided in as oral, intravenous, intraarticular, intra- lished of flares of Compositae-acquired sensitive patients. dermal and intranasal, have also been dermatitis after eating lettuce, chicory Neomycin is a common contact aller- associated with SCD.92–94 A study by and endive,74,75 consuming chamomile gen, with ubiquitous exposure in over- Mahajan and colleagues demonstrated tea75,76 and ingesting Echinacea.77 the-counter antiseptic preparations. Ex- SCD caused by inhalation of plant ma- Propolis, also known as beeswax or posure to the antibiotic orally can trigger terial from the allergenic weed Parthe- bee glue, is a hive cement and protec- a flare at former sites of contact der- nium.95 Inhalation is also one route by tant generated by bees using substances matitis or a widespread dermatitis.13,84 which mercury has caused SCD,12,47 collected from poplar resin and conifer Gentamicin, tobramycin and framycetin although allergen exposure may also buds. It is a potent sensitizer, as well as a are very closely related to neomycin come from ophthalmologic prepara- potential cross-reactor with both Com- structurally and they have produced re- tions and dental amalgams.96 positae and balsam of Peru. Not only is actions as severe as erythroderma when Whereas reactions to dental amalgam it found widely in cosmetics, lip balms, administered to neomycin-sensitive metals such as mercury, gold, nickel, pal- toothpastes, chewing gums and a host patients either intravenously,85 subcon- ladium, copper, cobalt and chromate of other products, but it is also present junctivally86 or intra-articularly in bone usually present as localized adjacent in some coated oral pills, cough syrups cement.87 Although erythromycin is buccal lichenoid sores97 and less com- and gummy vitamins. Consumption of seldom a topical sensitizer, one patient monly as SCD, nickel in dental braces these can elicit SCD.78 Royal jelly and is described in whom contact rash was has been reported to produce not only propolis-comprised “alternative” prod- followed by a generalized eczema after mucosal reactions, but also significant ucts for “immune enhancement” may the antibiotic was prescribed orally.88 cutaneous dermatitis requiring appli- precipitate generalized rashes in sensi- Various reactions have been reported to ance removal.98–100 tized individuals.79 Decades ago, Mor- acyclovir given orally or intravenously Allergic dermatitis, although rarely row and colleagues reported a similar in patients previously sensitized through reported from a copper intrauterine aloe-positive patch test man with wide- topical application of the ointment.89 device, has been documented by posi-

January 2012 | Skin & Aging | www.skinandaging.com 25 Allergen Focus tive patch test to copper sulfate and re- days or years may pass before an allergic University of Massachusetts Medical Center versal after removal of the IUD.101–105 dermatitis erupts.115 Exposures may be in Worcester, MA. Recently, a woman without prior rec- additive, eventually causing the immune ognized allergy developed generalized system to cross a metaphorical “thresh- References pruritus and nausea following insertion old,” after which subsequent contact 1. Bickers DR, Lim HW, Margolis D, et al. The of an intratubal birth control device elicits a cutaneous response.4 Just as re- burden of skin diseases: 2004 a joint project of the American Academy of Dermatology Association and composed of a stainless steel coil cov- peated contact over time leads to the the Society for Investigative Dermatology. J Am Acad ered by the nickel-titanium alloy niti- immune allergic response, persistent Dermatol. 2006;55(3):490-500. nol. Patch tests were positive to nickel avoidance of exposure over time may be 2. Hsu JW, Matiz C, Jacob SE. Nickel allergy: local- and nitinol and the patient had im- required to induce remission. Patients ized, id, and systemic manifestations in children. Pedi- atr Dermatol. 2011;28(3):276-280. provement of symptoms after prompt must be enlisted to become actively 3.Salam TN, Fowler JF. Balsam-related systemic contact 106 removal of the implant. involved in the management of their dermatitis. J Am Acad Dermatol. 2001;45(3):377-381. In addition, nitinol composes the only dermatitis. It is helpful to provide them 4. Nijhawan RI, Matiz C, Jacob SE. Contact der- presently approved device for percutane- clear written instructions accompanied matitis: from basics to allergodromes. Pediatr Ann. 2009;38(2):99-108. ous occlusion of patent foramen ovale. by verbal explanations. Thorough edu- 5. Militello G, Jacob SE, Crawford GH. Allergic There are several case reports of severe cation is essential to clarify for the pa- contact dermatitis in children. Curr Opin Pediatr. systemic symptoms following placement tient what products, foods and medica- 2006;18(4):385-390. and nickel allergy requiring explanations are allowable in order to prevent 6. Valks R, Conde-Salazar L, Cuevas M. Allergic contact urticaria from natural rubber latex in health- 107–110 tion of the appliance. Nickel is also unnecessary invalidism. care and non-healthcare workers. Contact Dermatitis. thought to be responsible for a generalized Avoidance of specific allergens can 2004;50(4):222-224. eczematous dermatitis that developed in a be a painstaking task and discovering 7. Walsh ML, Smith VH, King CM. Type I and type patient after nitinol endograft placement sources of systemic exposure can be IV hypersensitivity to nickel. Australas J Dermatol. 2010;51(4):285-286. 111 for abdominal aortic aneurysm repair. an even more tedious process. There 8. Gimenez-Arnau A, Maurer M, De La Cuadra J, A host of different metals are used are programs available, however, to Maibach H. Immediate contact skin reactions, an up- regularly in arthroplastic surgery and aid in this endeavor. Both the Con- date of contact urticaria, contact urticaria syndrome and protein contact dermatitis: “a never ending story.” cutaneous complications are rare. They tact Allergen Management Program Eur J Dermatol. 2010;20(5):552-562. can include, however, overlying or gen- (CAMP), a service offered through the 9. Pirilä V. Endogenic contact eczema. Allerg Asthma eralized dermatitis, with metal allergy American Contact Dermatitis Society (Leipz). 1970;16(1):15-19. sometimes being implicated.112 The sub- (ACDS),116 and the Contact Allergen 10. Ratner JH, Spencer SK, Grainge JM. Cashew nut dermatitis: an example of internal-external contact-type ject of hypersensitivity reactions to im- Replacement Database (CARD), de- hypersensitivity. Arch Dermatol. 1974;110(6):921-923. 117 planted metal was recently reviewed by veloped by Mayo Clinic, provide 11. Fisher AA. Allergic dermatitis medicamentosa: the “sys- Basko-Plluska and colleagues.113 With information to help identify products temic contact-type variety.” Cutis. 1976;18(5):637-642. the field of “bionic parts” burgeoning, in which specific allergens may be 12. Nakayama H, Niki F, Shono M, Hada S. Mercury exanthem. Contact Dermatitis. 1983;9(5):411-417. the future may hold more reports of encountered. Both systems allow the 13. Menné T, Weismann K. [Hematogenous contact SCD related to implanted pulmonary, provider to enter a patient’s known eczema following oral administration of neomycin]. biliary, urologic and neurologic stents, contact allergens to generate a “shop- Hautarzt. 1984;35(6):319-320. shunts, stimulators and other devices. ping list” of products free of those par- 14. Andersen KE, Hjorth N, Menné T. The baboon syndrome: systemically-induced allergic contact der- ticular chemicals and cross-reactors. matitis. Contact Dermatitis. 1984;10(2):97-100. Role Of Patch Testing When systemic sources of relevant 15. Fisher AA. Systemic contact-type dermatitis due Patch testing is often necessary to diag- allergens are identified, they can usu- to drugs. Clin Dermatol. 1986;4(1):58-69. nose SCD and distinguish it from atopic ally be eliminated. Medications and 16. Happle R. [Paraptic eczema. Why a new name?]. Hautarzt. 1994;45(1):1-3. dermatitis, systemic drug eruption and personal products should be replaced 17. Bruze M. Systemically induced contact dermatitis non-compliance with allergen avoidance. by tolerated alternatives unrelated from dental rosin. Scand J Dent Res. 1994;102(6):376-378. Screening patch test arrays are available to to the sensitizing chemical. Often a 18. Menné T. Systemic contact dermatitis to hydroxyzine. Am J Contact Dermatitis. 1997;8(1):1. search for reactions to the most common 6-week diet is recommended, restrict- 19. Lachapelle J-M. Evolution of patch testing. Der- chemicals and generate clues for the pro- ing ingested sources of the allergen to matitis. 2009;20(6):316-321. vider as to potential sources. The North evaluate improvement. In the few cases 20. Häusermann P, Harr T, Bircher AJ. Baboon syn- American Standard Series includes al- where removal of allergen is impos- drome resulting from systemic drugs: is there strife between SDRIFE and allergic contact dermatitis lergens from several different categories, sible, medical management of the al- syndrome? Contact Dermatitis. 2004;51(5-6):297-310. and supplemental series, such as metal, lergic reaction can involve topical cor- 21. Thyssen JP, Maibach HI. Drug-elicited systemic aller- are also available. The reason to test with ticosteroids, the use of barrier devices, gic (contact) dermatitis--update and possible pathomech- supplemental allergens is to increase the systemic antihistamines, calcineurin anisms. Contact Dermatitis. 2008;59(4):195-202. 22. Jadassohn J. Zur kenntnis der medikamentössen der- chance of finding positive patch test re- inhibitors, UVB, UVA and, sometimes, matosen. Verhandlungen der Deutschen Dermatolo- actions that prove relevant.114 systemic immunosuppressants.118 n gischen Gesellschaft. Fünfter Kongress, Raz, 1895, Vienna: Braunmüller, 1896: p.106. Treatment Guidelines Dr. Silvestri is Associate Professor of Med- 23. Park RG. Cutaneous hypersensitivity to sulphon- amides. Br Med J. 1943;2(4306):69-72. Repeated exposure to allergens may icine and Director of the Contact Dermatitis 24. Leifer W. Contact dermatitis due to cinnamon: occur before sensitization develops and Clinic in the Division of Dermatology at recurrence of dermatitis following oral adminis-

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Allergen Focus tration of cinnamon oil. AMA Arch Derm Syphilol. 35. Silvestri DL, Barmettler S. Pruritus ani as a mani- 45. Veien NK, Hattel T, Justesen O, Nørholm A. Re- 1951;64(1):52-55. festation of systemic contact dermatitis: resolution with duction of intake of balsams in patients sensitive to 25. Cronin E. Contact dermatitis XVII: reactions to dietary nickel restriction. Dermatitis. 2011;22(1):50-55. balsam of Peru. Contact Dermatitis. 1985;12(5):270-273. contact allergens given orally or systemically. Br J Der- 36. Vermaat H, van Meurs T, Rustemeyer T, et al. Vul- 46. Audicana M, Bernedo N, Gonzalez I, et al. An un- matol. 1972;86(1):104-107. val allergic contact dermatitis due to peppermint oil usual case of baboon syndrome due to mercury pres- 26. Hjorth N. Contact dermatitis from vitamin B1 (thia- in herbal tea. Contact Dermatitis. 2008;58(6):364-365. ent in a homeopathic medicine. Contact Dermatitis. mine): relapse after ingestion of thiamine, cross-sensitization 37. Lucke TW, Fleming CJ, McHenry P, Lever R. 2001;45(3):185. to cocarboxylase. J Invest Dermatol. 1958;30(5):261-264. Patch testing in vulval dermatoses: how relevant is 47. Lerch M, Bircher AJ. Systemically induced al- 27. Wilson HT. Streptomycin dermatitis in nurses. Br nickel? Contact Dermatitis. 1998;38(2):111-112. lergic exanthem from mercury. Contact Dermatitis. Med J. 1958;1(5084):1378-1382. 38. Jensen CS, Menné T, Lisby S, et al. Experimental 2004;50(6):349-353. 28. Jacob SE, Zapolanski T. Systemic contact dermati- systemic contact dermatitis from nickel: a dose-re- 48. García-Menaya JM, Cordobés-Durán C, Bobadilla tis. Dermatitis. 2008;19(1):9-15. sponse study. Contact Dermatitis. 2003;49(3):124-132. P, et al. Baboon syndrome: 2 simultaneous cases in the 29. Saint-Mezard P, Berard F, Dubois B, et al. The role of 39. Veien NK, Hattel T, Justesen O, Nørholm A. Oral same family. Contact Dermatitis. 2008;58(2):108-109. CD4+ and CD8+ T cells in contact hypersensitivity and al- challenge with nickel and cobalt in patients with 49. Winnicki M, Shear NH. A systematic approach lergic contact dermatitis. Eur J Dermatol. 2004;14(3):131-138. positive patch tests to nickel and/or cobalt. Acta Derm to systemic contact dermatitis and symmetric 30. Möller H, Ohlsson K, Linder C, et al. The flare-up Venereol. 1987;67(4):321-325. drug-related intertriginous and flexural exanthema reactions after systemic provocation in contact allergy to 40. Veien NK, Hattel T, Laurberg G. Placebo-controlled (SDRIFE): a closer look at these conditions and an nickel and gold. Contact Dermatitis. 1999;40(4):200-204. oral challenge with cobalt in patients with positive patch approach to intertriginous eruptions. Am J Clin Der- 31. Isaksson M, Bruze M. Allergic contact dermatitis tests to cobalt. Contact Dermatitis. 1995;33(1):54-55. matol. 2011;12(3):171-180. in response to budesonide reactivated by inhalation of 41. Stuckert J, Nedorost S. Low-cobalt diet for dyshidrotic 50. Yu Y, Scheinman PL. Lip and perioral dermatitis the allergen. J Am Acad Dermatol. 2002;46(6):880-885. eczema patients. Contact Dermatitis. 2008;59(6):361-365. caused by propyl gallate. Dermatitis. 2010;21(2):118-119. 32. Giordano-Labadie F, Pech-Ormieres C, Bazex J. 42. Veien NK, Kaaber K. Nickel, cobalt and chro- 51. Szyfelbein Masterpol K, Gottlieb AB, Scheinman Systemic contact dermatitis from sorbic acid. Contact mium sensitivity in patients with pompholyx (dyshi- PL. Systemic contact dermatitis presenting as lichen Dermatitis. 1996;34(1):61-62. drotic eczema). Contact Dermatitis. 1979;5(6):371-374. planus of the lip. Dermatitis. 2010;21(4):218-219. 33. Fisher AA. Systemic contact dermatitis due to in- 43. Nielsen GD, Jepsen LV, Jørgensen PJ, et al. Nickel- 52. Matiz C, Jacob SE. Systemic contact dermatitis in travenous Valium in a person sensitive to propylene sensitive patients with vesicular hand eczema: oral children: how an avoidance diet can make a differ- glycol. Cutis. 1995;55(6):327-328. challenge with a diet naturally high in nickel. Br J ence. Pediatr Dermatol. 2011;28(4):368-374. 34. Vermaat H, Smienk F, Rustemeyer T, et al. Ano- Dermatol. 1990;122(3):299-308. 53. Hill AM, Belsito DV. Systemic contact dermatitis genital allergic contact dermatitis: the role of spices and 44. Niinimäki A. Delayed-type allergy to spices. Con- of the eyelids caused by formaldehyde derived from flavour allergy. Contact Dermatitis. 2008;59(4):233-237. tact Dermatitis. 1984;11(1):34-40. aspartame? Contact Dermatitis. 2003;49(5):258-259.

TrianexTM 0.05% (Triamcinolone Studies to determine mutagenicity with prednisolone and hydrocortisone have revealed Acetonide Ointment) Rx Only negative results. INDICATIONS AND USAGE Pregnancy Category C TrianexTM 0.05% (Triamcinolone Acetonide Ointment) is indicated for the relief of the Corticosteroids are generally teratogenic in laboratory animals when administered inflammatory and pruriticmanifestations of corticosteroid responsive dermatoses. systemically at relatively low dosage levels. The more potent corticosteroids have been CONTRAINDICATIONS shown to be teratogenic after dermal application in laboratory animals. There are no adequate and well-controlled studies in pregnant women on teratogenic effects from TrianexTM 0.05% (Triamcinolone Acetonide Ointment) is contraindicated in those patients topically applied corticosteroids. Therefore, topical corticosteroids should be used during with a history of hypersensitivity to any of the components of the preparation. pregnancy only if the potential benefit justifies the potential risk to the fetus. Drugs of PRECAUTIONS this class should not be used extensively on pregnant patients, in large amounts, or for General prolonged periods of time. Systemic absorption of topical corticosteroids has produced reversible Nursing Mothers hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushing’s It is not known whether topical administration of corticosteroids could result in sufficient syndrome, hyperglycemia, and glucosuria in some patients. systemic absorption to produce detectable quantities in breast milk. Systemically Conditions which augment systemic absorption include the application of the more administered corticosteroids are secreted into breast milk in quantities not likely to have potent steroids, use over large surface areas, prolonged use, and the addition of occlusive a deleterious effect on the infant. Nevertheless, caution should be exercised when topical dressings. corticosteroids are administered to a nursing woman. Therefore, patients receiving a large dose of a potent topical steroid applied to a large Pediatric Use surface area or under an occlusive dressing should be evaluated periodically for evidence Pediatric patients may demonstrate greater susceptibility to topical of HPA axis suppression by using the urinary free cortisol and ACTH stimulation tests. If corticosteroid-induced HPA axis suppression and Cushing’s syndrome than mature HPA axis suppression is noted, an attempt should be made to withdraw the drug, to reduce patients because of a larger skin surface area to body weight ratio. the frequency of application, or to substitute a less potent steroid. Hypothalamic-pituitary-adrenal (HPA) axis suppression, Cushing’s syndrome and intracranial Recovery of HPA axis function is generally prompt and complete upon discontinuation of hypertension have been reported in children receiving topical corticosteroids. Manifestations the drug. Infrequently, signs and symptoms of steroid withdrawal may occur, requiring of adrenal suppression in children include linear growth retardation, delayed weight gain, supplemental systemic corticosteroids. low plasma cortisol levels, and absence of response to ACTH stimulation. Manifestations of Children may absorb proportionally larger amounts of topical corticosteroids and thus be intracranial hypertension include bulging fontanelles, headaches, and bilateral papilledema. more susceptible to systemic toxicity (see PRECAUTIONS-Pediatric Use). Administration of topical corticosteroids to children should be limited to the least amount If irritation develops, topical corticosteroids should be discontinued and appropriate compatible with an effective therapeutic regimen. Chronic corticosteroid therapy may therapy instituted. interfere with the growth and development of children. In the presence of dermatological infections, the use of an appropriate antifungal or ADVERSE REACTIONS antibacterial agent should be instituted. If a favorable response does not occur promptly, The following local adverse reactions are reported infrequently with topical corticosteroids, the corticosteroid should be discontinued until the infection has been adequately but may occur more frequently with the use of occlusive dressings. These reactions are controlled. listed in an approximate decreasing order of occurrence: Information for the Patient Burning, Itching, Irritation, Dryness, Folliculitis, Hypertrichosis, Acneiform eruptions, Patients using topical corticosteroids should receive the following information and Hypopigmentation, Perioral dermatitis, Allergic contact dermatitis, Maceration of the skin, instructions: Secondary infection, Skin atrophy, Striae, Miliaria. 1. This medication is to be used as directed by the physician. It is for external use only. OVERDOSAGE Avoid contact with the eyes. Topically applied corticosteroids can be absorbed in sufficient amounts to produce systemic effects (see PRECAUTIONS). 2. Patients should be advised not to use this medication for any disorder other than that for which it was prescribed. DOSAGE AND ADMINISTRATION TM 3. The treated skin area should not be bandaged or otherwise covered or wrapped so as Trianex 0.05% (Triamcinolone Acetonide Ointment, USP) is generally applied to the to be occlusive unless directed by the physician. affected area as a thin film from two to four times daily depending on the severity of the condition. 4. Patients should report any signs of local adverse reactions especially under occlusive dressing. Occlusive dressings may be used for the management of psoriasis or recalcitrant conditions. 5. Parents of pediatric patients should be advised not to use tight-fitting diapers or plastic pants on a child being treated in the diaper area, as these garments may constitute If an infection develops, the use of occlusive dressings should be discontinued and occlusive dressings. appropriate antimicrobial therapy instituted. Laboratory Tests CAUTION: The following tests may be helpful in evaluating the HPA axis suppression: For external use only. Not for ophthalmic use. Urinary free cortisol test ACTH stimulation test Distributed by: UPSHER-SMITH LABORATORIES, INC. Carcinogenesis and Mutagenesis and Impairment of Fertility Minneapolis, MN 55447 Long-term animal studies have not been performed to evaluate the carcinogenic potential or the effect on fertility of topical corticosteroids. 104577-01 Revised: September 2010

104577_01_PI_2_3pgAd.indd 1 7/26/11 6:28 PM Allergen Focus

54. Hjorth N. Eczematous allergy to balsams, allied Allergic contact dermatitis to propolis and carnauba 103. Zabel M, Lindscheid KR, Mark H. [Copper sul- perfumes and flavouring agents, with special reference wax from lip balm and chewable vitamins in a child. fate allergy with special reference to internal expo- to balsam of Peru. Acta Derm Venereol Suppl (Stockh). Contact Dermatitis. 2008;58(4):242-243. sure]. Z Hautkr. 1990;65(5):481-482, 485-486. 1961;41(Suppl 46):1-216. 79. Komericki P, Kränke B. Maculopapular exanthem 104. Purello D’Ambrosio F, Ricciardi L, Isola S, et 55. Veien NK, Hattel T, Justesen O, Nørholm N. Oral from propolis: case report and review of systemic cu- al. Systemic contact dermatitis to copper-containing challenge with balsam of Peru. Contact Dermatitis. taneous and non-cutaneous reactions. Contact Derma- IUD. Allergy. 1996;51(9):658-659. 1985;12(2):104-107. titis. 2009;61(6):353-355. 105. Pujol RM, Randazzo L, Miralles J, Alomar A. 56. Veien NK. Systemically induced eczema in adults. 80. Morrow DM, Rapaport MJ, Strick RA. Hypersen- Perimenstrual dermatitis secondary to a copper- Acta Derm Venereol Suppl (Stockh). 1989;147:1-58. sitivity to aloe. Arch Dermatol. 1980;116(9):1064-1065. containing intrauterine contraceptive device. Contact 57. Jensen CS, Menné T, Johansen JD. Systemic con- 81. Petrozzi JW, Shore RN. Generalized exfolia- Dermatitis. 1998;38(5):288. tact dermatitis after oral exposure to nickel: a review tive dermatitis from ethylenediamine. Arch Dermatol. 106. Al-Safi Z, Shavell VI, Katz LE, Berman JM. Nickel with a modified meta-analysis. Contact Dermatitis. 1976;112(4):525-526. hypersensitivity associated with an intratubal microin- 2006;54(2):79-86. 82. Guin JD, Fields P, Thomas KL. Baboon syndrome sert system. Obstet Gynecol. 2011;117(2 Pt 2):461-462. 58. Veien NK, Hattel T, Laurberg G. Low nickel from i.v. aminophylline in a patient allergic to ethyl- 107. Fukahara K, Minami K, Reiss N, et al. Systemic al- diet: an open, prospective trial. J Am Acad Dermatol. enediamine. Contact Dermatitis. 1999;40(3):170-171. lergic reaction to the percutaneous patent foramen ovale 1993;29(6):1002-1007. 83. Walker SL, Ferguson JE. Systemic allergic contact der- occluder. J Thorac Cardiovasc Surg. 2003;125(1):213-214. 59. Krecisz B, Chomiczewska D, Kiec-Swierczynska matitis due to ethylenediamine following administration 108. Dasika UK, Kanter KR, Vincent R. Nickel al- M, Kaszuba A. Systemic contact dermatitis to nickel of oral aminophylline. Br J Dermatol. 2004;150(3):594. lergy to the percutaneous patent foramen ovale oc- present in cocoa in 14-year-old boy. Pediatr Dermatol. 84. Sasseville D. Neomycin. Dermatitis. 2010;21(1):3-7. cluder and subsequent systemic nickel allergy. J Thorac 2011;28(3):335-336. 85. Guin JD, Phillips D. Erythroderma from systemic Cardiovasc Surg. 2003;126(6):2112. 60. de Medeiros LM, Fransway AF, Taylor JS, et al. contact dermatitis: a complication of systemic genta- 109. Wertman B, Azarbal B, Riedl M, Tobis J. Adverse Complementary and alternative remedies: an addi- micin in a patient with contact allergy to neomycin. events associated with nickel allergy in patients undergo- tional source of potential systemic nickel exposure. Cutis. 1989;43(6):564-567. ing percutaneous atrial septal defect or patent foramen Contact Dermatitis. 2008;58(2):97-100. 86. Morton CA, Evans CD, Douglas WS. Allergic con- ovale closure. J Am Coll Cardiol. 2006;47(6):1226-1227. 61. Kaaber K, Veien NK. The significance of chromate tact dermatitis following subconjunctival injection of 110. Rabkin DG, Whitehead KJ, Michaels AD, et al. ingestion in patients allergic to chromate. Acta Derm framycetin. Contact Dermatitis. 1993;29(1):42-43. Unusual presentation of nickel allergy requiring ex- Venereol. 1977;57(4):321-323. 87. Haeberle M, Wittner B. Is gentamicin-loaded plantation of an Amplatzer atrial septal occluder de- 62. Veien NK, Hattel T, Laurberg G. Chromate-aller- bone cement a risk for developing systemic allergic vice. Clin Cardiol. 2009;32(8):E55-57. gic patients challenged orally with potassium dichro- dermatitis? Contact Dermatitis. 2009;60(3):176-177. 111. Giménez-Arnau A, Riambau V, Serra-Baldrich mate. Contact Dermatitis. 1994;31(3):137-139. 88. Fernandez Redondo V, Casas L, Taboada M, To- E, Camarasa JG. Metal-induced generalized pru- 63. Ozkaya E, Topkarci Z, Ozarmagan G. Systemic al- ribio J. Systemic contact dermatitis from erythromy- riginous dermatitis and endovascular surgery. Contact lergic dermatitis from chromium in a multivitamin/ cin. Contact Dermatitis. 1994;30(5):311. Dermatitis. 2000;43(1):35-40. multimineral tablet. Contact Dermatitis. 2010;62(3):184. 89. Vernassiere C, Barbaud A, Trechot PH, et al. Sys- 112. Thyssen JP, Menné T, Schalock PC, et al. Prag- 64. Fowler JF. Systemic contact dermatitis caused by temic acyclovir reaction subsequent to acyclovir con- matic approach to the clinical work-up of patients oral chromium picolinate. Cutis. 2000;65(2):116. tact allergy: which systemic antiviral drug should then with putative allergic disease to metallic orthopae- 65. Pfützner W, Thomas P, Niedermeier A, et al. Sys- be used? Contact Dermatitis. 2003;49(3):155-157. dic implants before and after surgery. Br J Dermatol. temic contact dermatitis elicited by oral intake of Bal- 90. Möller H, Björkner B, Bruze M. Clinical reactions 2011;164(3):473-478. sam of Peru. Acta Derm Venereol. 2003;83(4):294-295. to systemic provocation with gold sodium thiomalate 113. Basko-Plluska JL, Thyssen JP, Schalock PC. Cuta- 66. Veien NK. Ingested food in systemic allergic con- in patients with contact allergy to gold. Br J Dermatol. neous and systemic hypersensitivity reactions to me- tact dermatitis. Clin Dermatol. 1997;15(4):547-555. 1996;135(3):423-427. tallic implants. Dermatitis. 2011;22(2):65-79. 67. Castanedo-Tardan MP, González ME, Connelly EA, 91. Rajpar SF, Foulds IS, Abdullah A, Maheshwari M. Se- 114. Nijhawan RI, Jacob SE. Patch testing: the whole et al. Systematized contact dermatitis and montelukast vere adverse cutaneous reaction to insulin due to cresol in addition to the sum of its parts is greatest. Dermati- in an atopic boy. Pediatr Dermatol. 2009;26(6):739-743. sensitivity. Contact Dermatitis. 2006;55(2):119-120. tis. 2009;20(1):58-59. 68. Cashman AL, Warshaw EM. Parabens: a review of 92. Quirce S, Alvarez MJ, Olaguibel JM, Tabar AI. Sys- 115. Encarnación LA, Celis-Versoza M. Con- epidemiology, structure, allergenicity, and hormonal temic contact dermatitis from oral prednisone. Con- tact allergy presenting as erythroderma. Dermatitis. properties. Dermatitis. 2005;16(2):57-66. tact Dermatitis. 1994;30(1):53-54. 2006;17(1):45-47. 69. Veien NK, Hattel T, Laurberg G. Oral challenge 93. Whitmore SE. Delayed systemic allergic reactions to 116. ACDS CAMP: American Contact Dermatitis with parabens in paraben-sensitive patients. Contact corticosteroids. Contact Dermatitis. 1995;32(4):193-198. Society. 2011. Available at: http://www.contactderm. Dermatitis. 1996;34(6):433. 94. Isaksson M. Systemic contact allergy to corticoste- org/i4a/pages/index.cfm?pageid=3489. Accessed 70. Kaminer Y, Apter A, Tyano S, et al. Delayed hyper- roids revisited. Contact Dermatitis. 2007;57(6):386-388. September 21, 2011. sensitivity reaction to orally administered methylpara- 95. Mahajan VK, Sharma NL, Sharma RC. Parthe- 117. CARD: Contact Allergen Replacement Data- ben. Clin Pharm. 1982;1(5):469-470. nium dermatitis: is it a systemic contact dermatitis base. 2011. Available at: http://www.preventice.com/ 71. Sánchez-Pérez J, Diez MB, Pérez AA, et al. Aller- or an airborne contact dermatitis? Contact Dermatitis. card/. Accessed September 21, 2011. gic and systemic contact dermatitis to methylparaben. 2004;51(5-6):231-234. 118. Mark BJ, Slavin RG. Allergic contact dermatitis. Contact Dermatitis. 2006;54(2):117-118. 96. Nijhawan RI, Molenda M, Zirwas MJ, Jacob Med Clin North Am. 2006;90(1):169-185. 72. Hannuksela M, Förström L. Reactions to peroral SE. Systemic contact dermatitis. Dermatol Clin. propylene glycol. Contact Dermatitis. 1978;4(1):41-45. 2009;27(3):355-364. Dr. Jacob, the Section 73. Lowther A, McCormick T, Nedorost S. Systemic 97. Lomaga MA, Polak S, Grushka M, Walsh S. Re- Editor of Allergen Focus, contact dermatitis from propylene glycol. Dermatitis. sults of patch testing in patients diagnosed with oral 2008;19(2):105-108. lichen planus. J Cutan Med Surg. 2009;13(2):88-95. directs the contact derma- 74. Oliwiecki S, Beck MH, Hausen BM. Compositae 98. Trombelli L, Virgili A, Corazza M, Lucci R. Sys- titis clinic at Rady Chil- dermatitis aggravated by eating lettuce. Contact Der- temic contact dermatitis from an orthodontic appli- dren’s Hospital – Univer- matitis. 1991;24(4):318-319. ance. Contact Dermatitis. 1992;27(4):259-260. sity of California in San 75. Wintzen M, Donker AS, van Zuuren EJ. Recalci- 99. Pigatto PD, Guzzi G. Systemic contact dermatitis trant atopic dermatitis due to allergy to Compositae. from nickel associated with orthodontic appliances. Section Editor: Diego, CA. She is also Contact Dermatitis. 2003;48(2):87-88. Contact Dermatitis. 2004;50(2):100-101. Sharon E. Jacob, MD Associate Clinical Profes- 76. Rodríguez-Serna M, Sánchez-Motilla JM, 100. Schultz JC, Connelly E, Glesne L, Warshaw EM. sor of Pediatrics and Med- Ramón R, Aliaga A. Allergic and systemic contact Cutaneous and oral eruption from oral exposure to icine WOS (Dermatology) at the University dermatitis from Matricaria chamomilla tea. Contact nickel in dental braces. Dermatitis. 2004;15(3):154-157. Dermatitis. 1998;39(4):192-193. 101. Barranco VP. Eczematous dermatitis caused by internal of California, San Diego. 77. Paulsen E. Contact sensitization from Composi- exposure to copper. Arch Dermatol. 1972;106(3):386-387. tae-containing herbal remedies and cosmetics. Contact 102. Rongioletti F, Rivara G, Rebora A. Contact der- Dermatitis. 2002;47(4):189-198. matitis to a copper-containing intra-uterine device. Disclosure: Dr. Jacob is the principal investiga- 78. Jacob SE, Chimento S, Castanedo-Tardan MP. Contact Dermatitis. 1985;13(5):343. tor for Smartchoice USA PREA-2 trial.

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