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Thimerosal Red Pigmentation

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Thimerosal Red Pigmentation this is beyond the scope of this section, we acknowledge this form of hypersen- sitivity due to the severity of the poten- tial reactions and direct the reader to key sources.1,2 Focus Allergic contact dermatitis represents a ALLERGEN T helper cell Type 1 (Th1) dependent delayed-type (Type IV) hypersensitivity reaction. The instigating exogenous antigens are primarily small lipophilic chemicals (haptens) with a molecular weight less than 500 Da. Unlike other haptens, metal antigens do not covalently bind to carrier pro- teins; instead they complex with pro- teins similar to the binding of cobalt 1 and vitamin B12. On direct antigen exposure to the skin or mucosa, an immunologic cas- cade is initiated that includes cytokines, i.e. interleukin 2 (IL-2) and interferon gamma (IFN-γ), T cells and Langerhan cells. This complex interaction leads to the clinical picture of ACD, an impor- tant disease with high impact both in terms of patient morbidity and eco- nomics. The primary focus of this section is to highlight the educational component of allergic contact dermatitis. CLINICAL ILLUSTRATION A woman presented to the University of Miami Contact Dermatitis Clinic Focus on T.R.U.E. Test Allergens #23: with a 6-year history of generalized pruritus and inflammation of her eyelids treated unsuccessfully with antihista- mines and topical corticosteroids. Of note, she also had a small tattoo with a papular reaction in the area of Thimerosal red pigmentation. She did not know the ink constituents. BY SHARON E. JACOB, M.D., AND RAN HUO, B.S. THE HISTORY OF THIMEROSAL Thimerosal, C9H9HgNaO2S, is a llergic contact dermatitis (ACD) is an important disease mercuric derivative of thiosalicyclic with high impact both in terms of patient morbidity and acid that goes by many names (see Table A economics. The contact dermatitides include allergic 1). It has been used as a disinfectant contact dermatitis, irritant contact dermatitis and contact (Merthiolate) and a preservative in urticaria. some vaccines, cosmetics, tattoo inks, Irritant contact dermatitis, the most common form, accounts eye drops and contact lens solutions. for approximately 80% of environmental- and occupational- The FDA banned the sale of topical- based dermatoses. ly applied thimerosal antibiotics in the Contact urticaria (wheal and flare reaction) represents an IgE 1980s due to severe, even crippling, and mast cell-mediated immediate-type hypersensitivity reaction that can lead to adverse skin reactions in sensitive indi- anaphylaxis; the foremost example of this would be latex hypersensitivity.Although viduals. And, in July 1999, the U.S. 16 JANUARY 2006 SKIN & AGING TABLE 1 chosis. Because of the major neurologi- ported “Lewis and Clark latrines” COMMON SYNONYMS OF THIMEROSAL cal risk mercury poses to the unborn around the country have uncovered the fetus, pregnant women are cautioned to locations of their campsites.7 • Ethyl (2-mercaptobenzoato-S) limit the consumption of high mercu- Mercury is a bioaccumulative toxin mercury sodium salt ry-containing fish to just once a month. that is readily absorbed through the • Mercurochrome Cutaneous changes may include con- skin, respiratory and gastrointestinal sys- 8 • Mercurothiolate tact dermatitis, burning of the face, grey tems. Methyl mercury in the environ- or blue-black facial discoloration, flush- ment works its way up the food chain in • Merfamin ing, erythroderma, purpura and gin- fish through bioaccumulation, reaching • Merthiolate givostomatitis.5 especially high levels in larger species • Mertorgan such as shark (0.99 parts per million, or MERCURY IN THE ENVIRONMENT ppm), swordfish (0.97 ppm), and tuna • Merzonin Mercury pollution in the environ- (0.38 ppm). • Sodium ethylmercurithiosalicylate ment has increased threefold since the FDA toxicologists recommend limit- • Thiomersal industrial revolution, with soil deposi- ing the consumption of shark and • Thiomersalan tion rates ranging from 5 to swordfish to 7 ounces (one serving) a 15 µg/m2/year.6 week, and the consumption of fresh • Thiomersalate The major sources of environmental tuna to 14 ounces a week (canned tuna • [(o-carboxyphenyl)thio] Ethylmercury sodium salt mercury are coal-fired power plants, has around half the methyl mercury metal smelting, gold production, and content of fresh tuna). Other animals that may accumulate mercury include sea birds (that feed on mercury contam- Department of Health mandated the inated fish). reduction of thimerosal in routine pedi- The U.S. Environmental Protection atric vaccines. Agency (EPA) limit for mercury con- In 2004, California and Iowa passed THE LEWIS AND CLARK tent in tap water is 2 parts per billion bans of mercury in all vaccinations, and (ppb), while the limit for cosmetics is 65 seven other states have similar legisla- PIONEERS WERE ppm (21CFR700.13).The average daily tion in progress.3 KNOWN TO INGEST mercury exposure from tap water and The main concern with thimerosal air in the general population is a thou- involves its metabolite — ethyl mercu- “THUNDERCLAPPERS” sand-fold less than that from seafood ry.Hat makers, or “hatters” in the 1800s intake.9 were notorious for suffering from (PILLS NEARLY No correlations have been published dementias due to the mercury nitrate 60% CONCENTRATED regarding mercury content in tap water used in felt processing. This mercury- and allergic contact dermatitis. associated dementia in felt workers was MERCURY) FOR the inspiration for the Mad Hatter in HOTLY DEBATED LINK Lewis Carroll’s Alice in Wonderland and GASTROINTESTINAL Just how similar the effects of ethyl the origin of the phrase “mad as a hat- AILMENTS. mercury (from thimerosal) and methyl ter”. The Mad Hatter’s disease, also mercury are on the human body is the known as erythrism, includes a constel- subject of much debate, with research lation of dementia, stomatitis, muscle suggesting that ethyl mercury stays in spasm, tremor and skin rashes.4 the body for a shorter period of time The ethyl mercury from thimerosal is and is generally less harmful. chemically similar to methyl mercury, the disposal (storing in landfills, inciner- Research is underway at the National which is 5 to 20 times as toxic as inor- ating) of mercury containing products Institutes of Health to determine the ganic mercury in its effects on the such as batteries, fluorescent bulbs and safety guidelines for thimerosal in the human central nervous and endocrine thermometers. hotly debated questionable link systems. Of historical interest, the persistence between thimerosal and the develop- Acute or chronic exposure to organ- of mercury in the soil allowed archeol- ment of childhood neurological prob- ic and inorganic mercury can result in ogists studying the Lewis and Clark lems, such as autism.10-13 renal, neurologic and dermal toxicity. expedition insight into the trail route. While most patients do not experi- Neurologic and psychiatric sequelae During their travels, the Lewis and ence an immediate allergic reaction to include tremor, muscle weakness, Clark pioneers were known to ingest thimerosal-containing intramuscular peripheral neuropathy, metallic taste, “Thunderclappers” (pills nearly 60% vaccines, the potential remains for hypersalivation, memory loss, ery- concentrated mercury) for gastrointesti- delayed hypersensitivity and toxic sys- thrism, depression, anxiety and psy- nal ailments. Traces of mercury in pur- temic effects. JANUARY 2006 SKIN & AGING 17 TABLE 2 gens are often used in combination PRODUCTS CONTAINING THIMEROSAL/MERCURY with one another in products and co- sensitization occurs.16 ANTIBIOTICS FOR THE EYE Cortisporin Ophthalmic Suspension; Thimerosal-sensitive patients can Neosporin Ophthalmic Solution either be allergic to the mercuric moi- ety (most common) or the thiosalicylic CONTACT LENS SOLUTION Bausch & Lomb Sterile Preserved Saline Solution, Allergan acid moiety (these patients are advised Hydrocare, Advanced Medical Optics LC-65, Ocufen to avoid piroxicam, which also contains this moiety).17,18 TOPICAL MEDICATIONS, Mercurochrome (banned in the United States, Cinnabar (mercuric sulfide) used in ANTI-FUNGALS, ANTISEPTIC SPRAYS but used in other countries as antiseptic), red tattoo inks can lead to allergic reac- Merchromine tions and scarring.Tsuruta et al. report- ed a case of a 40-year-old Japanese man HORMONE INJECTIONS Testaqua, Testamone with a red tattoo who developed a NASAL PREPARATIONS Nasal Moist AF; Neo-Synephrine Pediatric Formula, Mild whole-body rash after eating 250 g of raw swordfish and alfonsino.19 In this Formula, Regular Strength, and Extra Strength Nasal Spray case the mercuric tattoo pigments EAR PREPARATIONS Coly-mycin S Otic; Cortisporin Otic Suspension; caused the initial sensitization to mer- Pediotic Suspension cury in the patient, producing a delayed hypersensitivity reaction. COSMETICS, BLEACHING CREAMS L’Oreal Miracle Wear Mascara, Stagelight Mascara, Miss Key Subsequent exposure of the patient to Whitening Cream, Crema Santa, Dermaline Cream, Crema de mercury-containing products either Belleza (all banned in the United States, but still being sold)21 through ingestion/inhalation/injection (mercury vapor, mercury-laden fish, VACCINES Engerix-B, FluShield and Fluzone, Hep-B-Gammagee, HyperHEP, vaccines, toxoids, amalgam dental HyperTET Tetanus and diphtheria toxoids, Menactra, Menomune, fillings) or direct contact (mercury- Recombivax HB containing creams, contact lens solution) precipitated the allergic contact TATTOO INK Cinnabar (mercuric sulfide) dermatitis. While the ink compositions
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