Allergic contact dermatitis (ACD) is an important disease that notably affects 14.5 million Americans each year.1 Due to overwhelming patient morbidity, loss of school and work time and significant expenditures for healthcare visits and medicaments, ACD presents with a high economic burden. A correct diagnosis of ACD will improve, prevent or ”cure” the dermatitis and decrease overall costs to the healthcare system.1 Once patch testing is performed and a culprit has been identified, education becomes the critical intervention to ensure adherence to an avoidance regimen. With allergen avoidance, remission of the dermatitis ensues. Patients who are unable to comply with avoidance regimens are at risk for recurrent or sustained dermatitis or progression to a systematized presentation.2,3
The 2 main types of contact dermatitis are irritant and allergic, with irritant contact dermatitis (ICD) being the most common. ICD may occur in anyone who is exposed to an irritating substance with significant duration or in significant concentrations such as chronic or frequent water exposure, abrasive cleansers, detergents and soaps. It is important to note that ICD can at times precede or be a concomitant diagnosis with ACD.4,5 ACD represents a T helper cell type 1 dependent delayed-type hypersensitivity reaction that can occur to a large number of chemicals from poison ivy to metals to fragrances. These instigating exogenous antigens are primarily small lipophilic chemicals (haptens) with a molecular weight less than 500 Da. However, metals do not covalently bind to carrier proteins, instead they complex with proteins similar to the binding of cobalt and vitamin B12.6 On direct antigen exposure to the skin or mucosa, an immunologic cascade is initiated which includes cytokines, such as interleukin 2 and interferon gamma, T cells and dendritic cells. This complex interaction is the basis for the clinical expression of ACD.
The evaluation of ACD fits well with theranostic theory, as the epicutaneous patch test diagnostic evaluation dictates the avoidance management in each individual patient. Although ACD is not “curable,” many individuals will achieve complete remission with assiduous avoidance. In this article, we focus on the element cobalt. We also explore top relevant allergens, regional- and topic-based dermatitis presentations and clinical tips and pearls for diagnosis and treatment.
Cobalt was prized for its blue pigment by ancient civilizations. The earliest object containing cobalt is dated to around 2000 bc from a site in Southern Mesopotamia called Eridu.7 Ancient Egyptians created blue pottery as early as 1550 bc. Analysis of the pottery demonstrated that cobalt was in composition with manganese, nickel and zinc which is thought to have been mined in the desert oases of Dakleh.8 In other parts of the world, cobalt had been identified as giving blue colors to pottery and statues of horses dating back to the 6th century ad in China during the Tang dynasty.9 Of interest, none of these civilizations knew what compound was giving the vibrant and desired blue hue, for the element ‘cobalt’ was not discovered until 1735.
The legend behind the element cobalt comes from Saxony lore; in the Schneedburg Mountains, miners worked day and night in order to procure the precious mineral silver. Many were wary of evil spirits and goblins, that they named Kobolds (circa 1335). The Kobolds were thought to live inside the mountain and when miners encountered problems the Kobolds would often be blamed.10 For example, Kobolds were credited when the miners hands had a burning sensation after working long days.11 Later the term Kobold became associated with the ore that created toxic fumes while smelting to make silver, due to the release of arsenic.
In 1735 Georg Brandt, a Swedish chemist, while experimenting with the ore, discovered the very substance that was giving off the blue color. Due to the folklore associated with its history, the metal was named cobalt to denote “King Goblin,” but it was not until 1780 that cobalt was proven to be a single metal element.12 More than 2 decades later, Louis Jaques Thenard of France revolutionized the ability to utilize cobalt for commercial interest. He discovered how to make “cobalt blue” by heating alumina with cobalt phosphate at high temperatures, which catalyzed the formation of the notably blue cobalt oxide. In honor of his discovery, the color became known as Thenard’s blue.13
Cobalt’s Properties, Occurrences and Uses
The chemical element cobalt is a rare element that only makes up 0.001% of the earth’s crust. It is a brittle, hard white metal that may be found naturally in soil, dust and seawater. However, it is very rarely found in its pure form when mined from the earth, as it is normally produced as a byproduct of iron, nickel, copper and silver mining. Cobalt has several unique properties other than giving off a blue color that distinguish it from other elements. It is 1 of only 3 metals that has magnetic properties at room temperature.9 Furthermore, cobalt is required in the synthesis of vitamin B12, appropriately named cobalamin. Vitamin B12 contains a trivalent cobalt and thus cobalt is an essential trace mineral for all animals.14 Although cobalt is found throughout the world, approximately 50% of it is obtained from Africa, mainly in association with mining for nickel ore.10
While it is procured as a secondary mining product, cobalt has its own significant value. It is used in the production of high performance alloys, which when combined with other materials, to change the strength, are utilized in joint replacements, aircraft parts, dental prosthesis, magnets, cutting tools and drills. One of cobalt’s isotopes, Cobalt 60 has also been used to deliver treatments in radiation oncology. Recently with the surging advance of portable electronics and mobile devices, cobalt is becoming more frequently used in rechargeable batteries, including lithium, nickel-cadmium and nickel-metal hydride batteries. The Table highlights the top relevant sources of cobalt in causing ACD.
Cobalt in Dentistry
Cavities in teeth have been filled since the 16th century with early materials including lead, cork, stone chips and gold foil. With the invention of the dental drill in 1871, there was an increased demand for inexpensive fillings.15 And, in 1895 came the development of the alloy mixture, which we know today as dental amalgam. It is typically composed of 50% pure elemental mercury along with varying smaller amounts of silver, tin, copper and zinc. The silver metal powder reacts with liquid mercury to produce a maleable alloy that can be easily packed and shaped. Notably, this base is often modified with materials such as cobalt to increase resistance to enzymatic breakdown, a reliable feature for prosthesis, dental fillings, crowns, bridges and dentures.
Cobalt has been implicated in amalgam and dental crown related oral and generalized hypersensitivity reactions, in addition to dyshidrotic eczema, for which cobalt-restriction diets have been implemented.16-18 However, unlike the other metal associated ACD, the diagnosis of cobalt allergy may be more difficult to make. Due to its association with nickel and its frequent combination with nickel in alloys, it is speculated that the cobalt-specific allergic reactions are often secondary to co-sensitization with nickel.19 Thus, a pure sample of nickel-free cobalt is essential in an epicutaneous patch test to establish an accurate diagnosis of cobalt ACD.
Cobalt Causing Systemic Toxicity:
Brew to Joints
The first documented systemic toxicity related to cobalt was termed the “Quebec beer-drinkers cardiomyopathy.” In 1966, strange cases of rapidly progressing and often fatal cardiomyopathy began occurring in Quebec, Canada. It was known that all of the affected patients were heavy beer drinkers, but the rapid onset in symptoms was very unusual for cardiomyopathy occurring due to alcohol alone. An intense investigation suggested that the likely culprit for the outbreak was cobalt. It was found that cobalt had been added to both bottled and draft beer in order to decrease foam production. Although the exact mechanism behind cobalt causing these deaths was not elucidated, removal of the cobalt from beer resulted in no further cases being reported.20 The myocardial damage from cobalt may be due to mitochondrial damage from heavy metal oxidative phosphorylation. Other systemic problems that can be seen include thyroid, liver, neurologic and bone marrow dysfunction.
Currently, there is much debate regarding potential toxicity after getting metal-on-metal (MoM) joint replacements. MoM replacements containing a cobalt-chromium alloy for both the lining of the head and cup/ball of the prosthesis have been used instead of the traditional ceramic or polyethylene material. They were developed for increased durability, a larger size increasing joint stability and less debris wear than implants made from other sources. Although they were developed to last longer and be overall better for patients there is now data that they may be associated with increased failure rates. There is the potential for the metal ions to locally react to surrounding tissues or cause systemic problems in certain individuals.21
Due to these potential issues, some European countries have recently recommend lifelong yearly follow-up of patients with MoM, which includes both imaging and serum cobalt/chromium levels.21 The FDA currently recommends imaging and serum metal ion testing for any patients that are exhibiting signs that their MoM device is not functioning properly or if a patient is having concerning symptoms. However, the agency does not feel that there is sufficient evidence to test patients who are asymptomatic or have good function with the MoM device.22 Notably, the cobalt MoM devices are a growing source of litigation settlements.
Practicals of Patch Testing
Patch testing is often necessary to confirm the diagnosis of ACD and to identify the relevant allergen(s) responsible. Screening patch test trays are available, which isolate the most common chemicals and offer the provider clues for potential sources.
Cobalt chloride (1% Pet) is included on the American Contact Dermatitis Society Standard Series consisting of 80 allergens and cobalt dichloride, 20 mcg/cm2 is on the thin-layer rapid use epicutaneous patch test (site 12).23,24
The Cobalt Spot Test
Although it is rare for the general population to be allergic to cobalt, it is seen in some referred patients with dermatitis. Historically, it has been difficult to discern relevant sources of cobalt exposure (eg, home vs work environment). Identification of the presence of cobalt has become easier with the advent of the chemical detection tool, Cobalt Spot Test Kit (SmartPractice Dermatology, Phoenix, AZ). This kit utilizes the chemistry of 1-nitroso-2-naphthol-3,6-disulfonate and similarly to the dimethylglyoxime test for nickel, it utilizes a color indicator change on exposure to cobalt. 25 The color change is possible due to the main component nitroso-R salt, which has been used in the past to chemically determine multiple metals including cobalt, iron and potassium. The nitroso-R salt causes a complex with cobalt to be formed, which causes oxidation. When in the presence of acetic acid the oxidation reaction changes color, which is responsible for the red color seen in a positive cobalt spot test.26
This test has been shown to be able to detect cobalt released at approximately 8 ppm, which is important because certain patients react to very low levels of cobalt released at approximately 10 ppm. If there remains any doubt about the results of the cobalt spot test, there is also a gel test that can be obtained if necessary, which also will also turn red upon exposure to cobalt. This test may even be more advantageous because it can find cracks in an item where cobalt may be released.25 The cobalt spot test has also been shown to have potential value to react positively to small amounts of cobalt present on a patient’s skin. The researchers stated, however, that suitable test conditions need to be further elaborated.26
Pearls of Treatment: Every Dose Counts
A person might be exposed to and subsequently sensitized to a contact allergen for days to years before demonstrating the clinical picture of ACD. With each exposure, there is an increasing risk of reaching a point at which the immune system meets its metaphorical “threshold” and subsequent exposures at this point can lead to elicitation of a cutaneous response.27 Just as repeated contact over time led to this immune response, repeated avoidance of the majority of exposures over time will induce remission.
Dr. Jacob, the Section Editor of Allergen Focus, is associate clinical professor, dermatology, director of the Contact Dermatitis Clinic at Loma Linda University in Loma Linda, CA.
Dr. Mortensen is currently a dermatology resident at Loma Linda University in Loma Linda, CA.
Disclosure: Dr. Jacob has served as an investigator of Smartchoice USA the PREA-1 and PREA-2 trials.
Disclosure: Dr. Mortensen reports no relavent financial relationships.
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