The Health Gazette
POISON IVY
Summer is here and it is time to spend some quality time outside. Whether you are hiking or working in your garden, you are always at risk for getting poison ivy. There are three types of plants that cause the same itchy red rash. They are poison ivy, poison oak and poison sumac. Poison ivy is by far the most common cause of the allergic skin reaction. The spring and summer are the most common times of the year for poison ivy and oak. Poison ivy and oak have three leaves on each stem and grow as a vine or bush. Sumac has two rows of leaves opposite each other and one leaf at the end of the stem. It grows as a bush or tree. The leaves of all three plants are shiny and coated with an oily chemical, which causes the allergic reaction. The oils are also in the stems and roots of these plants. Pets can get the oil on their furry coats and spread the oil to humans. A particularly severe case of poison ivy can occurs when you are burning debris that contains poison ivy plants. The fire produces a vapor that can be inhaled or deposited on the exposed parts of the skin. The resulting rash can cause a severe reaction that may need more potent medication like a steroid shot or oral prednisone.
ETIOLOGY
All of these plants contain the same oily chemical that causes the rash. It is an allergic contact dermatitis. The chemical is a resin called urushiol. This chemical is nonvolatile and dries quickly on clothing, shoes, animals and tools. Urushiol remains potent for as long as one year. Therefore, it is important to wash any tools, shoes or clothing after exposure to poison ivy. When your skin comes in contact with any part of the plant, it is only a matter of time before you break-out with a rash, assuming you are allergic to it. Not everyone is sensitive to poison ivy. It has been estimated that 70 percent of the population is susceptible to poison ivy. Dark-skinned individuals seem less susceptible than others. Elderly individuals and infants are not as susceptible to the plant but they can still get it. Children become susceptible by age 3 and are highly susceptible by age 12. If you know you have been exposed to poison ivy, it is important to wash off immediately. The resin is absorbed quickly into the skin. As little as ten minutes of exposure may produce the allergic reaction. The eruption is characterized by redness, papules, vesicles and linear streaking. The eruption usually appears within two days but may occur within eight hours. The eruption rarely is delayed longer than ten days. After washing off with soap and water, all of the damage is done. Contrary to popular belief, the fluid in the vesicles or blisters will not spread the rash. This fluid is totally harmless and in no way can spread the rash or make it worse. It is easy to see how this misconception got started. The rash will frequently break out in stages depending on the length of exposure and the amount of urushiol on the skin. If the face is exposed heavily and for a long period of time, then you may break out within 24 hours. If your arms are exposed for one hour, then you may not break out for 48 hours. If your legs are only exposed for ten minutes, then you may not break out for a week. Obviously, it appears as if the rash is spreading over the body. Another factor to consider is the possibility of re-exposure. As mentioned above, the resin will remain on the exposed objects. If you put on your exposed shoes a week later, you can wipe the resin from your shoes on your face or other areas. One of the most severe reactions that I have seen, occurred when a patient was downwind of a neighbor who was burning poison ivy. The urushiol can be vaporized when exposed to a fire. The unfortunate individual who is downwind, could receive a coat of urushiol on any uncovered areas resulting in a surprise case of poison ivy.
TREATMENT
Treatment will depend on how severe the reaction is. For minor cases it may only be necessary to apply an over the counter hydrocortisone cream and some Calamine lotion. For more severe reactions it may be necessary to take an oral steroid such as prednisone. Occasionally, it is necessary to give a shot of a steroid. Benadryl capsules are over the counter and help control the itching. Atarax and Periactin are also excellent, but they require a prescription. Domeboro solution can be very soothing and decrease the itching. Avoid using topical preparations that contain benzocaine, zirconium, or antihistamines. These substances will frequently cause an allergic skin reaction which may worsen the poison ivy.
PREVENTION
The best prophylaxis for allergic contact dermatitis is complete avoidance of the plants. Individuals should learn to recognize and avoid poison ivy. Unfortunately, barrier creams or other solutions are of no value in preventing poison ivy. Long-sleeved shirts and long pants are advisable when working around poison ivy. Occasionally, people cannot avoid poison ivy because of the nature of their job. Some allergists will attempt to desensitize a patient to poison ivy. Unfortunately, this is not always effective.
REFERENCES
Fisher A. Poison Sumac (Anacardiaceae) Rhus Family. Contact Dermatitis 3rd ed. pp. 405-417.
The information provided above is offered as a community service about health-care issues and is not a substitute for individual consultation. Advice on individual problems should be obtained from your personal physician. This information is based on research by the author and represents his interpretation of the literature.
How Poisoning Occurs
Poison ivy, western poison oak, and poison sumac have the poisonous sap in their roots, stems, leaves and fruit. The sap is released
when the plant is bruised, making it easier to contract Rhus-dermatitis in the spring and early summer when leaves are tender. The sap
may be deposited on the skin by direct contact with the plant or by contact with contaminated objects, such as shoes, clothing, tools and
animals. Severe cases have occurred from sap-coated soot in the smoke of burning plants.
The three plants contain a poisonous sap with four antigenic compounds (catechols). The sap is present in roots, stems, leaves, and
fruit. The only parts without the poison are the anthers, pollen, xylem, and epidermis. The poisonous sap is released only after the
epidermis of plants is ruptured. Although the dermatitic capacity of the sap varies little from plant to plant or at different times of the year,
it is easiest to contract Rhus-dermatitis in the spring and early summer, when leaves are tender and bruise easily. The interval between
contact and the appearance of the dermatitis varies considerably, because of the different susceptibilities of individuals and the amount of
poisonous liquid contacting the skin. Most people develop Rhus-dermatitis 24-48 hours after contact. Healing time varies from a few days
to several weeks, and healed sites often remain supersensitive to any further contact with sap for several months.
Under hot, humid conditions the poisonous sap becomes inert in about a week. However, under dry conditions, the plant can retain
its harmful effect for a long period of time. Clothing can be decontaminated by laundering it in a washing machine with soap or detergent.
Infected skin can never be washed soon enough to prevent some dermatitis in sensitive individuals, but washing is useful because it
minimizes the severity of the rash and also prevents the spread of the sap to uninfected parts of the body.
The sap must penetrate the skin before poisoning results; therefore, the most severe poisoning affects areas with thin skin. Symptoms
are less severe or do not occur at all in areas with thick skin or heavy hair.
Clinical evidence shows that no person is completely immune to the poisonous sap. Some are sensitive to small amounts of the
poison, whereas others react only to large amounts. Severe cases of Rhus-poisoning have occurred after supposedly immune individuals
have purposely rubbed Rhus leaves onto their skin. To date, there is no acceptable method of immunization.
Of the three poisonous Rhus species, usually only poison ivy grows in locations that warrant its eradication.
You can destroy poison ivy by cultivation. A single treatment seldom kills the plant completely, as it consists of a vast interconnected
network of above- and below-ground horizontal rhizomes and above-ground vertical stems. Treat the area again as soon as regrowth
occurs from any living parts. Repeated cultivation will eliminate poison ivy because it does not easily regenerate from plant fragments.
Chemicals are recommended for eradication in areas that do not permit cultivation and where some damage to other vegetation can
be tolerated. You can buy a wide range of suitable chemicals at stores that sell pesticides. You may also obtain the latest
recommendations for chemical control from your local agricultural representative or provincial ministry of agriculture.
CAUTION: Be very careful when eradicating these plants. Your boots, protective clothing and implements may pick up the sap and
transfer it to your skin. Do not burn the plants except under controlled conditions, as the sap-covered soot in the smoke will carry the
poison. Also, dead poison ivy plants can still cause dermatitis and must be handled with care.
Poison Ivy, Sumac, and Oak
What is poison ivy, sumac, or oak?
"Poisoning" from plants such as poison ivy, sumac, and oak is an allergic reaction that results when the skin touches these
plants and their oils. Most people develop a rash, blisters, and itching after contact with them. Cases usually occur in the
spring and summer.
Poison ivy and oak have three leaves on each stem and grow as a vine or bush. Sumac has two rows of leaves opposite each
other and one leaf at the end of the stem. It grows as a bush or tree. The leaves of all three plants are shiny and coated with an
oily chemical, which causes the allergic reaction. The oils are also in the stems and roots of these plants.
How does it occur?
The reaction occurs after touching poison ivy, sumac, or oak. A reaction can also occur after contact with anything else that
may carry the plant's oils, including ashes and smoke from burning plants. It can also be spread by touching oil left on clothes
or tools. The rash often appears on the face first and then on other exposed areas of the body. Typically it is first noticed 24 to
48 hours after contact. How bad the rash will be depends on the thickness of your skin and how much contact you had with
the plant's oils.
Sometimes there is a delayed reaction, and the rash develops on one area of your skin after the others. The rash cannot be
spread by scratching itchy skin or from oozing blisters. However, scratching may lead to infection of the open sores.
What are the symptoms?
The symptoms of an allergic reaction to poison ivy, sumac, or oak include the following, from least serious to most serious:
itching, often intense
red blotches that can be either raised or flat
blisters, which may show up in lines
fever
headache
swelling of your throat and eyes
overall swelling of your body
general feeling of discomfort
stomach cramps, nausea, vomiting, diarrhea.
How is it diagnosed?
Diagnosis is based on your having the symptoms listed above and on a physical exam by your doctor.
How is it treated?
To treat poison ivy, sumac, or oak, follow these steps:
Remove your clothes and shoes and wash them in detergent and hot water.
As soon as possible, wash all exposed skin with strong soap and water (or just water) to remove the plant's oils.
Apply cloths soaked in aluminum acetate solution (Burow's solution), then calamine lotion or ointment to reduce the
redness, ease the itching, and help dry up the blisters. Or take lukewarm baths with cornstarch (1/2 cup) or colloidal
oatmeal added to ease the itching. DO NOT use topical antihistamines.
Cover any oozing blisters with a clean gauze bandage soaked in a baking soda and water solution.
If the rash spreads to your face, mouth, eyes, or genitals, or if you develop a fever, headache, extreme redness, pus, or other
severe symptoms, see your doctor. He or she will recommend one or more of the following:
injecting a corticosteroid (powerful anti-inflammatory drugs, such as cortisone, used in treating allergies)
applying corticosteroid ointment or cream to the affected areas two to three times a day, gradually reducing to once a
day
taking oral corticosteroids such as prednisone
taking oral antibiotics or using an antibiotic cream if an infection develops.
Because these are all potent drugs, ask your doctor about any possible side effects or interactions with other drugs you may
be taking.
How long will the effects last?
In most people, the condition clears up in 2 to 3 weeks.
How can I take care of myself?
Follow the steps outlined above to treat your rash. In addition, keep the affected skin clean and dry. Keep your fingernails
well trimmed and clean. Try not to scratch your skin to avoid an infection.
See your doctor if you develop severe symptoms.
What can be done to help prevent a reaction to poison ivy, sumac, or oak?
Follow these guidelines:
Know what the plants look like and where they grow so you can avoid them.
Wear long-sleeved shirts and long pants if you are going to be in an area where these plants grow.
Within 5 to 10 minutes of contact with the plant, rinse exposed skin thoroughly with soap and water (or just water).
Be sure to clean under your fingernails.
Wash clothes and shoes in hot water and detergent to remove any oil that may be on them.
Give any outdoor pets a bath if you think they have had contact with the plants.
Allergic contact dermatitis may account for as many as 20% of all cases of dermatitis in children. Poison ivy, nickel (jewelry),
rubber (shoe dermatitis), balsam of Peru (hand and face dermatitis), formaldehyde (cosmetics and shampoos), and neomycin
(topical antibiotic ointments) are the most common allergens. [4]
RHUS DERMATITIS
In the United States, poison ivy, poison oak, and poison sumac produce more cases of allergic contact dermatitis than all
other contactants combined. The allergens responsible for poison ivy and poison oak allergic contact dermatitis are contained
within the resinous sap material termed urushiol. Urushiol is composed of a mixture of catechols. All parts of the plant contain
the sap. These plants belong to the Anacardiaceae family and the genus Rhus. Other plants in that family, such as cashew
trees, mango trees, Japanese laquer trees, and ginkgo contain allergens identical or related to those in poison ivy. Thousands
of workers on cashew nut farms in India develop hand dermatitis from direct contact with the irritating resinous oil from
cashew nut shells. [5]
Poison ivy and poison oak are neither ivy nor oak species.
Clinical presentation.
Rhus dermatitis occurs from contact with the leaf or internal parts of the stem or root and can
Figure 4-6 Poison ivy. A classic presentation with vesicles and blisters. A line of vesicles (linear lesions) caused by
dragging the resin over the surface of the skin with the scratching finger is a highly characteristic sign of plant contact
dermatitis.
be acquired from roots or stems in the fall and winter. The clinical presentation varies with the quantity of oleoresin that
contacts the skin, the pattern in which contact was made, individual susceptibility, and regional variations in cutaneous
reactivity. Small quantities of oleoresin produce only erythema, whereas large quantities cause intense vesiculation (Figures 4-6
and 4-7) .
The highly characteristic linear lesions are created when part of the plant is drawn across the skin or from streaking the
oleoresin while scratching. Diffuse or unusual patterns of inflammation occur when the oleoresin is acquired from contaminated
animal hair or clothing or from smoke while burning the plant. The eruption may appear as quickly as 8 hours after contact or
may be delayed for a week or more. The appearance of new lesions a week after contact may be confusing to the patient,
who may attribute new lesions to the spread of the disease by touching active lesions or to contamination with blister fluid.
Blister fluid does not contain the oleoresin and, contrary to popular belief, cannot spread the inflammation.
Treatment of inflammation.
Washing the skin with any type of soap inactivates and removes all surface oleoresin,
Figure 4-7 Poison ivy dermatitis. Diffuse erythema with vesicles over the entire surface.
87
thereby preventing further contamination. Washing is most effective if done within 15 minutes of exposure.
Blisters and intense erythema.
Cold wet compresses are highly effective during the acute blistering stage. They should be used for 15 to 30 minutes several
times a day for 1 to 3 days until blistering and severe itching is controlled. Topical steroids do not penetrate through blisters.
Prednisone, administered in a dosage of 20 mg twice each day for at least 6 days, is used for severe, widespread
inflammation. Patients who may have trouble adhering to a medication schedule may be treated with triamcinolone acetonide
(Kenalog, Aristocort; 40 mg suspension) given intramuscularly. Commercially available steroid dose packs should be avoided;
they provide an inadequate amount of medicine. Patients who do not initially seem to require medication may become much
worse 1 or 2 days after an office visit; they should be advised that prednisone is available if their conditions worsen.
Short, cool tub baths with or without colloidal oatmeal (Aveeno) are very soothing and help to control widespread acute
inflammation. Calamine lotion controls itching but prolonged use causes excessive drying. Hydroxyzine and diphenhydramine
control itching and encourage sleep.
Mild to moderate erythema.
Topical steroid gels or creams (groups III through V) applied 2 to 4 times a day rapidly suppress erythema and itching.
Prophylactic treatment.
Complete desensitization cannot be accomplished. Poison ivy oleoresin in capsules and injectable syringes for
hyposensitization has been removed from the market by the FDA.
Contact Dermatitis.
Contact dermatitis is an inflammatory reaction of the skin to a chemical, physical, or biologic agent. The inducing agent acts as
an irritant or allergic sensitizer. Allergic contact dermatitis is a form of delayed hypersensitivity mediated by lymphocytes
sensitized by the contact of the allergen to the skin. It is less common than irritant contact dermatitis. [70] Caustics, industrial
solvents, and detergents are common causes of irritant dermatitis. Dermatitis may result from a brief contact with a potent
caustic or from repeated or prolonged contact with milder irritants.
Clothing, jewelry, soaps, cosmetics, plants, and medications contain allergens that commonly cause allergic contact dermatitis.
The most common allergens include rubber compounds, plants of the Rhus genus (poison ivy, oak, and sumac), nickel (often
used in jewelry alloys), paraphenyldenediamine (an ingredient in hair dyes and industrial chemicals), and ethylenediamine (a
stabilizer in topical medications). [71] Sensitization to poison ivy results in sensitization to other plants in this family such as
cashew, mango, lacquer, and ginkgo trees. [71]
The primary lesions of contact dermatitis are papules, vesicles, or bullae on an erythematous bed. Of the allergens, Rhus
species are the most likely to cause bullous eruptions. Oozing, crusting, scaling, and fissuring may be found, along with
lichenification in chronic lesions. The distribution of the eruption depends on the specific contactant and may be localized,
asymmetric linear, or unilateral (Figs. 164-12 (Figure Not Available) and 164-13) (Figure Not Available) . Mucous
membranes are usually spared unless directly exposed to the inciting agent. A history of exposure is the most significant factor
favoring the diagnosis. If doubt exists about the diagnosis, the patient should be referred for allergic patch testing.
Figure 164-12 (Figure Not Available) Contact dermatitis secondary to nickel. (Photo by David Effron, MD.)
Figure 164-13 (Figure Not Available) Typical linear lesions of contact dermatitis secondary to poison ivy. (Photo by David Effron, MD.)
The treatment includes avoidance of the irritant or allergen and treatment of secondary bacterial infection. Oozing or
vesiculated lesions should be treated with cool wet compresses of Burow's solution applied for 15 minutes 3 or 4 times daily.
Topical corticosteroid creams or ointments help reduce inflammation and pruritus. A short course of systemic corticosteroids
is necessary. [72] Prednisone in a dosage of 30 to 80 mg/day (depending on the severity of involvement) should be prescribed
initially. This should be tapered over 10 to 14 days with the dosage decreased by 10 mg each day until a dose of 40 mg is
reached. It should then be decreased in daily increments of 5 mg. The treatment may be discontinued without further tapering
when a daily dose of 10 mg is reached. The medication is best taken as a single morning dose. Systemic antihistamines, such
as hydroxyzine or diphenhydramine, may help control pruritus. [71]
Diaper Dermatitis.
Diaper dermatitis is a common disorder. The condition is exacerbated by heat, moisture, friction, and the presence of urine
and fecal material. Occlusive clothing in infants tends to foster all of these. Lesions begin
P2791
Figure 164-14 (Figure Not Available) Erythema multiforme. (Photo by David Effron, MD.)
as erythematous plaques in the genital, perianal, gluteal, and inguinal areas. More severe involvement results in moist, eroded
lesions that may extend beyond the primary areas of appearance.
Infection with C. albicans and fecal bacterial flora is an important contributory factor to the development of diaper dermatitis.
Lesions infected with Candida are moist, red patches with well-demarcated borders. Papular or pustular satellite lesions are
also present.
Diaper dermatitis may reflect the presence of atopic or seborrheic dermatitis in the infant. The presence of lesions elsewhere
on the body, particularly on the face, in cases of atopic dermatitis, or the scalp, in cases of seborrhea, alert the physician to
these possibilities. Ammonia and bacterially produced putrefactive enzymes produce dermatitis as contact irritants. Such
rashes are accompanied by characteristic odors. The existence of diaper dermatitis as a true allergic contact dermatitis is rare.
Treatment consists primarily of altering the physical environment in which diaper dermatitis thrives. Excess clothing should be
removed, and occlusive plastic or rubber diaper covers should not be used. Diapers should be changed frequently and left off
for prolonged periods if possible. Sterilized cloth diapers are preferred.
If exudative lesions are present, treatment with topical cool wet compresses of saline or Burow's solution is indicated for 2 to
3 days. Continuous air exposure of the area should be attempted. [71] Zinc oxide (Desitin) may dry the area. Severe contact or
seborrheic dermatitis may require short-term treatment with topical corticosteroids, such as 1% hydrocortisone in a cream
base. [73] Ointment-based topical medications for treatment of diaper dermatitis should be avoided because their occlusive
nature enhances moisture retention. Nystatin cream or powder should be applied to lesions infected with Candida.
Journal of Allergy and Clinical Immunology
Volume 105 • Number 3 • March 2000
Copyright © 2000 Mosby, Inc.
Current reviews of allergy and clinical
The diagnostic evaluation, treatment, and prevention of allergic contact dermatitis in the new
millennium
Donald V. Belsito MD
Key words
Allergic contact dermatitis
common allergens
clinical manifestations
diagnostic evaluation
immunoregulation
treatment
prevention
From the Division of Dermatology, University of Kansas Medical Center, Kansas City, Kan.
Received for publication Dec 7, 1999.
Accepted for publication Dec 9, 1999.
Reprints not available from the author.
Copyright © 2000 by Mosby, Inc.
0091-6749/2000 $12.00 + 0 1/1/104937
Kansas City, Kan
Identifying the etiology of allergic contact dermatitis is a rewarding yet challenging endeavor. Not all allergic
contact reactions are eczematous in appearance. The most reliable clinical clue to the allergic nature of the
dermatitis is its geographic distribution. Once a list of culprit allergens has been identified by patch testing, the
practitioner must identify the relevant allergen(s) and counsel the patient in avoidance. For most individuals,
allergen avoidance results in resolution of the dermatitis; however, some patients will require continuing
symptomatic therapy despite avoidance. For those patients unable to avoid known allergens, immunosuppressant
therapies (including phototherapy) or barriers can be beneficial. Currently, hyposensitization is not a viable
alternative for the treatment of allergic contact dermatitis. (J Allergy Clin Immunol 2000;105:409-20.)
Abbreviations used
ACD:
Allergic contact dermatitis
DMDM:
Dimethyoldimethyl
GPT:
Guinea pig tests
ICCVAM:
Interagency Coordinating Committee on the Validation of Alternative Methods
LCs:
Langerhans cells
LLNA:
Local lymph node assay
MCI/M:
Methylchloroisothiazolinone/methylisothiazolinone
NACDG:
North American Contact Dermatitis Group
PPD:
para-Phenylenediamine
PUVA:
Psoralens ultraviolet radiation
ROAT:
Repeat open application testing
TAP 2B:
Transporter associated with antigen processing 2B
UVB:
Ultraviolet B radiation
Contact dermatitis can be either allergic or irritant in etiology. The diagnosis is not usually apparent from history or physical
examination alone. Without patch testing, it is impossible to delineate the cause. Thus, although it has been 105 years since
Jadassohn[1] first described the use of patch tests, such testing remains vital to the appropriate diagnosis of contact dermatitis.
Indeed, perhaps the only suspected allergic condition where patch testing is not indicated is that induced by exposure to plants
of the Toxicodendron species, which can usually be recognized by the presence of the intense, often linear, papulovesicular
eruption they induce (Fig 1).
(Figure Not Available) Fig. 1. Acute dermatitis caused by poison ivy. Note linear arrangement of lesions typical of phytodermatitis acquired by
inadvertent contact with the plant. The severe vesiculobullous reaction is typical for urushiol, the pentadecylcatechol of Toxicodendron spp.
(Reproduced with permission of the Ronald O. Perelman Department of Dermatology, New York University School of Medicine.)
For most other suspected allergic reactions, patch testing is indicated and can be quite illuminating.[2] For example, it has been
reported that 46% of patients who are seen with a history of apparent metal-induced dermatitis are patch test negative to
nickel.[3]
Although allergic contact dermatitis (ACD) can occur in any setting, many cases are related to exposures in the workplace.
When all occupationally related illness in the United States was last estimated, ACD accounted for 7%, at an annual cost of
$250 million in lost productivity, medical care, and disability payments.[4] Although the disease has probably plagued humans
for millennia, the term allergy[5] and its clinical recognition by patch testing[1] are barely a century old. With the advent of an
experimental animal model for ACD in 1926,[6] studies concerning its pathophysiologic features became possible. Despite all
the clinical and scientific research since, a thorough understanding of the disease remains elusive.
THE ALLERGENS
Most environmental allergens are haptens, that is, simple chemicals that must link to proteins to form a complete antigen before
they can sensitize. [7] These haptens are primarily small (<500 d) electrophilic molecules that bind to carrier proteins by
covalent bonds [8] (Table I).
Table I. Thirty of the most frequent allergens in the United States, 1996 to 1998*
Allergen
No. of patients tested
Positive reactions (%)
Reactions considered
currently relevant (%)
Nickel sulfate
3429
14.2
49.1
Neomycin sulfate
3436
13.1
46.2
Balsam of Peru (Myroxylon
pereirae)
3439
11.8
82.9
Fragrance mix
4095
11.7
86.9
Thimerosal
4087
10.9
16.8
Sodium gold thiosulfate
4101
9.5
40.6
Formaldehyde
3440
9.3
63.2
Quaternium-15
3436
9.0
88.7
Cobalt chloride
4095
9.0
55.1
Bacitracin
4103
8.7
50.4
Methyldibromo
glutaronitrile/phenoxyethanol
4054
7.6
59.1
Carba mix§
3437
7.3
71.7
Ethyleneurea
melamine-formaldehyde resin
4095
7.2
65.9
Thiuram mix
3435
6.9
79.8
p-Phenylenediamine
3441
6.0
53.1
Propylene glycol
4095
3.8
82.8
Diazolidinyl urea
4096
3.7
91.5
Lanolin
3442
3.3
78.9
Imidazolidinyl urea
4094
3.2
91.7
2-Bromo-2-nitropropane-1,3-diol
4094
3.2
68.5
MCI/MI
4083
2.9
87.2
Cinnamic aldehyde
3443
2.8
83.2
Potassium dichromate
3440
2.8
54.3
Ethylenediamine dihydrochloride
3439
2.6
23.9
DMDM hydantoin
4093
2.6
93.4
Glutaraldehyde
4094
2.6
48.1
Tixocortol-21-pivalate
4100
2.3
91.7
Benzocaine
3444
2.0
34.3
Colophony
3443
2.0
36.2
Epoxy resin
3439
1.9
55.2
Data from Marks et al. [9] MCI/MI, Methylchloroisothiazolinone/methylisothiazolinone; DMDM, dimethyoldimethyl.
*The population studied consisted of patients with suspected ACD referred for patch testing and is therefore not necessarily
representative of the general population.
Although Toxicodendron oleoresin in poison ivy/oak is a frequent cause of ACD, it is not listed because it was not
tested in this study.
Cinnamic alcohol 1%, cinnamic aldehyde 1%, hydroxycitronellal 1%, amylcinnamaldehyde 1%, geraniol 1%, eugenol
1%, isoeugenol 1%, oakmoss absolute 1%.
§1,3-Diphenylguanidine 1%, zinc diethylthiocarbamate 1%, zinc dibutyl-dithiocarbamate 1%.
Tetramethylthiuram disulfide 0.25%, tetramethylthiuram monosulfide 0.25%, tetraethylthiuram disulfide 0.25%,
dipentamethylenethiuram disulfide 0.25%.
The major exception to such covalent bonding occurs among the metallic salts (for example, nickel and cobalt), which are
thought to complex with proteins in a manner analogous to the complexing of cobalt with vitamin B12 . Although there are more
than 2800 known environmental allergens,[10] not all electrophilic, protein-binding substances are haptens.[11] The nature of the
antigenic determinants, the type of binding that the hapten undergoes with the carrier, the final 3-dimensional configuration of
the conjugate, and a variety of unknown factors undoubtedly contribute to the antigenicity of a chemical.[12] However, the
importance of the carrier for the hapten cannot be underestimated because potent contact sensitizers, when complexed to
nonimmunogenic carriers, induce tolerance rather than sensitization.[13] HLA-DR or class II antigens on the surface of the
antigen-presenting Langerhans cells (LCs) act as the binding site (carrier) for contact allergens.[14] Readers interested in
current reviews of the pathophysiologic mechanisms of ACD are referred elsewhere.[15] [16]
IMMUNOREGULATION
Although animal studies have clearly shown genetic restrictions on cell-mediated immunity, the evidence for a genetic influence
in humans has been minimal. Skog[17] found that 5% of a defined population could not be sensitized to dinitrochlorobenzene
and suggested that this was due to inheritance. In another study significant genetic association with the capacity to become
sensitized to para-nitrosodimethylaniline was reported.[18] Nonetheless, attempts to correlate HLA haplotype with nickel
sensitivity[19] or other contact allergies[20] have shown no association. However, recent studies have demonstrated increased
allele and phenotype frequencies of "transporter associated with antigen processing" 2B (TAP 2B) genes in nickel-sensitive
subjects.[21] Thus definitive evidence of genetic influences on ACD in humans has been meager, probably because of our
diverse genetic pool and the current limitations of technology. [22] With continuing advances in molecular biology, any
association(s) should become clearer in the future.
The route of primary sensitization clearly has a regulatory effect on the subsequent immunologic response. Sulzberger[23]
demonstrated that intracardiac injection of neoarsphenamine induced tolerance rather than sensitization. Tolerance induction
has also been reported after primary oral ingestion of allergens[24] and after primary epicutaneous application of allergens to
areas deficient in HLA-DR+ LCs.[25] The exact mechanism by which tolerance ensues is controversial and may depend on the
route of exposure (oral, intravenous, epicutaneous, or intraperitoneal). However, in most instances induction of hapten-specific
suppressor T cells,[25] clonal deletion of the responding CD3-Ti cells,[26] or antibodies directed against the antigen recognition
site of the T-cell receptor (anti-idiotypic antibodies)[27] seem to play a role. Readers interested in a better understanding of the
mechanism(s) of tolerance induction are referred elsewhere.[26] [28]
The aging process also modulates ACD. Clinically, aged individuals have been shown to have various defects in the induction
or elicitation of ACD.[29] The precise reason for this decline in contact sensitivity is unknown, but it is likely multifactorial.
Various portions of the cell-mediated response pathway are involved, including decreases in the density of antigen-presenting
cells and in the production of proinflammatory cytokines.[30] Experiments in which contact-sensitized aged mice were injected
with naive young T cells and subsequently demonstrated normal responses on antigenic challenge suggest that a failure of
T-cell amplification signals or the generation of sufficient T effector cells may be the major deficiencies in aged animals.[31]
The age at which immunocompetency is fully established in infants and children remains controversial.[29] In the past it was
believed that ACD rarely developed in children because of an immature immune system and that patch testing of children with
standard concentrations of allergens resulted in a high percentage of irritant reactions.[32] However, recent data suggest that
patch testing of children with the allergens commercially available in the United States does not result in increased, and
confounding, irritant responses.[33] Nonetheless, documented allergic reactions are seen mostly in older pediatric patients and
are the result of topical medications, plants, nickel, or shoe-related allergens.[34] As suggested by Strauss,[35] who was able to
sensitize 35 of 48 infants (1 to 4 days old) to Toxicodendron oleoresin, the apparent hyporesponsiveness of children may be
due to limited exposure and not to deficient immunity. Similarly, the effects of gender on the incidence of ACD seem related to
the likelihood of exposure.[29] [36]
Impairment of cell-mediated immunity has been reported in certain diseases. In addition to the obvious disorders associated
with immunologic deficiency, such as AIDS or severe combined immunodeficiency, diseases as diverse as lymphoma,
sarcoidosis, atopic dermatitis, lepromatous leprosy, and destructive conglobate acne have been associated with diminished
reactivity or anergy.[37]
In experimental models down-regulation of ACD has consistently been achieved with ultraviolet radiation (ultraviolet B [UVB]
or psoralens ultraviolet [PUVA]), glucocorticosteroids, and cyclosporine.[38] A variety of other pharmacologic agents have
been reported to interfere with the induction or elicitation of ACD in mouse models.[2] These include calcium-channel
blockers, amiloride, pentoxifylline, pentamidine, clonidine, spiperone, N-acetylcysteine, and flavonoids. Of these, only
pentoxifylline has been evaluated in humans, where it was found to induce a slight reduction in responsiveness, [39] perhaps by
an effect on TNF-alpha. Whether the other pharmacologic agents exert any effect on the human response remains to be
determined. Of note, histamine H1 receptor antagonists do not appear to modulate the induction or elicitation of ACD,
whereas H2 receptor antagonists enhance the induction, but not the elicitation, phase.[2] [40]
CLINICAL MANIFESTATIONS
The clinical appearance of ACD varies depending on its location and duration. Acute eruptions are typically characterized by
macular erythema and papules, vesicles, or bullae, depending on the intensity of the allergic response (Fig 1). However, in
acute ACD in certain areas of the body (eyelids, penis, and scrotum) erythema and edema predominate, whereas vesiculation
is rare. In contrast, chronic ACD of most cutaneous sites presents as a lichenified, scaling, or fissured dermatitis, with or
without accompanying papulovesiculation (Fig 2, A and B).
Fig. 2. Chronic dermatitis of (A) eyelids and (B) neck, but not hands, from allergen in nail care products. The patient was
allergic to tosylamide formaldehyde resin in her nail polish. Similar reactions from cyanoacrylate-containing nail glue and
other acrylate products used about the nails can be observed. The absence of an associated dermatitis of the fingers or hands
is not unusual. (Reproduced with permission of the Ronald O. Perelman Department of Dermatology, New York University
School of Medicine.)
Thus neither the morphologic nor the histopathologic characteristics of ACD are necessarily distinctive. The clinicopathologic
differential diagnoses include irritant contact, atopic, nummular, seborrheic, dyshidrotic, psoriasiform (especially on palms and
soles), and autosensitization dermatitis.
ACD initially involves the cutaneous site of principal exposure. As it evolves, it may spread to other more distant sites either
by inadvertent contact or, under certain circumstances, by autosensitization. Furthermore, the scalp, palms, and soles are
relatively resistant to ACD and may exhibit few pathologic features despite contact with an allergen that produces significant
dermatitis in adjacent areas of the skin.
Although the failure of an eczematous dermatitis to respond to standard treatments may suggest the possibility of ACD, the
shape(s) and location(s) of the rash provide the most important clues, especially as to the causal allergen.[41] ACD to plants
(eg, poison ivy, poison oak, Primula obconica, and English ivy) is often characterized by linear lesions (Fig 1).
Aeroallergens such as the sesquiterpene lactones in Compositae involve the more exposed areas of skin with relative sparing
of clothed areas. In contrast, textile-related allergens produce dermatitis of clothed areas (Fig 3).
Fig. 3. Acute contact dermatitis of upper arms caused by allergic reaction to disperse blue dyes. Reactions to textile dyes, as
opposed to resins, may take on a highly patterned form, as demonstrated here. Unfortunately, most cases of ACD are not this
graphic. (Reproduced with permission of the Division of Dermatology, University of Kansas Medical Center.)
Not all allergic reactions are necessarily eczematous. For example, I recently evaluated a young man who had a recurrent
papular eruption of the bathing suit area, which was diagnosed as "sea bather's eruption" because of the larvae of the sea
anemone, Edwardsiella lineata. It was only when the dermatitis recurred after swimming in a pool that another cause was
suspected. Patch testing revealed that he was allergic to the dyes in his bathing suit and his rash cleared when he changed to
another-color suit. Noneczematous appearing variants of ACD include lichenoid contact,[42] [57] the cellulitic-like appearance
of dermal contact hypersensitivity,[58] contact leukoderma,[59] contact purpura,[60] erythema dyschromicum perstans,[61] and
erythema multiforme, [62] among others. Of these, the lichenoid variants are most likely to be seen clinically because they have
been noted to be a reaction pattern for a number of allergens, including dental amalgams[42] [44] (eg, mercury, palladium, silver,
and gold), tattoo pigments,[45] [47] (eg, mercury, cobalt, and chromium), other metals[48] (nickel), para-phenylenediamine[49]
(PPD) and its derivatives[50] (eg, the substituted PPD's used as antioxidants in black rubber), photographic color developers[51]
(eg, CD-2 and CD-3, Fig 4), flavoring agents[52] (menthol and peppermint), Red Sea coral,[53] aminoglycoside antibiotics,[54]
alpha-amylase,[55] fragrances [56] (especially photoallergy to musk ambrette), and plants[57] (especially Primula spp).
Fig. 4. Lichenoid contact dermatitis caused by exposure to the photographic color developers CD-2 and CD-3. The classic
lichenoid papules can be seen against a background of lichen simplex chronicus induced by chronic scratching. A number of
other allergens (see text) can induce such lichenoid responses. (Reproduced with permission of the Division of Dermatology,
University of Kansas Medical Center.)
In addition, many drugs may cause a lichenoid hypersensitivity, the most notorious being the quinine derivatives,[63]
hydroxyurea, [64] angiotensin-converting enzyme inhibitors,[65] beta-blockers, [66] and antiepileptic agents.[67]
A GEOGRAPHIC APPROACH TO IDENTIFYING ALLERGENS
As stressed by Cohen and Brancaccio,[68] a careful clinical assessment of the patient is required before any diagnostic tests to
correctly identify causal allergens. Recently Krasteva et al[69] have published on the most frequently encountered causes of
ACD in the major anatomic areas of the body. Summarized below is my approach to regional contact dermatitis.
ACD of the face, ears, and neck can present particular difficulties in determining the causative allergen because many
substances could be responsible. The work environment must be examined in detail for potential clues: common work-related
materials causing facial ACD include respirators, masks, aerosolized mists (such as those encountered by machinists), and
volatile organic substances (for example, the amine hardeners in the plastic industry). Practitioners must also investigate
nonoccupational exposures: the components of facial cosmetics (vehicles, preservatives, emulsifiers, fragrances), sunscreens
(and other photoallergens), and grooming aids (eg, eyelash curlers [nickel, rubber] or makeup applicators [rubber]). In
addition, allergy to chemicals applied to the scalp, which has a greater resistance to ACD, may manifest itself on the face,
ears, and neck while sparing the scalp (eg, ACD from PPD in hair dyes or glyceryl thioglycolate in hair permanents).
When a facial dermatitis is particularly severe about the eyelids, the components of ophthalmic medicaments, eyelid/eyelash
cosmetics, or airborne ACD must be considered. In many parts of the United States the most common airborne allergen is
ragweed. However, it is also necessary to be concerned about other materials, such as volatile organic substances, fragrances,
and chemicals contained in smoke. Other causes of a facial dermatitis with accentuation about the eyelids, especially the upper
lids, are products that are applied to the hands and are unwittingly transmitted to the face. In women these chemicals are
frequently found in nail enamels applied to the fingernails. Previously, tosylamide formaldehyde resin was the common culprit
but, today, numerous acrylics are being used in nail polishes and topcoats and are becoming almost as common a cause of
allergic eyelid dermatitis as the formaldehyde resins (Fig 2, A and B).
Although ACD of the neck is often associated with a facial dermatitis, patients can also have an isolated dermatitis of the neck.
In these cases there are 3 groups of chemicals likely to have caused the reaction. Cosmetic allergens, especially fragrances
and nail care chemicals, typically induce dermatitis on the lateral neck. A linearly distributed dermatitis of the lower neck
frequently results from reactions to metals and occasionally to exotic woods, present in necklaces. The third common cause
for a nuchal dermatitis, again one that wraps linearly about the lower part of the neck, is textile dermatitis to either the dyes or
the formaldehyde resins in clothing. Periaxillary involvement sparing the vault of the axillae should lead to the strong suspicion
of allergy to textiles.
Dermatitis overlying the torso is frequently textile related. Typically, textile dermatitis is accentuated about the posterior neck,
upper back, lateral thorax, waistband, and flexor surfaces of the extremities, with relative sparing of the axillary vault and
undergarment areas. The usual textile allergens are the azo-aniline (disperse) dyes used to color clothing and/or the urea
formaldehyde resins used to finish the clothing, especially clothing resistant to wrinkling. Other causes of textile dermatitis
include the rubber-related allergens found in elasticized garments and the metal allergens found in the metallic components of
clothing.
Generalized reactions of the torso and extremities can be due to allergens other than those present in textiles. For example,
patients can react to fragrances, preservatives, vehicles, and other constituents of moisturizing lotions. Although the product
may be applied to the entire body, the rash often takes on a textile-like distribution. Such a reaction pattern points out the role
of such nonimmunologic factors as friction, pressure, heat, and perspiration in accentuating the allergic response.[15]
Dermatitis of the hands and forearms that ends at the midupper arms, particularly when associated with a facial dermatitis,
suggests a photosensitive process. When the face is not involved and when the patient has made no attempt to protect the
facial skin from sun exposure, look for occupational allergens and for potential allergens in soaps and moisturizing creams used
only for the hand and arms.
Isolated hand dermatitis is one of the most challenging problems for physicians. When seeking an allergic cause for hand
dermatitis, pay particular attention to those chemicals listed in standard texts[70] that are handled in the occupation(s) and
hobbies of the patient. In addition, the many household and cosmetic products the patient uses must be identified. In general,
when an allergen is applied to the entire hand, the thinner dorsal skin is more severely involved than the thicker palmar skin,
where the density of antigen-presenting LCs is decreased.[71] Although the palmar aspects of the hands are relatively resistant
to the induction of allergy and typically are less involved than the dorsal aspects, if the patient is handling a solid object that
contacts only the palmar aspects the dermatitis will occur only in this area.
Together with the feet, the popliteal fossa and inner thigh are the most common areas of the lower extremity to be affected by
ACD. The most frequently encountered allergens are those in textiles. In women, dyes in pantyhose (especially blue disperse
dyes in darker-colored hose and disperse yellow No. 3 in flesh-colored hose) are the usual offenders. Other nontextile causes
of ACD of the legs include the fragrances, preservatives, and vehicles present in moisturizers and other cosmetic preparations.
ACD of the feet is seen much less commonly than that of the hands; however, as with the hands, the dermatitis is usually most
severe over the dorsal aspect of the feet. ACD of the feet is often accentuated over the joints and spares the lateral aspects of
the toes and thicker skinned heel area. The allergic nature of this condition is suggested by the sparing of the arch of the foot
and of the creases of the toe. Like the palmar hand, if the plantar foot is the only portion contacting the allergen, the dermatitis
will be restricted to this area. The most common allergens are para-tertiary butylphenol formaldehyde resin (a component of
shoe glues), rubber components, and chromate (used to tan leather). Shoe dyes are very uncommon causes of allergy.[72]
Allergens applied to mucosal surfaces very often do not induce significant mucosal pathologic features. Most patients allergic
to allergens applied intraorally have cheilitis but not stomatitis. The unusual individual who reacts to nickel, mercury, palladium,
or gold in dental amalgams presents with a systemic contact dermatitis, with or without a localized, often lichenoid,
stomatitis.[73] Given the widespread exposure of the oral mucosa to allergens, the limited number of reports of mucosal ACD
makes it obvious that patients rarely react to allergens intraorally. The reason for this is unclear.
It is not unusual for a patient with ACD to have a "scattered, generalized" dermatitis. These reactions are usually the result of
allergens that are ubiquitous in the environment, such as formaldehyde, formaldehyde-releasing preservatives, rubber-related
chemicals, nickel, fragrances, and balsam of Peru. However, individuals can also have a widespread cutaneous eruption after
internal absorption of chemicals to which they were previously sensitized topically.
Although uncommon, reactions to internally absorbed chemicals, referred to as "systemic contact dermatitis," occur in
individuals who have been sensitized topically to an allergen and are subsequently re-exposed systemically. Such re-exposure
can be in the form of a drug or chemical introduced intramuscularly, intravenously, orally, rectally, or vaginally. Other sources
of exposure include foods and medical or dental devices that contact mucosal surfaces or that have been implanted surgically
into the body. Although the clinical reaction is typically a dermatitis limited to the site(s) of the original sensitization, more
pronounced reactions ranging from an extensive, bizarre-appearing dermatitis to erythroderma also occur. Agents such as
cinnamic aldehyde and balsam of Peru (which can be used as flavorings) or parabens (which are common food preservatives)
must be highly suspect in such cases. In addition, contaminants in foodstuffs, such as nickel,[74] [75] can also cause systemic
ACD. Systemic contact dermatitis highlights one of the poorly understood aspects of ACD: the potential for long-lasting
immunologic memory in previously sensitized areas of skin.
Finally, iatrogenic ACD must always be suspected when the primary dermatitis does not respond to usual therapies. A
secondary ACD of the hands can develop in a patient with nonallergic hand dermatitis who uses rubber gloves to protect the
hands. Iatrogenic contact dermatitis can also develop from the various topical preparations, including prescriptions, that
patients apply. In the United States the principal offending allergens are topical antibiotics (neomycin and bacitracin)[76] and
topical glucocorticosteroids.[77] It can be particularly difficult to identify the allergic nature of iatrogenic ACD because the
eczematous quality can be muted by the underlying dermatosis-dermatitis for which the topical preparation was used.
DIAGNOSIS
The only useful and reliable method for the diagnosis of ACD remains the patch test. Only 23 commercially prepared allergens
are currently available in the United States (Table II).
Table II. T.R.U.E. TEST Allergen Patch Test Panel*
Allergens
Principal contactants
Nickel
Metals, foods
Lanolin (wool) alcohol
Vehicle for creams and lotions
Neomycin sulfate
Antibiotics, vaccines
Potassium dichromate
Leather, spackling compounds, detergents
Caine mix
Anesthetics
Fragrance mix
Fragrances, flavorings
Colophony (rosin)
Adhesives, waxes, rosin
Paraben mix
Preservative in creams, lotions, foods
Negative control
Balsam of Peru
Fragrances, flavorings
Ethylenediamine dihydrochloride
Stabilizers in creams, lotions, and intravenous solutions,
certain antihistamines
Cobalt
Metals, blue pigments, vitamin B12
Para-tertiary-butylphenol formaldehyde resin
Adhesives, shoe glues
Epoxy resin
Glues, plastics
Carba mix
Rubber products, fungicides
Black rubber mix
Rubber products
MCI/MI
Preservative in creams and lotions
Quaternium-15
Preservative in creams and lotions
Mercaptobenzothiazole
Rubber products
Para-phenylenediamine
Hair dyes (poor screen for textile dyes)
Formaldehyde
Preservative in many materials
Mercapto mix
Rubber products
Thimerosal
Preservatives in medications and vaccines
Thiuram mix
Rubber products, fungicides
*Manufactured by Kabi Pharmacia Service A/S, Hillerod, Denmark, and marketed in the United States by Glaxo
Dermatology, Research Triangle Park, NC 27709.
A comparison of Table I with Table II makes it apparent that most, but not all, of the common allergens in the environment are
contained on these trays. However, given the fact that there are greater than 2800 potential environmental allergens,[10]
physicians interested in fully evaluating patients with ACD must be prepared to perform tests with other materials. For
individuals compounding their own allergens, texts detailing appropriate concentrations and vehicles are available.[10]
Like any in vivo assay, patch testing is subject to pitfalls.[78] A primary concern is that even when a chemical is found to be
allergenic for a given patient, it cannot be assumed that it is the cause of the dermatitis. As Table I illustrates, the relevance of
presumably true-positive reactions to current episodes of ACD ranges from as low as 16.8% for thimerosal to as high as
93.4% for DMDM hydantoin. To determine whether an allergen is likely to be the culprit, the results of a positive patch test
must always be correlated with materials encountered by involved areas of skin. Furthermore, even when patients are allergic
to chemicals in products they are using, the allergen may be present in only minimal amounts and may not be responsible for
the dermatitis. In this regard, repeat open application testing (ROAT), in which the patient applies the commercial product to
normal skin several times daily for 1 to 2 weeks, can be helpful.[79] With use of such provocative tests, members of the North
American Contact Dermatitis Group (NACDG) found that 5 of 10 individuals who tested positive to MCI/MI at 100 ppm in
water did not react to a generic skin care lotion preserved with 15 ppm MCI/MI. [80]
When performing patch tests, the clinician must always be alert to the possibility of false-positive and false-negative reactions.
False-positive reactions can result from the use of allergens at irritant concentrations or from the excited skin syndrome.[81] The
false nature of these reactions can usually be resolved by repeating the patch tests individually or in lower concentrations. In
contrast, false-negative reactions are more difficult to detect and require high levels of suspicion and diligence to uncover.
One way to avoid false-negative reactions is to perform a second reading of the test sites after the initial 48-hour inspection.
This second reading, sometime between 4 and 7 days after application of the patches, is particularly important for elderly
patients, who take longer to mount an allergic reaction.[82] A second reading is also important in detecting positive reactions to
allergens such as neomycin, more than half of which are not evident until 96 hours after application of the patch test.[83] Geier
et al[84] have identified PPD and cobalt as other allergens that are "slow" to develop. In their exhaustive study of 3475 patients,
it was found that readings at days 3 and 5 after placement of the patch tests yielded the greatest number of positive results.
False-negative reactions can also occur when the allergen is used at too low of a concentration for patch testing, as can
happen when cosmetic products are tested as is. False-negative reactions in these circumstances are a result of threshold and
vehicle phenomena, which are only now being studied. It has been reasoned that both quantitative (eg, the degree to which
hapten is conjugated and the intensity of signals for LC migration and maturation) and qualitative (eg, the type of immune
response elicited) factors are involved in false-negative reactions.[85] In this regard, it has been shown that sensitization (and
presumably elicitation) is dependent on the dose of chemical per unit area of skin, as opposed to the total dose delivered,
down to a limit of <0.1 cm2 of skin.[86] Rees et al[87] reported that when an allergen was applied to an area of 0.08 cm2 , little
sensitization ensued, suggesting that a minimal number of epidermal LCs must be activated to elicit a response. In addition, the
vehicle for the chemical can have a significant impact on the response by affecting such processes as skin penetration, cytokine
production, LC migration, and other variables.[88] [90] Therefore, if clinical suspicion warrants, and despite a negative patch
test, additional testing such as ROAT with the suspect product can unmask the cause of ACD.
With more than 2800 potential allergens,[10] negative reactions may simply indicate that the responsible chemical has not been
tested. Although it has been widely quoted that 70% to 80% of patients with ACD can be diagnosed with use of screening
trays such as the T.R.U.E. TEST (Kabi Pharmacia Service A/S, Hillerod, Denmark),[91] these numbers have recently been
questioned. In an analysis of the 1994-1996 NACDG data on 3120 patients,[92] it was found that 62% of these individuals
had at least one positive reaction to an allergen present on the T.R.U.E. TEST, of which 45% were relevant to the current
dermatitis. However, by expanding the panel from 23 to 50 allergens, additional allergens of potential relevance were
identified in 31% of these patients.[92] In their study of 732 patients over 5.5 years, Cohen et al[93] found that only 23% of
patients reacted exclusively to allergen(s) on a similar (but not identical) standard series, 37% reacted to allergens on both
their standard series and other supplementary tests, and 40% reacted only to supplementary allergens. Thus, to maximally
benefit patients, practitioners of patch testing must use allergens beyond those deemed appropriate for commercial sale by the
Food and Drug Administration. In the case of fragrance allergens, Larsen et al[94] found that the addition of a "natural mix" of
2% jasmine absolute, 2% ylang-ylang oil, 2% narcissus absolute, 2% sandalwood oil, and 2% spearmint oil increased the
sensitivity of detecting fragrance allergy to 95% from the 81% detected with the standard allergens, fragrance mix and balsam
of Peru.
In vitro tests for the diagnosis of ACD have received much attention in the last decade of the 20th century. Laboratory studies
such as lymphocyte transformation or macrophage migration inhibition have been evaluated as measurements of ACD in both
humans and animals.[95] One of the major problems in developing in vitro systems is the lack of knowledge about what
constitutes the antigenic moiety of a particular chemical. Nonetheless, these assays are now being extensively studied and
reliably standardized.[96] In data submitted by the Interagency Coordinating Committee on the Validation of Alternative
Methods (ICCVAM), the local lymph node assay (LLNA, a test of lymphocyte transformation) did not accurately predict all
weak sensitizers (false-negative) and some strong irritants (false-positive).[97] However, when the LLNA was compared with
currently accepted methods (ie, guinea pig methods), the LLNA performed equivalently in the prediction of the risk for human
ACD. In a review of 209 chemicals, of which both LLNA and guinea pig data were available for 126 chemicals and both
LLNA and human data were provided for 74 chemicals, the accuracy of the LLNA versus all guinea pig tests (GPTs) was
86% and versus human data was 72%, whereas that of all GPTs versus human tests was 73%.[98] In terms of accuracy,
sensitivity, specificity, and positive/negative predictability, the ICCVAM found the performance of the LLNA to be similar to
that of GPTs. Equally important, the performance of the LLNA and the GPT was similar when each was compared with
human data. Thus, although in vivo patch testing in which the skin can process the allergen for presentation remains the "gold
standard" for the near future, the new millennium brings exciting prospects for in vitro testing.
TREATMENT AND PREVENTION
The treatment of ACD lies in correctly identifying its cause and in instructing the patient to avoid the responsible allergen(s).
Because many allergens may share common antigenic moieties, the practitioner must also instruct the patient about possible
cross-reacting allergens. For example, the patient allergic to benzocaine must potentially avoid many cross-reacting
substances, which include agents as diverse as other anesthetics (eg, procaine), certain medications (eg, sulfonamides), hair
dyes (eg, para-phenylenediamine), textile dyes (eg, aniline dyes), some sunscreens (eg, para-aminobenzoic acid), and other
products. Because cross-reactions are not always evident to the nonchemist (eg, benzoyl peroxide with cocaine), practitioners
must consult standard texts[99] [100] when instructing their patients.
In addition to avoidance of the allergen and its cross-reactants, treatment of ACD should be directed to its symptoms. This is
particularly true because, as is evident from numerous studies, patients with ACD will not always improve with avoidance of
allergens and job changes.[101] Pryce et al[102] showed that more than 70% of machinists continued to have symptoms of
contact dermatitis 2 years after diagnosis, regardless of whether they changed jobs. Halbert et al[103] showed that almost 70%
of their patients continued to have a dermatitis for years after the diagnosis of chromate allergy, despite avoidance. They
further showed that the chronicity of the dermatitis increased when the diagnosis was delayed longer than 12 months, thus
stressing the need for early diagnostic intervention. As demonstrated by Lips et al,[104] if the disorder is diagnosed early, if strict
allergen avoidance is enforced by authorities, and if financial support exists for job retraining, the prognosis is often good.
However, in the United States and other countries where the social safety net is more porous, persons with chronic contact
dermatitis may well retain it in some form despite continuing therapy, a finding that has serious implications for Worker's
Compensation.
Acute weeping eruptions benefit from drying agents such as topical aluminum sulfate-calcium acetate; chronic lichenified
eruptions are best treated with emollients. Pruritus can be controlled with topical antipruritics or oral antihistamines; topical
antihistamines or anesthetics should be avoided because of the risk of inducing a secondary allergy in already dermatitic skin.
Treatment with physicochemical agents that down-regulate responsiveness may also be required; glucocorticoids and UV
radiation are the clinical agents most widely used. Although topical glucocorticosteroids usually suffice for most patients with
ACD, individuals with involvement of greater than 25% of their body surface area or those exposed to certain allergens (such
as Toxicodendron oleoresin, which appears to persist locally in the skin for weeks after exposure) may require systemic
glucocorticosteroids. In some of these patients phototherapy with UVB or PUVA can be beneficial, especially for those
individuals with occupational ACD who are economically unable to discontinue working with the offending allergen and who
are also unable to work with gloves or effective barrier creams. In these cases, long-term maintenance therapy with UVB[105]
or PUVA[106] may obviate clinical manifestations of the allergy despite persistent contact. In this millennium potential
therapeutic modalities include new classes of immunosuppressants (topical FK 506, ascomycin), inhibitors of cellular
metabolic activity, inhibitors of cell adhesion molecules, targeted skin application of regulatory cytokines, and neutralization of
proinflammatory cytokines with antisense oligonucleotides, anticytokine antibodies, or soluble cytokine receptors.[107] [109]
Although prevention of ACD rests with avoidance of the allergen, for various reasons, principally economic, this is not always
possible. The hairdresser allergic to glyceryl thioglycolate (in acid permanent solutions), which can persist in hair for months[110]
and can penetrate vinyl and latex gloves,[99] may be unable to avoid daily contact with the allergen. A plastic glove made of
proprietary laminate has been introduced (4H, available from Safety 4, Lenexa, Kan; URL, http://www.safety4.com
). In clinical trials the 4H glove, which is only 0.07 mm thick, was impervious to more than 90% of all randomly selected
organic chemicals for 4 hours at 35°C. [111] However, this glove is not form fitting and is thought by many professionals to
impede the fine dexterity needed in their work. In the future, barrier creams may be available to help such patients. Now,
however, barrier creams are available for only a limited number of allergens (principally poison ivy and poison oak), are
effective only if the protected area is washed within several hours of contact with the allergen, and are objectionable to many
patients because of their thick tack and greasy consistency. Thus the search for suitable alternatives continues. A recent article
has touted the benefit of ginkgo biloba in a sodium carboxy-methyl-beta-1,3-glucan formulation as a protectant against ACD
induced by nickel, fragrance, balsam of Peru, and MCI/MI.[112]
Although the possibility of hyposensitization for ACD has intrigued researchers for decades, it currently is not a viable
alternative. Despite the early encouraging work of Schamberg [113] and Strickler[114] with oral or intramuscular
Toxicodendron antigen to desensitize the Rhus-allergic individual, such therapy has never been clearly found to be effective.
In his exhaustive study, Kligman[115] concluded that complete desensitization of the highly sensitive subject by oral or
intramuscular administration is impossible. In these studies, months of treatment with Toxicodendron oleoresin resulted in a
temporary lessening of the intensity of the allergic response but not an ablation of it. In another study in which the active
ingredients of Rhus oleoresin (pentadecylcatechol and heptadecylcatechol) were fed to 44 patients, no effect was seen.[116]
One theoretic possibility for prevention of occupational ACD is the induction of tolerance to the known occupational allergens
before employment. When an antigen to which an individual has not yet been sensitized is administered either systemically[24]
or topically to areas deficient in functional LCs,[25] long-lived tolerance ensues. However, because allergic reactions to
apparently innocuous materials, such as nickel, persist in the human genotype, it must be questioned whether there is a
selective advantage to the trait. It cannot be assumed that simple chemical allergens do not cross-react with viral or
tumor-related antigens. In the absence of information concerning how the antigenic moieties of many simple chemicals might
relate to antigenically more complex viruses and malignancies, it would seem unethical to induce tolerance to even the most
problematic environmental allergens given the theoretic risk of enhancing susceptibility to potentially more life-threatening
diseases. Hopefully, the solution to this and other dilemmas surrounding ACD will be found early in this millennium.
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CONTACT DERMATITIS
Contact dermatitis is inflammation of the skin caused by exposure to one of many antigens or irritants. Several classifications of
contact dermatitis exist, including allergic, irritant, photodermatitis, and contact urticaria. Allergic contact dermatitis (ACD) is a
type IV hypersensitivity reaction (ie, non-IgE, cell-mediated delayed hypersensitivity) caused by many different agents, the
most common of which are plants of the Rhus (Toxicodendron) genus (poison ivy, poison oak, poison sumac), [7] nickel,
potassium dichromate, and paraphenylenediamine. [8] In elderly patients, the most common offending agents are topical
medications. [9] Appearance of lesions occurs within 24 to 96 hours after exposure to the allergen. [10] When the etiologic
agent of ACD is unknown, patch testing can be helpful for identification. [10]
Irritant contact dermatitis (ICD) is caused by direct local epidermal cytotoxic effect of the irritant and is also caused by various
agents, including acids, alkalis, solvents, and oxidants. [8] The severity of the skin reaction in ICD is usually relative to the
amount of agent and to the total contact time. [10] Patients at the extremes of age are generally more susceptible to ICD. [11]
The chief complaint in ICD is usually pain and burning, whereas in ACD pruritis predominates. [10]
Most forms of contact dermatitis appear similarly. Acutely, the area of skin contact develops a well-localized area of vesicles
filled with clear fluid on an erythematous base. [8] Oozing and eroding skin develops as vesicles break open. Elderly patients
usually have an intensely pruritic scaling rather than a vesiculating pattern, with lichenification and hyperpigmentation presenting
early on. [9] In contrast to acute dermatitis, subacute dermatitis is seen as multiple papules with less associated edema. Chronic
dermatitis presents as minimally swollen, scaly, and occasionally lichenified lesions. [8] In most instances, contact dermatitis
resolves within 3 to 4 weeks after removal of the inciting agent. [8]
In phototoxic and photoallergic contact dermatitis, irradiation with ultraviolet or visible light converts certain substances into
irritants or allergens. Phototoxic reactions are nonimmunologically mediated, appearing as first-degree burns with patients
complaining of burning. In contrast, photoallergic reactions are type IV hypersensitivity reactions that require prior
sensitization; pruritis is the chief complaint. Agents implicated in photodermatitis include certain dyes, tars, plant products (eg,
psoralens), and drugs (eg, sulfonamides, sulfonylureas, tetracyclines, griseofulvin, and thiazides). [10] [11] Lesions may persist for
years and lichenification and hyperpigmentation may result. [11]
The term contact urticaria comprises several different clinical forms, all of which share the onset of symptoms within several
minutes to an hour after skin is exposed to rapidly absorbable agents. [12] Contact urticaria may be classified mechanistically
into the following groups: (1) immunologically mediated, (2) nonimmunologically mediated, and (3) uncertain mechanism
mediated.
Immunological contact urticaria is characterized by a wheal-and-flare response at the site of skin contact with an inciting
agent.F1 Organs other than the skin may be involved and anaphylactic shock is a possible outcome. [10] [12] Atopic patients
have a higher incidence of immunologically mediated urticaria than patients without atopy. As in other forms of immediate
hypersensitivity, immunological contact urticaria is an IgE-mediated process, which ultimately results in the release of
inflammatory mediators such as histamine. [12] This form of urticaria requires prior exposure to the specific agent. Food is a
very common inciting agent, and patients often present within 30 minutes of handling food, with symptoms ranging from itching
to erythema and urticarial swelling. Recently, latex has been implicated in immunologically mediated contact urticaria, and has
been seen frequently in health care workers who require the use of rubber gloves. [13] [14] [15]
Nonimmunological contact urticaria is seen more commonly than immunological urticaria. Local erythema and edema results
when the skin comes into contact with common agents such as benzoic acid, sorbic acid, cinnamic acid, and nicotinic acid
esters. These urticants are found in ice cream, soft drinks, chewing gum, shampoos, perfumes, mouthwashes, creams, and
ointments. Patients may complain of burning and itching alone or in combination with erythema, or may present with erythema
without pruritis. Other organ systems are uninvolved. Because immune mechanisms are not involved, symptoms may appear
on first exposure to the agent. Non-antibody-mediated release of prostaglandins or leukotrienes may be a possible mechanism
of nonimmunologic urticaria. [12]
Agents that cause contact urticaria that is not clearly immunologically related are classified as having an uncertain mechanism.
Three examples of this type of urticaria are ammonium persulfate, solar, and aquagenic urticaria. [11] [12] Ammonium persulfate,
a hair bleaching agent, can cause first-exposure urticaria but also may lead to systemic involvement. Solar urticaria may occur
within 5 to 30 minutes of sun exposure, and may represent a hypersensitivity to a normal photoproduct. Hives appear around
hair follicles in aquagenic urticaria after exposure to water, saline, or the patient's own sweat or sebum; a toxic mast cell
degranulating agent found in sebum may be the causative agent.
The differential diagnosis of contact dermatitis includes atopic dermatitis, dyshidrotic eczema, psoriasis, herpes simplex and
herpes zoster, insect bites, drug eruptions, erythema multiforme, pustular lesions on the palms and soles, scabies, erysipelas,
and lichen planus. [10] [11]
Treatment of contact dermatitis consists of avoidance of irritants, Burow's solution (aluminum acetate) in combination with wet
compresses for 15 to 20 minutes at a time several times daily, and topical corticosteroids for acute cases. [8] [10] [11] Topical
corticosteroids without the use of compresses are used to treat subacute and chronic dermatitis. Systemic corticosteroids are
occasionally required for severe cases or patients with more than 30% body involvement. [7] [8] Antihistamines may also be
given to relieve itching. Restriction of sunlight exposure and the use of protective
590
clothing may limit the development of lesions in patients with photodermatitis.
In addition to avoidance of the offending agents, the use of chlorpheniramine-like antihistamines is useful in the treatment of
contact urticaria; terfenadine and astemizole are less efficacious antihistamines. [11] Nonsteroidal anti-inflammatory agents
(NSAIDs) may be useful for nonimmunological contact urticaria via inhibition of prostaglandin and leukotriene release. [11]
Anaphylactic reactions are treated in the usual manner, ie, epinephrine, intravenous fluids, steroids, antihistamines, and
vasopressors if required.