Welsh et al.

, J Allergy Ther 2014, 5:4

Allergy & Therapy http://dx.doi.org/10.4172/2155-6121.1000185

Review Article Open Access

Contact Dermatitis: Therapeutics When Avoidance Fails

Esperanza Welsh1, Alina Goldenberg2, Oliverio Welsh3 and Sharon E Jacob4*
1
Dermatology Department, Centro de Especialidades Medicas, Monterrey, Mexico
2
University of California, San Diego, School of Medicine; One Miramar St. #929793, La Jolla, CA 92092, USA
3
Department of Dermatology, Universidad Autonoma de Nuevo Leon, Monterrey, Mexico
4
Department of Dermatology, Loma Linda University, Loma Linda, CA and University of California, San Diego, Division of Dermatology, La Jolla, CA 92161, USA

Abstract
Contact dermatitis is one of the leading reasons to visit a dermatologist. There are two main types of contact
dermatitis which result from exposure to chemicals: irritant contact dermatitis, which accounts for 80% of the cases,
and allergic contact dermatitis, which accounts for 15%. Dermatologists must be cognizant of these diagnoses and
consider appropriate and judicious use of the diagnostic patch test procedure. Once a clinically relevant allergen is
diagnosed by patch testing, avoidance is the mainstay of therapy; however, medical management interventions may
need to be employed in recalcitrant cases.

Keywords: Contact dermatitis; Intractable; Avoidance; Therapy be late reactors, and their reaction may only be seen on the delayed
interval reading [1].
Abbreviations: ACD: Allergic Contact Dermatitis; CD:
Contact Dermatitis; ICD: Irritant Contact Dermatitis; TSC: Topical Treatment
Corticosteroids Once the diagnosis of ACD is confirmed by patch testing, the
Allergic Contact Dermatitis Physiology mainstay of therapy is avoidance of the offending allergen. Patient
education is the key to treatment adherence and symptom resolution.
Allergic Contact Dermatitis (ACD) involves the penetration of an Patients need to understand what the substance does to their skin,
allergen through the skin surface where it acts as a hapten by binding where the substance is found and how to avoid it. Additionally,
to epidermal proteins and eliciting, a delayed Type IV hypersensitivity patients need to learn how to read labels and know that substances
reaction 48 to 120 hours after exposure. This immunologic response can be found in other products, even under different names. This
involves the activation of Th1 cells with the subsequent release of educational discussion takes time and patience. Fortunately, there are
cytokines resulting in the classic inflammatory reaction. two very useful tools that can be utilized to properly orient the patient
as to which products he or she can safely use. The Contact Allergen
Patch Testing Management Program (CAMP) and Contact Allergen Replacement
Patch testing is the main tool used for ACD diagnosis. This test Database (CARD) provide patients and physicians with easy-to-access
involves the application of different allergens onto unaffected skin of lists of different products that they can use devoid of the offending
the patients backs. Standard screening series, such as the American agent [2,3].
Contact Dermatitis 80 Series, are available to help direct allergen Although avoidance is the crucial element in trying to help patients
selection process in adults. Additional supplemental allergens may suffering from ACD, it sometimes fails, and exposure is inevitable;
also need to be selected based on the clinical history. The allergens are in these situations the only solution is to try to minimize as much
placed in chambers/wells on hypoallergenic tape and then placed on as possible the inflammatory cascade by utilizing various medical
the skin. In order to effectively perform a patch test, certain guidelines management tools including barrier creams and emollients, topical
must be followed. Firstly, selected test skin must not be inflamed and systemic corticosteroids, cacineurin inhibitors, antihistamines (for
at the time of patch testing application as this may confound the itch and sedation), phototherapy, steroid-sparing immune-modulators
resulting response. Secondly, any excess hair should be shaved prior to and topical and oral retinoids (Table 1).
application (generally a day or two before) to avoid added irritation. The
patients must be advised to avoid any contact with water for 48 hours Barrier Creams and Emollients
after application to decrease the risk of a false negative response, due
to improper adhesion. To further optimize the patch test readability, Barrier creams and emollients physically help decrease exposure
to chemicals by decreasing the permeability and increasing hydration
patients are instructed on the need to avoid topical and systemic
steroids, phototherapy or sun exposure, and immune modulators such
as azathioprine, methotrexate, mycophenolate mofetil, cyclosporine
and biologics, because these could result in a false negative response. *Corresponding author: Sharon E Jacob, Department of Dermatology, Loma
Linda University Health, 11370 Anderson Street, Suite 2600, USA, Tel: 9095582842;
Forty eight hours after application, the patch tests are removed Fax: 9095582874; E-mail: [email protected]
and an initial reading is done. All of the reactive areas are remarked ReceivedMay 13, 2013; Accepted July 22, 2014; Published July 29, 2014
again with a surgical marker to enable re-identification of placement
Citation: Welsh E, Goldenberg A, Welsh O, Jacob SE (2014) Contact Dermatitis:
during the delayed reading (72-120 h post-placement). This technique Therapeutics When Avoidance Fails. J Allergy Ther 5: 185. doi:10.4172/2155-
allows for filtering of any irritant effects which should decrease after 6121.1000185
two days, whereas the true allergic responses will likely crescendo at the Copyright: 2014 Welsh E, et al. This is an open-access article distributed under
later time interval. Of note, some allergens such as neomycin sulfate, the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and
sodium gold thiosulfate, and corticosteroids are reported to potentially source are credited.

J Allergy Ther
ISSN:2155-6121 JAT an open access journal Volume 5 Issue 4 1000185
Citation: Welsh E, Goldenberg A, Welsh O, Jacob SE (2014) Contact Dermatitis: Therapeutics When Avoidance Fails. J Allergy Ther 5: 185.
doi:10.4172/2155-6121.1000185

Page 2 of 4

Treatment type Dose dependent, time to onset the active chemical belongs to and what it is likely to cross react
Topical corticosteroids 1-2 weeks within. TCS were classically divided into five groups based on their
Topical retinoids 2-4 weeks structure: A) hydrocortisone type, B) triamcinolone acetone type, C)
Topical calcineurin inhibitors 8 weeks betamethasone type, D1) betamethasone dipropionatetype and D2)
Phototherapy or sunlight exposure 1-3 months methylprednisolone aceponate type [7]. Recently, this classification
Oral prednisone 1-2 weeks has been revised and simplified into three molecularly distinct groups
Cyclosporine 3-6 weeks arranged in the order of most allergic potential to least: 1) non-
Methotrexate 6-8 weeks methylated, non-halogenate (includes groups A, D2, budesonide);
TNF-alpha inhibitors 1-3 months 2) halogenated with C16/C17 cisketal/diol (includes group B); 3)
Oral retinoids 2-3 months halogenated C16-methylated (includes groups C and D1) [8]. Steroids
Mycophenolate mofetil Up to 3 months within a group have the greatest potential to cross react [7].
Azathioprine 2-6 months
Phototherapy
Table 1: ACD Treatment Duration to Effect Onset [6,25,26].
Phototherapy is an effective option for patients with intractable
of skin [4]. While some products utilize silicone and dimethicone widespread ACD [6]. Ultraviolet light has an immunosuppressive
which act as true barriers, others add natural anti-inflammatory agents effect and has been found to inhibit contact hypersensitivity reactions
such as colloidal oatmeal. Of note, petrolatums are now available with [9]. However, it has the potential side effects of acutely inducing
different size particles making them more cosmetically acceptable. erythema, burning or stinging and increased skin cancer risk with
Barrier creams or emollients should be used to decrease dryness and extended use. Due to its effectiveness, narrow band UVB at 311 nm
inflammation, and potentially minimize the need for topicals such as has largely replaced broadband UVB. Narrowband UVB has been
corticosteroids or calcineurin inhibitors. compared with paint-PUVA (that with topical psoralen pre-treatment)
for the treatment of hand eczema with comparable results [10].
Topical Corticosteroids Phototherapy using UVA or PUVA consists of the administration of
8-methoxypsoralen, for which nausea is a common side-effect. PUVA
Topical Corticosteroids (TSC) are the first line of pharmacologic
has been frequently used to treat ACD of the hands, however with a
treatment for ACD. Their anti-inflammatory effects are multifactorial
risk of inducing phototoxicity [11,12].
and widespread, affecting lymphocytes, monocytes, and
polymorphonuclear cells [5]. Pathophysiologically, TSCs, decrease Systemic Steroids
antigen-presenting function by the Langerhanscells, and reduce
synthesis and secretion of different cytokines such as interleukin-1, Systemic corticosteroid therapy is a useful therapeutic alternative
interleukin-2, interferon gamma, tumor necrosis factor and for those patients with an acute and severe form of contact dermatitis.
granulocyte-monocute-stimulating factor [5]. Lipocortin, which It is important to try to use the minimal amount of steroids (in both
inhibits phospholipase A2, is induced by topical steroids leading to a duration and concentration) needed to control the disease, so as to
marked inflammatory decline [5]. prevent undesirable side effects. Triamcinolone 40 mg IM can be given
for acute dermatoses, however, tapered oral prednisone (at 1 mg/
The choice of which TCS to use will depend on various factors kg/day) is more commonly utilized as it offers the ability to monitor
including the location of the dermatitis, potency of the steroid, ACD improvement or flare on tapering [6]. Of note, whereas 10 mg/
anticipated length of time of the treatment, age of the patient, and day prednisone dosed patients were found to have successful patch
history of any type of hypersensitivity to a particular TCS. Low potency testing results, those on doses of 20 mg or more per day had significant
steroids are recommended for the face, genital area, and potentially suppression of their reaction. If there is chronic contact dermatitis,
occluded areas such as inframammary and axilla, where absorption is it is best to use a steroid sparing immunosuppressive agent to avoid
increased. Additionally, low potency TCS should be limited in their use significant side effects of long-term steroid use, e.g. inhibition of
around the eyes, due to the associated risk of glaucoma [6]. Patients HPA axis and Cushings disease, diabetes, hypertension, peptic ulcer,
should be advised to avoid rubbing their eyes if a TCS will be used osteonecrosis and osteoporosis and risk of opportunistic infections.
on the hands. The vehicle is also of high importance as petrolatum
based vehicles are greasy, but will aid in the penetration and have a Calcineurin Inhibitors
moisturizing effect added, while gels, lotions and foams are better for
Tacrolimus and pimecrolimus are other options for topical
hair bearing areas [4].
therapy. The mechanism of action of these macrolides is the inhibition
In addition to possible increased risk for glaucoma, TCS use may of calcineurin, which blocks the ability to dephosphorylate the
lead to skin atrophy, striae, and potential blockage of the Hypothalamic- transcription factor NFAT-1 (Nuclear Factor of Activated T-cells).
Pituitary Axis (HPA) [6]. The latter will depend on the duration of This then prevents the transcription of the gene encoding for
treatment, area of exposure and potency of the steroid. Especially in interleukin-2, ultimately blocking T-cell activation and proliferation
young children, HPA axis suppression must be monitored with AM [13]. Additionally, topical calcineurin inhibitors block release of
cortisol levels and if needed a metyrapone test or insulin hypoglycemia inflammatory cytokines and mediate the degranulation of mast cells
test. Diabetes, growth retardation, bone loss, and Cushing syndrome leading to decreased pruritus as well as potential adverse effects of
have been reported [6]. burning sensations [14].
If the patient worsens after the application of a TCS, allergy to Tacrolimus and pimecrolimus are approved in the US for the
the steroid or the vehicle should be considered. Patch testing will aid treatment of atopic dermatitis in adults topically in 0.1% and 0.03%
in defining whether the patient is reacting to an active or inactive formulations and in children at 0.03% as a second line therapy.
ingredient in a product. If there is a reaction to the active ingredient Both have been used for contact dermatitis with good results [6].
in the steroid cream, it is important to know which structural class Macrolides have limited side effects mostly burning and stinging and

J Allergy Ther
ISSN:2155-6121 JAT an open access journal Volume 5 Issue 4 1000185
Citation: Welsh E, Goldenberg A, Welsh O, Jacob SE (2014) Contact Dermatitis: Therapeutics When Avoidance Fails. J Allergy Ther 5: 185.
doi:10.4172/2155-6121.1000185

Page 3 of 4

most importantly, do not cause skin atrophy, and can be used safely Patients with levels less than 6.3 U/ml should not get treated with
on sensitive skin such as the eyelids and genitals [6]. A randomized azathioprineit is estimated that 1 in 300 patients will be found to
controlled study comparing tacrolimus to placebo for the treatment have insufficient TMPT levels thus barring azathioprine as a treatment
of nickel allergy showed that it was superior to the vehicle [15]. A option. If they are between 6.3 and 15 U/ml, up to 1 mg/kg can be
meta-analysis evaluating 17 trials comparing tacrolimus 0.03% and given daily, and at levels from 15.1 to 26.4 U/ml the dose should be
0.1% ointment with TCS in pediatric patients and adult patients with given at 2-2.5 mg/kg. Other laboratories to be tested include CBC,
atopic dermatitis concluded that tacrolimus 0.1% ointment is similar in pregnancy test, chemistry profile with liver enzymes, urine analysis and
efficacy to potent TCS [16]. The experience with atopic dermatitis may PPD. Most common side effects include myelosuppression, infections,
be extrapolated to patients with contact dermatitis [17]. hypersensitivity syndrome, gastrointestinal and hepatic effects.
Malignancies including lymphomas and squamous cell carcinomas
Steroid Sparing Immune Modulators have been described associated with its chronic use.
When a patient is unable to use a systemic corticosteroid or Biologics are newer drugs in the armamentarium that can be of
when it will be used for a prolonged time, a steroid sparing agent is benefit when baseline therapies do not work. These drugs will inhibit
a practical approach. Cyclosporine is a calcineurin inhibitor such as different cytokines that play an important role in the inflammatory
tacrolimus and pimecrolimus but it is a much larger molecule. Its main
cascade that occurs in contact dermatitis. Tumor necrosis factor
mode of action is inhibiting IL-2 and interferon gamma. Patients with
inhibitors include etanercept (receptor blockage), infliximab (chimeric
hand dermatitis responded to a 3 mg/kg/day dose for 6 weeks with
monoclonal antibody) and adalimumab (fully humanized monoclonal
good results [18]. Dosages range from 2.5 to 5 mg/kg/day daily. Renal
function and blood pressure need to be monitored closely. Complete antibody). Ustekinumab and IL-12 and IL-23 monoclonal antibody
blood count, liver enzymes and lipid profiles also need to be monitored has been tested on 5 patients with allergic contact dermatitis with no
monthly. response [21]. Further studies are needed to assess their effectiveness
in ACD.
Mycophenolate mofetil is an inhibitor of the de novo purine
biosynthesis targeting activated lymphocytes. It also inhibits dendritic In cases of chronic hand eczema both topical and systemic retinoids
cells, one of the primary antigen processing cells [6]. The drug was have been found effective.Bexarotene has been used topically yielding a
derived from Penicillium stoloniferum, a fermentation product [19]. good response [22].Systemic retinoids such as acitretin and alitretinoin
The usual dose is 2 to 3 grams divided twice daily. It is started at 500 have also been reported to be safe alternatives when other modalities
mg nightly for a week to prevent/monitor for gastrointestinal upset, prove ineffective [23,24].Of note, two different contraceptive measures
then every 2-4 weeks the dose can be increased 500 mg until the need to be enforced if systemic retinoids are used in patients with
therapeutic range is reached (max 3g/d). A CBC with differential, a childbearing potential.
serum chemistry panel, liver enzymes, hepatitis B and C panel, Purified
Protein Derivative (PPD), and pregnancy test need to be checked and Conclusion
monitored monthly. Nausea, diarrhea and abdominal cramps are the
ACD is a very common dermatologic condition that needs to be
most commonly reported adverse reactions. Additionally, the drug
thought of at the office so as to provide the correct diagnosis and best
must be avoided in patients with childbearing potential due to risk of
treatment option for the patient. The clinical history and patch testing
congenital malformations.
are the main diagnostic tools needed to elucidate the offending allergen.
Methotrexate inhibits dihydrofolate reductase, a key enzyme in cell Patient education through careful explanation and usage of databases
proliferation. Folic acid is the natural substrate and is chemically very such as CAMP or CARD will aid the patient in knowing where the
similar. It can be administered orally, intravenously, subcutaneously, allergen is found, and how to avoid it. However, when avoidance is
and intramuscularly. Dosages are generally given once a week and can inevitable, pharmacologic therapy may be the only alternative. Further
be given as a single dose only or divided in three doses in 24 hours. research of newer, steroid-sparing therapies is necessary to expand the
A test dose is started at 5-10 mg and gradually escalated at 2.5 mg therapeutic tool box.
increments until there is clinical response, while trying to minimize
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ISSN:2155-6121 JAT an open access journal Volume 5 Issue 4 1000185
Citation: Welsh E, Goldenberg A, Welsh O, Jacob SE (2014) Contact Dermatitis: Therapeutics When Avoidance Fails. J Allergy Ther 5: 185.
doi:10.4172/2155-6121.1000185

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J Allergy Ther
ISSN:2155-6121 JAT an open access journal Volume 5 Issue 4 1000185