Contact Dermatitis

Background

Contact dermatitis is a very common and probably underreported disease. It can range from cases of irritation with an underarm anti-perspirant to Poison Ivy exposure. Allergic Patch testing may be helpful in determining potential allergens.

Outline

Epidemiology
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Differential Diagnosis
Prognosis and Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY CHARACTERIZATION

INCIDENCE

Occupational dermatitis in a 10-year material.

Fregert S.

Section of Occupational Dermatology, University Hospital, Lund, Sweden.
Contact Dermatitis 1975;1(2):96-107 Abstract quote
This study included 1,752 patients considered to have occupational dermatoses. The most common diagnosis was contact dermatitis. The dermatitis was of an allergic type in three-quarters of men and in half of women. One-fifth of the women with irritant contact dermatitis had an atopic history. Contact dermatitis was localized on the hands in 94% of women and in 84% of men.

The most common allergens in men were chromium, rubber and plastic, and in women nickel, rubber and chromium. Chromium allergy occurred in four-fifths of the men in the building, metal and tanning industries. In one-fifth of the women, nickel allergy developed in cleaning work. Rubber allergy developed in the rubber industry in one-fifth of the cases. Half of the women with contact dermatitis were engaged in either nursing or cleaning work.

A follow-up 2-3 years after treatment of 555 patients with contact dermatitis was completed by means of questionnaires. The eczema was healed in one-quarter of the patients, one-half had periodic symptoms, and one-quarter had permanent symptoms. The prognosis was the same for those who changed their work or stopped working as it was for those who continued their eczema-inducing work.

Occupational allergic contact dermatitis is more prevalent than irritant contact dermatitis: A 5-year study.

Kucenic MJ, Belsito DV.

University of Kansas Medical Center, Kansas City, Kansas.
J Am Acad Dermatol 2002 May;46(5 Pt 1):695-9 Abstract quote
BACKGROUND: Irritant contact dermatitis is thought to be the leading cause of occupational skin disease in the United States. Recent reports suggest otherwise.

OBJECTIVES: The purposes of this study were to determine the prevalence of allergic and irritant forms of occupational contact dermatitis in the population seen at a Midwestern dermatologic referral clinic, report professions commonly affected by occupational skin disease, and indicate which substances are frequent allergens.

METHODS: A retrospective analysis of patch test data collected at the University of Kansas between 1994 and 1999 was performed.

RESULTS: Of 537 patients who underwent patch testing, 135 (25%) had occupational skin disease. Allergic contact dermatitis affected 81 (60%) patients, and irritant contact dermatitis was found in 46 (34%). Health care professionals, machinists, and construction workers accounted for nearly half of all patients with occupational skin disease. Nickel sulfate, glutaraldehyde, and thiuram mix were the most common allergens.

CONCLUSION: Patch tests with a wider array of allergens than those currently available in the United States are needed to prevent misdiagnosis of occupational contact dermatitis.

PATHOGENESIS CHARACTERIZATION

BACKGROUND

Early inflammatory markers in elicitation of allergic contact dermatitis.

Martin AP, Gallino N, Gagliardi J, Ortiz S, Ruiz Lascano A, Diller A, Daraio MC, Kahn A, Mariani AL, Serra HM.
BMC Dermatol 2002 Aug 7;2(1):9 Abstract quote
Background: Allergic Contact Dermatitis (ACD) is regarded as a T-cell-mediated delayed-type hypersensitivity reaction. We studied the kinetics of the expression of CS-1 fibronectin, thymus and activation-regulated chemokine (CCL17/ TARC) and different chemokine receptors (CR) in skin biopsies from individuals challenged in their back with the antigen responsible of their contact dermatitis and an irrelevant antigen.

Methods: Samples were taken at 2, 10, and 48 hours for histological and immunohistochemical studies using monoclonal antibodies against human CS-1 fibronectin, CCL17, CD3, CD68, CD49d, CXCR3, CCR5,and CCR3.

Results: At positive antigen stimulated sites there was an early expression of CS-1 fibronectin (2 hours), followed by CCL17 and a later accumulation of alplha4/beta1+ (CD49d), CD3+, CD68+, CXCR3+ and CCR5+ mononuclear cells. At 48 hours, approximately 59 % of infiltrating cells were CXCR3+, 42% CCR5+, and only 14 % CCR3+.

Conclusions: These results showed for the first time a very early expression of CS-1 fibronectin which preceded production of CCL17 in blood endothelial cells (BCEs) from patients' skin with ACD. The role of these molecules in recruitment of monocytes and effector T cells in ACD is discussed.

CD1a CELLS

CD1a-positive dendritic cells transport the antigen DNCB intracellularly from the skin to the regional lymph nodes in the induction phase of allergic contact dermatitis.

Hunger RE, Yawalkar N, Braathen LR, Brand CU.

Dermatological Clinic, University of Berne, Switzerland.

Arch Dermatol Res 2001 Aug;293(8):420-6 Abstract quote

Dendritic cells are potent stimulators of T cell-mediated immune responses. In contact hypersensitivity reactions in animals dendritic cells have been reported to transport antigens to the regional lymph nodes.

In this study we investigated whether skin-derived dendritic cells transport contact antigens via the afferent lymph in humans. By means of a microsurgical technique lymph cells were collected after painting a defined skin region with a 2% concentration of the sensitizing agent 2,4-dinitrochlorobenzene on the leg of 14 volunteers. There was no significant change in flow, output or composition of cells after antigen painting. Using flow cytometric analysis we were able to detect the antigen in CD1a+ dendritic cells of the afferent lymph 15-25 h after antigen application. The antigen could only be detected after permeabilizing the dendritic cells, indicating that the main part of the antigen is transported intracellularly and not on the surface of these cells. Further analysis of cell surface antigens such as CD80, CD86, HLA-DR, CD11a, CD14, CD23, CD25 and CD54 revealed that in the course of cutaneous sensitization the phenotype of the dendritic cells was not altered in the afferent lymph.

These results provide direct evidence that during the induction phase of allergic contact dermatitis in humans antigen-bearing dendritic cells internalize the antigen and migrate from the skin via the afferent lymph vessels to the lymph nodes.

CS-1 FIBRONECTIN

Vascular endothelium express CS-1 fibronectin in allergic contact dermatitis.

Martin AP, Ortiz S, Cabalier ME, Frede S, Burgos E, Hliba E, Serra H.

Inmunologia, Hospital Nacional de Clinicas, Universidad Nacional de Cordoba, Cordoba, Argentina Patologia, Facultad Cs. Quimicas, Hospital Nacional de Clinicas, Universidad Nacional de Cordoba, Cordoba, Argentina Cat. Dermatologia, Hospital Nacional de Clinicas, Universidad Nacional de Cordoba, Cordoba, Argentina.
J Cutan Pathol 2002 Jul;29(6):347-353 Abstract quote
Background: Allergic contact dermatitis (ACD) is a common human dermatosis in which not all the mechanisms involved in its pathogenesis have been elucidated. Objective: To study the expression of CS-1 fibronectin, TARC and Th1-associated chemokine receptors in biopsies from allergic patch test reactions.

Material and methods: Thirteen patients already diagnosed with ACD were challenged on the back with the antigen responsible of the disease and macroscopic responses and biopsies taken after 48 h. Skin biopsies from negative control challenge sites, AD and ICD were also taken. Samples were fixed, embedded in paraffin wax and processed in order to perform histological and immunohistochemical studies.

Results: All subjects with ACD showed a positive clinical response and a perivascular mononuclear cell infiltration at 48 h, which was not seen in the negative controls. The majority of skin-infiltrating cells were CD4+ and CD8+ and up to 54% or 40% of them expressed CXCR3 or CCR5, respectively. We also showed expression of CS-1 fibronectin in inflamed endothelial cells not only in ACD but also in AC and ICD. In contrast TARC was only expressed in ACD and AC.

Conclusion: We showed for the first time that CS-1 fibronectin is expressed in dermal vessels from allergic patch tests positive reactions, as well as irritant and atopic skin lesions.

LABORATORY/RADIOLOGIC/
OTHER TESTS
CHARACTERIZATION

RADIOLOGIC

LABORATORY MARKERS

Comparative study of Finn Chambers and T.R.U.E. test methodologies in detecting the relevant allergens inducing contact dermatitis

Tina Suneja, MD
Donald V. Belsito, MD

Kansas City, Kansas

J Am Acad Dermatol 2001;45:836-9 Abstract quote

T.R.U.E. Test is a ready-to-use patch test system, which contains 23 allergens and is the only Food and Drug Administration-approved source of allergens currently commercially available in the United States. Previously, allergens dispersed in either petrolatum or water and designed to be applied utilizing Finn Chambers were also commercially available in the United States.

During a 5-year study at the University of Kansas Medical Center, 167 patients were patch tested using both Finn Chamber and T.R.U.E. Test methodologies. Discordant positive reactions were examined for clinical relevance. The Finn Chamber methodology was superior in detecting clinically relevant allergies to fragrance mix, balsam of Peru, and thiuram mix. T.R.U.E. Test performed somewhat better than the Finn Chamber in detecting relevant allergic reactions to nickel, neomycin, and methylchloroisothiazolinone/methylisothiazolinone.

Neither T.R.U.E. Test nor Finn Chamber methodologies performed optimally in detecting relevant allergies to formaldehyde and carbamates.

Practitioners limited to only the T.R.U.E. Test methodology need to be aware that relevant reactions to fragrances, rubber accelerators/pesticides (carbamates and thiurams), and formaldehyde may be missed with this system.

GROSS APPEARANCE/
CLINICAL VARIANTS CHARACTERIZATION

GENERAL

VARIANTS

ANGRY BACK SYNDROME

Angry back syndrome is often due to marginal irritants: a study of 17 cases seen over 4 years.

Cockayne SE, Gawkrodger DJ.

Department of Dermatology, Royal Hallamshire Hospital, Sheffield, UK.

Contact Dermatitis 2000 Nov;43(5):280-2 Abstract quote

17 patients with angry back syndrome were identified over a 4-year period (1994-97).

10 such patients were classified as multiple reactors and 7 as exacerbations of atopic eczema. The 10 multiple reactors reacted most commonly to medicaments, rubber chemicals, fragrances, methylchloroisothiazolinone/methylisothiazolinone, colophonium and nickel. A final diagnosis of relevant allergic contact dermatitis was made in 8 of the 10 patients with multiple reactions. Relevant contact allergens were rubber chemicals, plants, metals and preservatives, all of which can be marginal irritants. None of the reactions in the patients with exacerbation of dermatitis were thought to be relevant or helpful in the further management of the patient.

Reactions in the angry back syndrome appear to be due most commonly to marginal irritants. In multiple reactors, marginal irritants were also the most common allergens finally identified.

BUDESONIDE

Allergic contact dermatitis in response to budesonide reactivated by inhalation of the allergen.

Isaksson M, Bruze M.

Department of Occupational and Environmental Dermatology, Malmo University Hospital.
J Am Acad Dermatol 2002 Jun;46(6):880-5 Abstract quote
BACKGROUND: Up to 5% of patients with dermatitis who are consecutively patch tested are allergic to one or more corticosteroids. However, few reports of allergic mucosal and skin symptoms in patients with asthma and rhinitis caused by inhaled corticosteroids exist.

OBJECTIVE: Our purpose was to determine whether inhalation of budesonide would result in reactivation of patch test reactions caused by budesonide.

METHODS: The study, which was randomized, double-blind, and placebo-controlled, was ethically reviewed by the Medical Faculty, University of Lund, Sweden. Fifteen nonasthmatic patients who were initially given a diagnosis of budesonide hypersensitivity on patch testing from less than 1 up to 8 years before the study were provoked with budesonide or placebo by inhalation 6 weeks after they had been patch tested with budesonide, its R and S diastereomers, and potentially cross-reacting substances. Lung function was studied by using spirometry and repeated peak expiratory flow measurements.

RESULTS: In 4 of 7 patients who inhaled budesonide, reactivation of previously positive patch test reactions was noted within 24 hours, in contrast to 0 of 8 patients who inhaled placebo (P =.026). No adverse pulmonary responses could be detected.

CONCLUSION: This study shows that allergic skin reactions may occur in patients with contact allergy to budesonide when inhaled forms of the drug are used.

COPPER

Copper allergy revisited

Stefan W�hrl, MD, MS
Wolfgang Hemmer, PhD
Margarete Focke, PhD
Manfred G�tz, MD
Reinhart Jarisch, MD

Vienna, Austria

J Am Acad Dermatol 2001;45:863-70. Abstract quote

Background: Positive patch tests to copper sulfate are regularly observed, although copper is reported as a rare allergen with a low sensitizing potential. Usually they are claimed to be irritant and unspecific.

Objective: The aim of this study was to assess the relevance and the diagnostic value of positive reactions to copper. Methods: A total of 2660 routine patch tests were analyzed for positive reactions to copper and other metal allergens: copper, 3.53%; nickel, 21.02%; palladium, 5.90%; cobalt, 3.31%.

Results: Reactions to copper and nickel were highly significantly associated with each other. Twenty-six patients with a positive routine test to copper were retested. The reproducibility was modest (38%), but again significantly associated with nickel sensitization.

Conclusion: These clinical data support a copper-nickel cross-reactivity concept on T-cell level based on recently published molecular data. We conclude that positive patch tests to copper are mostly specific; however, they are usually of low clinical relevance.

DETERGENT

Allergic contact dermatitis to detergents: A multicenter study to assess prevalence

Donald V. Belsito, MD
Anthony F. Fransway, MD
Joseph F. Fowler Jr, MD, etal.

Kansas City, Kansas; Fort Meyers, Florida; Louisville, Kentucky; Winston-Salem, North Carolina; San Francisco, California; Hershey, Pennsylvania; Cincinnati, Ohio; New Orleans, Louisiana; Portland, Oregon; and Baltimore, Maryland

J Am Acad Dermatol 2002;46:200-6 Abstract quote

Background: Allergic contact dermatitis (ACD) to optical brighteners and enzymes in laundry detergents was the focus of numerous reports in the early 1970s. Subsequently, there has been little published on the incidence of allergic reactions to chemicals in laundry detergents. Nonetheless, consumers and physicians continue to ascribe allergic contact reactions to laundry detergents.

Objective: This article reports the findings of a multicenter study on the prevalence of patch test reactions to a liquid and a granular laundry detergent provided by Procter & Gamble Company (Cincinnati, Ohio).

Methods: Patients referred to members of the North American Contact Dermatitis Group for evaluation of potential ACD were invited to participate in the study, which involved the placement of 2 patch tests (a 0.1% aqueous dilution of a granular laundry detergent and a 0.1% aqueous dilution of a liquid laundry detergent). Whether the patients had atopic dermatitis and whether they or their physicians felt that their dermatitis might be related to laundry detergents were noted. Reactions to the laundry detergents were correlated with allergic reactions to the following screening chemicals: fragrances, nickel, and potassium dichromate. Patients who experienced a reaction to at least one of the laundry detergents could enter phase II of the study, which involved testing to varying dilutions of the laundry detergents, to 0.1% sodium lauryl sulfate (as an irritant control), and to laundered patches of cotton. Patients positive in phase II could enter phase III, which involved wearing a garment laundered with the detergent. Phases II and III were double blinded.

Results: Of the 3120 patients seen by members of the North American Contact Dermatitis Group during the 2 years of this study, 738 patients volunteered to enroll. Enrollment was not statistically randomized. Of these 738, 5 (0.7%) had positive patch test reactions to granular laundry detergent (0.1%, aqueous); 3 of these 5 also had positive reactions to the liquid laundry detergent (0.1%, aqueous). In 4 of the 5 patients, the reaction to detergent was thought to have present relevance to their dermatitis; in 1 of the 5, the reaction was deemed to have past relevance. One of these 5 patients had allergy to fragrances. None of the patients was positive to nickel or chromate. Two of the 5 entered phases II and III. Of these 2 patients, 1 had essentially negative repeat dilutional patch testing and �use testing� suggesting that the earlier reaction patterns may have been irritant. The remaining patient had positive dilutional reactions to both the liquid and granular laundry detergent; however, she also had a positive reaction to sodium lauryl sulfate and to a swatch from a T-shirt laundered without detergent. Upon �use testing� in phase III, this latter patient experienced diffuse dermatitis under both the half of the T-shirt laundered with detergent and that laundered without detergent. Conclusion: Laundry detergents appear to be a rare cause of ACD. Among 738 patients with dermatitis, 5 (0.7%) reacted to a 0.1% aqueous dilution of a laundry detergent. Only 2 of these 5 patients could be evaluated in greater detail to differentiate allergic from irritant patch test reactions to detergents. Upon further testing in 2 patients, the reaction in 1 of 2 could not be reduplicated and the reaction in the other was invoked both by the detergents and the controls.

Thus, whether our study patients were truly allergic and, if so, what the allergenic material(s) in detergents might be, remains unknown. Therefore the reported incidence rate for detergent-induced allergy of 0.7% in dermatitic patients may be too high, possibly because of false-positive irritant reactions.

EMLA

EMLA(R) cream-induced irritant contact dermatitis.

Dong H, Kerl H, Cerroni L.

Department of Dermatology, University of Graz, Austria, Department of Dermatology, The First Teaching Hospital, Medical University of Henan, Public Republic of China.
J Cutan Pathol 2002 Mar;29(3):190-2 Abstract quote
BACKGROUND: The Eutectic Mixture of Local Anesthetics (EMLA(R) cream) is a topical anesthetic used for providing pain relief in patients undergoing superficial surgical procedures. Cutaneous side-effects have been reported rarely.

CASE REPORT: We present a case of irritant contact dermatitis induced by EMLA(R) cream in a 6-year-old boy with Wiskott-Aldrich syndrome. Our patient showed clinically a well circumscribed patch corresponding to the site of application of the topical anesthetic. Histopathology showed confluent necrosis of keratinocytes in the upper epidermis, a mixed inflammatory infiltrate with priminent neutrophils in the upper dermis, and focal signs of interface changes including basal cell vacuolization and subepidermal cleft formation.

CONCLUSIONS: Graft-vs.-host-disease (GVHD), necrolytic migratory erythema, dermatitis enteropathica and pellagra should be considered in the histopathologic differential diagnosis of acute contact dermatitis caused by EMLA(R).

METHOXYPSORALEN

Systemic allergic contact dermatitis to 8-methoxypsoralen (8-MOP)

Jane Ravenscroft, MBChB MRCP
Victoria Goulden, MBChB MRCP
Mark Wilkinson, MD MRCP

Leeds, England

J Am Acad Dermatol 2001;45:S218-9. Abstract quote

Photochemotherapy with psoralens and UVA (PUVA) is widely used in the treatment of psoriasis and many other skin conditions. Cutaneous adverse reactions to 8-methoxypsoralen (8-MOP) appear to be rare and may be difficult to distinguish from phototoxicity or UV-induced polymorphic light eruption.

We describe a patient who had a systemic allergic contact dermatitis to 8-MOP develop during her second course of PUVA treatment for psoriasis.

MINOXIDIL

Allergic contact dermatitis to topical minoxidil solution: Etiology and treatment

Edward S. Friedman, BS
Paul M. Friedman, MD
David E. Cohen, MD MPH
Ken Washenik, MD, PhD

J Am Acad Dermatol 2002;46:309-12 Abstract quote

After more than a decade of use, topical minoxidil solution has proven to be a safe and effective treatment for androgenetic alopecia. However, some patients present with complaints of pruritus and scaling of the scalp. The most common causes of these symptoms include irritant contact dermatitis, allergic contact dermatitis, or an exacerbation of seborrheic dermatitis. Patients suffering from allergic contact dermatitis may benefit from patch testing to determine the causative allergen.

Among the patients we patch tested, propylene glycol was found to be the contactant in a majority of cases, not the minoxidil itself. Many of these patients may be candidates for treatment with alternative formulations using other solvents, such as butylene glycol, polysorbate, or glycerol.

Although predictive, patch testing results do not ensure that the compounded preparations will be tolerated. Unfortunately, patients found to be allergic to minoxidil are no longer candidates for topical treatment of their alopecia with any preparations of minoxidil.

OSMIUM TETROXIDE

Traumatic osmium tetroxide inoculation

Jeff J. Ligon, MD
Jerrold L. Abraham, MD
Alan S. Boyd, MD

Nashville, Tennessee, and Syracuse, New York

J Am Acad Dermatol 2001;45:949-52. Abstract quote

Osmium tetroxide is a highly oxidizing, corrosive compound commonly found in electron microscopy laboratories. Although osmium tetroxide is known to cause rapid damage to organic tissue, its cutaneous effects have not been well studied.

We report a case of traumatic inoculation from a broken vial of 4% osmium tetroxide. Electron microscopy and energy dispersive x-ray spectroscopy confirmed the presence of osmium in the tissue specimen. The lesion was treated by simple excision.

PHOTOALLERGIC CONTACT

Photoallergic contact dermatitis is uncommon.

Darvay A, White IR, Rycroft RJ, Jones AB, Hawk JL, McFadden JP.

Department of Environmental Dermatology, St John's Institute of Dermatology, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, U.K.

Br J Dermatol 2001 Oct;145(4):597-601 Abstract quote

Background
Despite the enormous increase in sunscreen use, allergic contact (AC) and photoallergic (PA) reactions to ultraviolet (UV) filters are considered rare.

Objectives
To analyse the data from 2715 patients who underwent photopatch testing at St John's Institute of Dermatology during the period 1983-98.

Methods
A retrospective analysis of all positive photopatch test episodes was undertaken with the results retrieved from the environmental dermatology database and further verified with the original archived patch test documentation for each individual patient.

Results
In 111 patients with positive reactions (4.1%), there were 155 AC or PA reactions to allergens in the photopatch test series. Eighty PA reactions were observed in 62 (2.3%) patients (32 men and 30 women, age range 28-75 years), with UV filters accounting for 52 positive reactions (65%), drugs 16 (20%), musk ambrette 11 (14%) and the antiseptic trichlorocarbanilide one (1%). The most common UV filter photoallergen was benzophenone-3 with 14 positive results, followed by benzophenone-10 (n = 9), isopropyl dibenzoylmethane (n = 6), p-aminobenzoic acid (PABA) (n = 5), octyl dimethyl PABA (n = 5), butyl methoxydibenzoylmethane (n = 4), isoamyl methoxycinnamate (n = 2), ethyl methoxycinnamate (n = 2), octyl methoxycinnamate (n = 2), amyl dimethyl PABA (n = 2) and phenylbenzimidazole sulphonic acid (n = 1). A similar number of AC reactions to UV filters was detected in this study. Thus 49 patients (1.8%) had a total of 75 reactions: 51 due to UV filters and 24 as a result of exposure to fragrances and therapeutic agents. Benzophenone-10 accounted for 13 AC reactions and benzophenone-3 for eight reactions. Twenty-two patients had a PA reaction alone, whereas 19 patients had chronic actinic dermatitis and 15 patients polymorphic light eruption (PLE) in addition. Thus, 34 of the 62 patients (55%) had a preceding underlying photodermatosis.

Conclusions
These results show a low yield of positive photopatch tests. Thus, despite the large increase in the use of UV filters over the last decade, the development of PA reactions remains rare. Furthermore, most of the common UV filter photoallergens identified in this study, including PABA, amyl dimethyl PABA and benzophenone-10, are now rarely used in sunscreen manufacture, while isopropyl dibenzoylmethane was voluntarily removed from the market in 1993. Currently, benzophenone-3 is the commonest contact photoallergen still in widespread use. In contrast, the UVB filter octyl methoxycinnamate, used in a number of sunscreens, produced only two positive PA reactions in 12 years of testing. Nevertheless, although these reactions are extremely rare, patients with photodermatoses such as PLE and chronic actinic dermatitis do represent a group of patients at increased risk of developing photoallergy. Further photopatch test series should be regularly reviewed and updated, as the relevance of individual photoallergens changes over time. Currently, there is no evidence that PA reactions represent a common clinical problem.

PROGNOSIS AND TREATMENT CHARACTERIZATION

PROGNOSTIC FACTORS

TREATMENT Removal of offending allergen
Topical or systemic steroid treatment

Weedon D. Weedon's Skin Pathology. Churchill Livingstone. 1997.
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.

Commonly Used Terms

Rashes

Internet Links

Last Updated 8/16/2002

Send mail to psdermpath@earthlink.net with questions or comments about this web site.
Copyright � 2002 The Doctor's Doctor

EPIDEMIOLOGY	CHARACTERIZATION
INCIDENCE
Occupational dermatitis in a 10-year material. Fregert S. Section of Occupational Dermatology, University Hospital, Lund, Sweden.	Contact Dermatitis 1975;1(2):96-107 Abstract quote This study included 1,752 patients considered to have occupational dermatoses. The most common diagnosis was contact dermatitis. The dermatitis was of an allergic type in three-quarters of men and in half of women. One-fifth of the women with irritant contact dermatitis had an atopic history. Contact dermatitis was localized on the hands in 94% of women and in 84% of men. The most common allergens in men were chromium, rubber and plastic, and in women nickel, rubber and chromium. Chromium allergy occurred in four-fifths of the men in the building, metal and tanning industries. In one-fifth of the women, nickel allergy developed in cleaning work. Rubber allergy developed in the rubber industry in one-fifth of the cases. Half of the women with contact dermatitis were engaged in either nursing or cleaning work. A follow-up 2-3 years after treatment of 555 patients with contact dermatitis was completed by means of questionnaires. The eczema was healed in one-quarter of the patients, one-half had periodic symptoms, and one-quarter had permanent symptoms. The prognosis was the same for those who changed their work or stopped working as it was for those who continued their eczema-inducing work.
Occupational allergic contact dermatitis is more prevalent than irritant contact dermatitis: A 5-year study. Kucenic MJ, Belsito DV. University of Kansas Medical Center, Kansas City, Kansas.	J Am Acad Dermatol 2002 May;46(5 Pt 1):695-9 Abstract quote BACKGROUND: Irritant contact dermatitis is thought to be the leading cause of occupational skin disease in the United States. Recent reports suggest otherwise. OBJECTIVES: The purposes of this study were to determine the prevalence of allergic and irritant forms of occupational contact dermatitis in the population seen at a Midwestern dermatologic referral clinic, report professions commonly affected by occupational skin disease, and indicate which substances are frequent allergens. METHODS: A retrospective analysis of patch test data collected at the University of Kansas between 1994 and 1999 was performed. RESULTS: Of 537 patients who underwent patch testing, 135 (25%) had occupational skin disease. Allergic contact dermatitis affected 81 (60%) patients, and irritant contact dermatitis was found in 46 (34%). Health care professionals, machinists, and construction workers accounted for nearly half of all patients with occupational skin disease. Nickel sulfate, glutaraldehyde, and thiuram mix were the most common allergens. CONCLUSION: Patch tests with a wider array of allergens than those currently available in the United States are needed to prevent misdiagnosis of occupational contact dermatitis.

PATHOGENESIS	CHARACTERIZATION
BACKGROUND
Early inflammatory markers in elicitation of allergic contact dermatitis. Martin AP, Gallino N, Gagliardi J, Ortiz S, Ruiz Lascano A, Diller A, Daraio MC, Kahn A, Mariani AL, Serra HM.	BMC Dermatol 2002 Aug 7;2(1):9 Abstract quote Background: Allergic Contact Dermatitis (ACD) is regarded as a T-cell-mediated delayed-type hypersensitivity reaction. We studied the kinetics of the expression of CS-1 fibronectin, thymus and activation-regulated chemokine (CCL17/ TARC) and different chemokine receptors (CR) in skin biopsies from individuals challenged in their back with the antigen responsible of their contact dermatitis and an irrelevant antigen. Methods: Samples were taken at 2, 10, and 48 hours for histological and immunohistochemical studies using monoclonal antibodies against human CS-1 fibronectin, CCL17, CD3, CD68, CD49d, CXCR3, CCR5,and CCR3. Results: At positive antigen stimulated sites there was an early expression of CS-1 fibronectin (2 hours), followed by CCL17 and a later accumulation of alplha4/beta1+ (CD49d), CD3+, CD68+, CXCR3+ and CCR5+ mononuclear cells. At 48 hours, approximately 59 % of infiltrating cells were CXCR3+, 42% CCR5+, and only 14 % CCR3+. Conclusions: These results showed for the first time a very early expression of CS-1 fibronectin which preceded production of CCL17 in blood endothelial cells (BCEs) from patients' skin with ACD. The role of these molecules in recruitment of monocytes and effector T cells in ACD is discussed.
CD1a CELLS
CD1a-positive dendritic cells transport the antigen DNCB intracellularly from the skin to the regional lymph nodes in the induction phase of allergic contact dermatitis. Hunger RE, Yawalkar N, Braathen LR, Brand CU. Dermatological Clinic, University of Berne, Switzerland.	Arch Dermatol Res 2001 Aug;293(8):420-6 Abstract quote Dendritic cells are potent stimulators of T cell-mediated immune responses. In contact hypersensitivity reactions in animals dendritic cells have been reported to transport antigens to the regional lymph nodes. In this study we investigated whether skin-derived dendritic cells transport contact antigens via the afferent lymph in humans. By means of a microsurgical technique lymph cells were collected after painting a defined skin region with a 2% concentration of the sensitizing agent 2,4-dinitrochlorobenzene on the leg of 14 volunteers. There was no significant change in flow, output or composition of cells after antigen painting. Using flow cytometric analysis we were able to detect the antigen in CD1a+ dendritic cells of the afferent lymph 15-25 h after antigen application. The antigen could only be detected after permeabilizing the dendritic cells, indicating that the main part of the antigen is transported intracellularly and not on the surface of these cells. Further analysis of cell surface antigens such as CD80, CD86, HLA-DR, CD11a, CD14, CD23, CD25 and CD54 revealed that in the course of cutaneous sensitization the phenotype of the dendritic cells was not altered in the afferent lymph. These results provide direct evidence that during the induction phase of allergic contact dermatitis in humans antigen-bearing dendritic cells internalize the antigen and migrate from the skin via the afferent lymph vessels to the lymph nodes.
CS-1 FIBRONECTIN
Vascular endothelium express CS-1 fibronectin in allergic contact dermatitis. Martin AP, Ortiz S, Cabalier ME, Frede S, Burgos E, Hliba E, Serra H. Inmunologia, Hospital Nacional de Clinicas, Universidad Nacional de Cordoba, Cordoba, Argentina Patologia, Facultad Cs. Quimicas, Hospital Nacional de Clinicas, Universidad Nacional de Cordoba, Cordoba, Argentina Cat. Dermatologia, Hospital Nacional de Clinicas, Universidad Nacional de Cordoba, Cordoba, Argentina.	J Cutan Pathol 2002 Jul;29(6):347-353 Abstract quote Background: Allergic contact dermatitis (ACD) is a common human dermatosis in which not all the mechanisms involved in its pathogenesis have been elucidated. Objective: To study the expression of CS-1 fibronectin, TARC and Th1-associated chemokine receptors in biopsies from allergic patch test reactions. Material and methods: Thirteen patients already diagnosed with ACD were challenged on the back with the antigen responsible of the disease and macroscopic responses and biopsies taken after 48 h. Skin biopsies from negative control challenge sites, AD and ICD were also taken. Samples were fixed, embedded in paraffin wax and processed in order to perform histological and immunohistochemical studies. Results: All subjects with ACD showed a positive clinical response and a perivascular mononuclear cell infiltration at 48 h, which was not seen in the negative controls. The majority of skin-infiltrating cells were CD4+ and CD8+ and up to 54% or 40% of them expressed CXCR3 or CCR5, respectively. We also showed expression of CS-1 fibronectin in inflamed endothelial cells not only in ACD but also in AC and ICD. In contrast TARC was only expressed in ACD and AC. Conclusion: We showed for the first time that CS-1 fibronectin is expressed in dermal vessels from allergic patch tests positive reactions, as well as irritant and atopic skin lesions.

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
VARIANTS
ANGRY BACK SYNDROME
Angry back syndrome is often due to marginal irritants: a study of 17 cases seen over 4 years. Cockayne SE, Gawkrodger DJ. Department of Dermatology, Royal Hallamshire Hospital, Sheffield, UK.	Contact Dermatitis 2000 Nov;43(5):280-2 Abstract quote 17 patients with angry back syndrome were identified over a 4-year period (1994-97). 10 such patients were classified as multiple reactors and 7 as exacerbations of atopic eczema. The 10 multiple reactors reacted most commonly to medicaments, rubber chemicals, fragrances, methylchloroisothiazolinone/methylisothiazolinone, colophonium and nickel. A final diagnosis of relevant allergic contact dermatitis was made in 8 of the 10 patients with multiple reactions. Relevant contact allergens were rubber chemicals, plants, metals and preservatives, all of which can be marginal irritants. None of the reactions in the patients with exacerbation of dermatitis were thought to be relevant or helpful in the further management of the patient. Reactions in the angry back syndrome appear to be due most commonly to marginal irritants. In multiple reactors, marginal irritants were also the most common allergens finally identified.
BUDESONIDE
Allergic contact dermatitis in response to budesonide reactivated by inhalation of the allergen. Isaksson M, Bruze M. Department of Occupational and Environmental Dermatology, Malmo University Hospital.	J Am Acad Dermatol 2002 Jun;46(6):880-5 Abstract quote BACKGROUND: Up to 5% of patients with dermatitis who are consecutively patch tested are allergic to one or more corticosteroids. However, few reports of allergic mucosal and skin symptoms in patients with asthma and rhinitis caused by inhaled corticosteroids exist. OBJECTIVE: Our purpose was to determine whether inhalation of budesonide would result in reactivation of patch test reactions caused by budesonide. METHODS: The study, which was randomized, double-blind, and placebo-controlled, was ethically reviewed by the Medical Faculty, University of Lund, Sweden. Fifteen nonasthmatic patients who were initially given a diagnosis of budesonide hypersensitivity on patch testing from less than 1 up to 8 years before the study were provoked with budesonide or placebo by inhalation 6 weeks after they had been patch tested with budesonide, its R and S diastereomers, and potentially cross-reacting substances. Lung function was studied by using spirometry and repeated peak expiratory flow measurements. RESULTS: In 4 of 7 patients who inhaled budesonide, reactivation of previously positive patch test reactions was noted within 24 hours, in contrast to 0 of 8 patients who inhaled placebo (P =.026). No adverse pulmonary responses could be detected. CONCLUSION: This study shows that allergic skin reactions may occur in patients with contact allergy to budesonide when inhaled forms of the drug are used.
COPPER
Copper allergy revisited Stefan W�hrl, MD, MS Wolfgang Hemmer, PhD Margarete Focke, PhD Manfred G�tz, MD Reinhart Jarisch, MD Vienna, Austria	J Am Acad Dermatol 2001;45:863-70. Abstract quote Background: Positive patch tests to copper sulfate are regularly observed, although copper is reported as a rare allergen with a low sensitizing potential. Usually they are claimed to be irritant and unspecific. Objective: The aim of this study was to assess the relevance and the diagnostic value of positive reactions to copper. Methods: A total of 2660 routine patch tests were analyzed for positive reactions to copper and other metal allergens: copper, 3.53%; nickel, 21.02%; palladium, 5.90%; cobalt, 3.31%. Results: Reactions to copper and nickel were highly significantly associated with each other. Twenty-six patients with a positive routine test to copper were retested. The reproducibility was modest (38%), but again significantly associated with nickel sensitization. Conclusion: These clinical data support a copper-nickel cross-reactivity concept on T-cell level based on recently published molecular data. We conclude that positive patch tests to copper are mostly specific; however, they are usually of low clinical relevance.
DETERGENT
Allergic contact dermatitis to detergents: A multicenter study to assess prevalence Donald V. Belsito, MD Anthony F. Fransway, MD Joseph F. Fowler Jr, MD, etal. Kansas City, Kansas; Fort Meyers, Florida; Louisville, Kentucky; Winston-Salem, North Carolina; San Francisco, California; Hershey, Pennsylvania; Cincinnati, Ohio; New Orleans, Louisiana; Portland, Oregon; and Baltimore, Maryland	J Am Acad Dermatol 2002;46:200-6 Abstract quote Background: Allergic contact dermatitis (ACD) to optical brighteners and enzymes in laundry detergents was the focus of numerous reports in the early 1970s. Subsequently, there has been little published on the incidence of allergic reactions to chemicals in laundry detergents. Nonetheless, consumers and physicians continue to ascribe allergic contact reactions to laundry detergents. Objective: This article reports the findings of a multicenter study on the prevalence of patch test reactions to a liquid and a granular laundry detergent provided by Procter & Gamble Company (Cincinnati, Ohio). Methods: Patients referred to members of the North American Contact Dermatitis Group for evaluation of potential ACD were invited to participate in the study, which involved the placement of 2 patch tests (a 0.1% aqueous dilution of a granular laundry detergent and a 0.1% aqueous dilution of a liquid laundry detergent). Whether the patients had atopic dermatitis and whether they or their physicians felt that their dermatitis might be related to laundry detergents were noted. Reactions to the laundry detergents were correlated with allergic reactions to the following screening chemicals: fragrances, nickel, and potassium dichromate. Patients who experienced a reaction to at least one of the laundry detergents could enter phase II of the study, which involved testing to varying dilutions of the laundry detergents, to 0.1% sodium lauryl sulfate (as an irritant control), and to laundered patches of cotton. Patients positive in phase II could enter phase III, which involved wearing a garment laundered with the detergent. Phases II and III were double blinded. Results: Of the 3120 patients seen by members of the North American Contact Dermatitis Group during the 2 years of this study, 738 patients volunteered to enroll. Enrollment was not statistically randomized. Of these 738, 5 (0.7%) had positive patch test reactions to granular laundry detergent (0.1%, aqueous); 3 of these 5 also had positive reactions to the liquid laundry detergent (0.1%, aqueous). In 4 of the 5 patients, the reaction to detergent was thought to have present relevance to their dermatitis; in 1 of the 5, the reaction was deemed to have past relevance. One of these 5 patients had allergy to fragrances. None of the patients was positive to nickel or chromate. Two of the 5 entered phases II and III. Of these 2 patients, 1 had essentially negative repeat dilutional patch testing and �use testing� suggesting that the earlier reaction patterns may have been irritant. The remaining patient had positive dilutional reactions to both the liquid and granular laundry detergent; however, she also had a positive reaction to sodium lauryl sulfate and to a swatch from a T-shirt laundered without detergent. Upon �use testing� in phase III, this latter patient experienced diffuse dermatitis under both the half of the T-shirt laundered with detergent and that laundered without detergent. Conclusion: Laundry detergents appear to be a rare cause of ACD. Among 738 patients with dermatitis, 5 (0.7%) reacted to a 0.1% aqueous dilution of a laundry detergent. Only 2 of these 5 patients could be evaluated in greater detail to differentiate allergic from irritant patch test reactions to detergents. Upon further testing in 2 patients, the reaction in 1 of 2 could not be reduplicated and the reaction in the other was invoked both by the detergents and the controls. Thus, whether our study patients were truly allergic and, if so, what the allergenic material(s) in detergents might be, remains unknown. Therefore the reported incidence rate for detergent-induced allergy of 0.7% in dermatitic patients may be too high, possibly because of false-positive irritant reactions.
EMLA
EMLA(R) cream-induced irritant contact dermatitis. Dong H, Kerl H, Cerroni L. Department of Dermatology, University of Graz, Austria, Department of Dermatology, The First Teaching Hospital, Medical University of Henan, Public Republic of China.	J Cutan Pathol 2002 Mar;29(3):190-2 Abstract quote BACKGROUND: The Eutectic Mixture of Local Anesthetics (EMLA(R) cream) is a topical anesthetic used for providing pain relief in patients undergoing superficial surgical procedures. Cutaneous side-effects have been reported rarely. CASE REPORT: We present a case of irritant contact dermatitis induced by EMLA(R) cream in a 6-year-old boy with Wiskott-Aldrich syndrome. Our patient showed clinically a well circumscribed patch corresponding to the site of application of the topical anesthetic. Histopathology showed confluent necrosis of keratinocytes in the upper epidermis, a mixed inflammatory infiltrate with priminent neutrophils in the upper dermis, and focal signs of interface changes including basal cell vacuolization and subepidermal cleft formation. CONCLUSIONS: Graft-vs.-host-disease (GVHD), necrolytic migratory erythema, dermatitis enteropathica and pellagra should be considered in the histopathologic differential diagnosis of acute contact dermatitis caused by EMLA(R).
METHOXYPSORALEN
Systemic allergic contact dermatitis to 8-methoxypsoralen (8-MOP) Jane Ravenscroft, MBChB MRCP Victoria Goulden, MBChB MRCP Mark Wilkinson, MD MRCP Leeds, England	J Am Acad Dermatol 2001;45:S218-9. Abstract quote Photochemotherapy with psoralens and UVA (PUVA) is widely used in the treatment of psoriasis and many other skin conditions. Cutaneous adverse reactions to 8-methoxypsoralen (8-MOP) appear to be rare and may be difficult to distinguish from phototoxicity or UV-induced polymorphic light eruption. We describe a patient who had a systemic allergic contact dermatitis to 8-MOP develop during her second course of PUVA treatment for psoriasis.
MINOXIDIL
Allergic contact dermatitis to topical minoxidil solution: Etiology and treatment Edward S. Friedman, BS Paul M. Friedman, MD David E. Cohen, MD MPH Ken Washenik, MD, PhD	J Am Acad Dermatol 2002;46:309-12 Abstract quote After more than a decade of use, topical minoxidil solution has proven to be a safe and effective treatment for androgenetic alopecia. However, some patients present with complaints of pruritus and scaling of the scalp. The most common causes of these symptoms include irritant contact dermatitis, allergic contact dermatitis, or an exacerbation of seborrheic dermatitis. Patients suffering from allergic contact dermatitis may benefit from patch testing to determine the causative allergen. Among the patients we patch tested, propylene glycol was found to be the contactant in a majority of cases, not the minoxidil itself. Many of these patients may be candidates for treatment with alternative formulations using other solvents, such as butylene glycol, polysorbate, or glycerol. Although predictive, patch testing results do not ensure that the compounded preparations will be tolerated. Unfortunately, patients found to be allergic to minoxidil are no longer candidates for topical treatment of their alopecia with any preparations of minoxidil.
OSMIUM TETROXIDE
Traumatic osmium tetroxide inoculation Jeff J. Ligon, MD Jerrold L. Abraham, MD Alan S. Boyd, MD Nashville, Tennessee, and Syracuse, New York	J Am Acad Dermatol 2001;45:949-52. Abstract quote Osmium tetroxide is a highly oxidizing, corrosive compound commonly found in electron microscopy laboratories. Although osmium tetroxide is known to cause rapid damage to organic tissue, its cutaneous effects have not been well studied. We report a case of traumatic inoculation from a broken vial of 4% osmium tetroxide. Electron microscopy and energy dispersive x-ray spectroscopy confirmed the presence of osmium in the tissue specimen. The lesion was treated by simple excision.
PHOTOALLERGIC CONTACT
Photoallergic contact dermatitis is uncommon. Darvay A, White IR, Rycroft RJ, Jones AB, Hawk JL, McFadden JP. Department of Environmental Dermatology, St John's Institute of Dermatology, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, U.K.	Br J Dermatol 2001 Oct;145(4):597-601 Abstract quote Background Despite the enormous increase in sunscreen use, allergic contact (AC) and photoallergic (PA) reactions to ultraviolet (UV) filters are considered rare. Objectives To analyse the data from 2715 patients who underwent photopatch testing at St John's Institute of Dermatology during the period 1983-98. Methods A retrospective analysis of all positive photopatch test episodes was undertaken with the results retrieved from the environmental dermatology database and further verified with the original archived patch test documentation for each individual patient. Results In 111 patients with positive reactions (4.1%), there were 155 AC or PA reactions to allergens in the photopatch test series. Eighty PA reactions were observed in 62 (2.3%) patients (32 men and 30 women, age range 28-75 years), with UV filters accounting for 52 positive reactions (65%), drugs 16 (20%), musk ambrette 11 (14%) and the antiseptic trichlorocarbanilide one (1%). The most common UV filter photoallergen was benzophenone-3 with 14 positive results, followed by benzophenone-10 (n = 9), isopropyl dibenzoylmethane (n = 6), p-aminobenzoic acid (PABA) (n = 5), octyl dimethyl PABA (n = 5), butyl methoxydibenzoylmethane (n = 4), isoamyl methoxycinnamate (n = 2), ethyl methoxycinnamate (n = 2), octyl methoxycinnamate (n = 2), amyl dimethyl PABA (n = 2) and phenylbenzimidazole sulphonic acid (n = 1). A similar number of AC reactions to UV filters was detected in this study. Thus 49 patients (1.8%) had a total of 75 reactions: 51 due to UV filters and 24 as a result of exposure to fragrances and therapeutic agents. Benzophenone-10 accounted for 13 AC reactions and benzophenone-3 for eight reactions. Twenty-two patients had a PA reaction alone, whereas 19 patients had chronic actinic dermatitis and 15 patients polymorphic light eruption (PLE) in addition. Thus, 34 of the 62 patients (55%) had a preceding underlying photodermatosis. Conclusions These results show a low yield of positive photopatch tests. Thus, despite the large increase in the use of UV filters over the last decade, the development of PA reactions remains rare. Furthermore, most of the common UV filter photoallergens identified in this study, including PABA, amyl dimethyl PABA and benzophenone-10, are now rarely used in sunscreen manufacture, while isopropyl dibenzoylmethane was voluntarily removed from the market in 1993. Currently, benzophenone-3 is the commonest contact photoallergen still in widespread use. In contrast, the UVB filter octyl methoxycinnamate, used in a number of sunscreens, produced only two positive PA reactions in 12 years of testing. Nevertheless, although these reactions are extremely rare, patients with photodermatoses such as PLE and chronic actinic dermatitis do represent a group of patients at increased risk of developing photoallergy. Further photopatch test series should be regularly reviewed and updated, as the relevance of individual photoallergens changes over time. Currently, there is no evidence that PA reactions represent a common clinical problem.

LABORATORY/RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
RADIOLOGIC
LABORATORY MARKERS
Comparative study of Finn Chambers and T.R.U.E. test methodologies in detecting the relevant allergens inducing contact dermatitis Tina Suneja, MD Donald V. Belsito, MD Kansas City, Kansas	J Am Acad Dermatol 2001;45:836-9 Abstract quote T.R.U.E. Test is a ready-to-use patch test system, which contains 23 allergens and is the only Food and Drug Administration-approved source of allergens currently commercially available in the United States. Previously, allergens dispersed in either petrolatum or water and designed to be applied utilizing Finn Chambers were also commercially available in the United States. During a 5-year study at the University of Kansas Medical Center, 167 patients were patch tested using both Finn Chamber and T.R.U.E. Test methodologies. Discordant positive reactions were examined for clinical relevance. The Finn Chamber methodology was superior in detecting clinically relevant allergies to fragrance mix, balsam of Peru, and thiuram mix. T.R.U.E. Test performed somewhat better than the Finn Chamber in detecting relevant allergic reactions to nickel, neomycin, and methylchloroisothiazolinone/methylisothiazolinone. Neither T.R.U.E. Test nor Finn Chamber methodologies performed optimally in detecting relevant allergies to formaldehyde and carbamates. Practitioners limited to only the T.R.U.E. Test methodology need to be aware that relevant reactions to fragrances, rubber accelerators/pesticides (carbamates and thiurams), and formaldehyde may be missed with this system.

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSTIC FACTORS
TREATMENT	Removal of offending allergen Topical or systemic steroid treatment