Irritant or allergic contact dermatitis usually presents as an eczematous process, clinically characterized by erythematoedematovesicous lesions with intense itching in the acute phase. Such manifestations become erythematous-scaly as the condition progresses to the subacute phase and papular-hyperkeratotic in the chronic phase. Not infrequently, however, contact dermatitis presents with noneczematous features. The reasons underlying this clinical polymorphism lie in the different noxae and contact modalities, as well as in the individual susceptibility and the various targeted cutaneous structures. The most represented forms of non-eczematous contact dermatitis include the erythema multiforme-like, the purpuric, the lichenoid, and the pigmented kinds. These clinical entities must obviously be discerned from the corresponding “pure” dermatitis, which are not associated with contact with exogenous agents.
Allergic contact dermatitis (ACD) is a common cutaneous eczematous disorder caused by contact (either direct or aeromediated) with a range of environmental substances. Pathogenetically, ACD results from an immune reaction involving both innate and adaptive immunologic mechanisms. In particular, hyperreactive response to small chemicals (haptens) penetrating the skin depends on a series of events, such as haptens capability to activate and mobilize cutaneous dendritic cells (cDC), generation of hapten-epitopes for T-cell recognition, and hapten-cDC complex ability to prime effector T cells with skin homing proprieties [
Clinics of ACD are generally polymorphic. Besides the classic eczematous form, in fact, different noneczematous clinical variants are possible [
Factors determining the peculiar polymorphic clinical features of allergic contact dermatitis.
Eruptive polymorphism | |
Evolutive polymorphism | |
Causative agent | |
Patient sensitizing level | |
Way of exposition (cutaneous, systemic) | |
Means of exposition (cutaneous direct, cutaneous aeromediated) | |
Tissue structures targeted by the causative agent | |
Anatomophysiology of the cutaneous region involved | |
Causative agent possible concomitant irritant action | |
Environmental factors (UV, temperature, humidity) | |
Itching intensity variability | |
Preexisting dermatitis underlying the overlapping contact allergy |
Different types of noneczematous contact eruptions.
Erythema multiforme-like contact dermatitis |
Purpuric contact dermatitis |
Lichenoid contact dermatitis |
Lymphomatoid contact dermatitis |
Pigmented contact dermatitis |
Pustular contact dermatitis |
Dyshidrosiform contact dermatitis |
Of all noneczematous clinical variants, the erythema multiforme-like (or “contact erythema multiforme”) is the most common. It can be elicited by different substances, particularly exotic woods, medicaments, and ethylenediamine (Table
Causative allergens in erythema multiforme-like eruption.
Plants and woods | Medicaments | Miscellaneous chemicals |
---|---|---|
|
Ethylenediamine | Brominated compounds |
|
Pyrrolnitrin | Phenylsulphone derivatives |
|
Sulfamide | Epoxy resin |
|
Econazole | Formaldehyde |
|
Promethazine | Disperse blue 124 |
|
Balsam of Peru | Trichloroethylene |
|
Scopolamine | Dinitrochlorobenzene |
Capsicum | Mafenide acetate | Diphenylcyclopropenone |
Terpenes | Proflavine | |
Pyrethrum | Neomycin | |
Mephenesin | ||
Vitamin E | ||
Budesonide | ||
Bufexamac | ||
Clioquinol (vioform) | ||
Ketoprofen | ||
Triamcinolone acetonide | ||
Idoxuridine | ||
Phenylbutazone |
Other reported causes of erythema multiforme-like reactions include
Early lesions are eczematous in morphology and localized at the allergen contact site. After a 1 to 15 days delay, the erythema multiforme-like eruption follows, involving the area around the original lesions or rather extending to the whole cutaneous surface. The latter occurrence generally ensues systemic exposition to drugs which the patient had previously been sensitized to topically. Target-like, erythematovesicular, or urticarial lesions are characteristic. Resolution is slow-paced; these manifestations persist usually much longer than the original eczematous lesions (or sometimes appearing after regression of the latter). Itching sensation is also typically present in polymorphic reactions [
Differential diagnosis is set out with true erythema multiforme (Table
Differential diagnosis between true erythema multiforme (EM) and erythema multiforme-like contact dermatitis.
Criteria | EM | EM-like contact dermatitis |
---|---|---|
Etiology | Viruses, bacteria, systemic drugs | Various topical chemicals |
| ||
Clinical features | Erythematoedematous lesions with cockade appearance, sometimes bullous, with acral localization (face, hands, forearms, thighs) | Polymorphic lesions located peripherally to the contact site with the sensitizing agent |
| ||
Fever | Often present | Absent |
| ||
Mucosal involvement | Frequent | Rare |
| ||
Histology | Epidermis: basal cells necrosis, subepidermal vesicobullae |
Epidermis: spongiosis |
| ||
Pathogenesis | Immunocomplexes | Type IV hypersensitivity |
| ||
Patch tests | Negative | Positive |
| ||
Course | Self-limited in 3 weeks | Favorable after allergen withdraw |
The histology is generally aspecific. Epidermis shows spongiosis and exocytosis. Mild upper dermis edema and perivascular lymphohistiocytic infiltration are noticeable. Vacuolar degeneration of basal cells is rarely present, while epidermal necrosis is very mild or absent. When bullae are present, they are intraepidermal [
The histopathology of true erythema multiforme shows frank epidermal necrosis and vacuolar basal cells degeneration, while bullae are subepidermal [
This particular form of noneczematous contact dermatitis is of unusual observation, and many cases remain undiagnosed. The eruption evolves in several weeks after the withdrawal of the offending agent and resolves with more or less persistent pigmentation. The purpuric aspects of contact dermatitis, and the respective patch test reactions can be secondary to irritant, or more frequently allergic, mechanisms [
The most frequent causative factors are listed in Table
Causative agents in purpuric contact dermatitis.
Rubber compounds | Textile compounds | Plants | Miscellany |
---|---|---|---|
N-isopropyl-N′-phenyl-paraphenylenediamine | Optical whiteners (Tinopal CH 3566) |
|
Paraphenylenediamine |
Mercaptobenzothiazole | Azoic dyes |
|
Fiberglass |
Rubber compounds | |
Peru balsam | |
Formaldehyde resins | d-Limonene | Epoxy resin | |
Oxyquinoline | |||
Proflavine | |||
Cobalt | |||
Benzoyl peroxide |
A sailor developed generalized purpuric lesion with pigmentary outcomes at sites of contact with the military blue uniform. Patch tests evidenced positive reaction to Disperse Blue 85, while histology demonstrated Schamberg disease sign [
Vasculitic purpuric eruptions to Peru balsam [
As is well known among those who practice dermatoallergology, petechial reactions to cobalt patch test, without edema, vesicles, and infiltration, can be observed. These are toxic in nature rather than allergic. Schmidt et al., in a 4-year time span, observed 123 cases (4.7%) of cobalt petechial reactions out of a total of 2594 patch-tested patients. Twenty-three patients were retested and developed new petechial responses in 60% of cases. Based on these authors data, the incidence of positive allergic reactions to cobalt was lower (2.9%) than the incidence of primary irritant reactions [
Purpuric contact dermatitis can be either toxic or allergic in nature. From a clinical-morphological perspective, differential diagnosis is not straightforward: both present palpable purpuric elements, evolve slowly and are followed by variably intense and persistent pigmentation. At times, clinical extension represents a useful feature in differentiating the 2 forms, the irritant being strictly limited to contact sites. Moreover, lesional elements resolve more rapidly and are less infiltrated in the irritant form compared to the allergic one.
Diffuse contact irritation from fiberglass must be discerned from scabies, eczema (prurigo-like), animal and vegetal acariasis, and if persistent, from Hodgkin disease. The anamnestic data of epidemic bursts in industries or bureaus (fibers dispersed from defective air conditioners) greatly aid diagnosis [
The allergic form of purpuric contact dermatitis generally features diffuse and polymorphic manifestations: papulopurpuric and papulovesicular lesions parallel classic eczematous foci. The latter are limited to the original contact site with the offending noxa. Secondary distant lesions can also present polymorphic or vasculitic aspects, as we have directly observed. Purpuric patch tests reactions are obviously vesicular and infiltrated [
The pathogenetic mechanism of purpuric contact dermatitis is currently unknown. Hemostasis or complement system alterations are not generally described in reported cases nor are immune complexes commonly isolated. In every case we observed, among which 3 severe cases from Peru balsam with frankly vasculitic and bullous lesions and various cases from ethylenediamine (in which the rash had followed systemic administration of aminophylline), specific laboratory exams fell into normal range [
Since endothelial cells degeneration is evident at electron microscopy, a selective effect on these cells has been hypothesized. In detail, specific toxic or allergic substances as well as certain mechanical stimuli (fiberglass) would exhibit an affinity for vessels endothelium [
Histopathology has been described, with comparable results, in most reported cases. In the epidermis, spongiosis and lymphocytic exocytosis are constant features, along with possible bulla formation. In the upper dermis the signs of leukocytoclastic vasculitis (vessels fibrinoid degeneration, edematous endothelium, scarce perivascular lymphomonocytic and neutrophilic infiltrate, erythrocytes extravasation, and karyorrhexis) are visible. The same features are present when examining a patch test response lesion (Table
Histopathological characteristics of purpuric contact dermatitis (PCD) and vasculitis (V).
Criteria | PCD | V |
---|---|---|
|
++ | Negative |
|
+ | ++ |
|
Negative | ++ |
|
+ | +++ |
|
+ | +++ |
|
+ | +++ |
|
Negative | ++ |
Bloodwork, histologic and patch test examinations are valid to differentiate the condition from vascular, hemostatic, and idiopathic purpuric affections.
A particularly uncommon form of noneczematous contact dermatitis presents with clinical features resembling those of lichen planus. It affects both skin and mucosal membranes.
Color developers, substances derived from paraphenylenediamine, are the most common cause of allergic contact lichenoid eruption. Among these compounds, Kodak CD2 (4-N, N-diethyl-2 methylphenylenediamine), Kodak CD3 (4-N-ethyl-N-2-methanesulfonylaminoethyl-2-methyl-phenylenediamine sesquisulfate monohydrate), Kodak CD4 (2-amino-5-N-ethyl-N-(hydroxyethyl)-aminotoluene sulfate), Ilford MI 210 (N-ethyl-N (5-hydroxy-amyl) para-phenylenediamine hydrogen sulphate), and Agfa TSS (4-amino-N-diethylaniline sulfate) [
Other cases of lichenoid contact dermatitis have been reported by Mandel, in 9 out of 11 workers with contact allergy to a color developer [
Eczematous lesions evolve or associate with papulous lesions with peculiar lilac-red gradation. The eruption mostly involves contact sites, later widely spreading with mucosal sparing. Course is prolonged and leaves variably intense pigmentary changes lasting up to some months. Lichenoid contact dermatitis has to be differentiated from lichen planus, with its characteristic papulous polygonal lilac lesions. The onset of lichenoid contact dermatitis is almost invariably acute and the eruption spreads rapidly. Frankly eczematous lesions at the primitive site are noticeable in many cases.
Positive reactions to patch tests are eczematous in nature, but might turn lichenoid.
Pathogenesis of contact lichenoid dermatitis is unclear. Systemic absorption of offending agents can elicit skin lesions far from the original site of contact. In 5 cases we observed (3 from color film developers and 2 from paraphenylenediamine), histology displayed lack of hypergranulosis, foci of moderate spongiosis, and focal basal stratum vacuolization. A patchy mononuclear infiltrate was evident in the upper dermis [
Histopathological characteristics of lichenoid contact dermatitis (LCD) and lichen planus (LP).
Criteria | LCD | LP |
---|---|---|
|
++ | Negative |
|
−/+ | +++ |
|
+ | +++ |
|
+ | +++ |
|
Negative | ++ |
|
Lengthened | Broaden, dome shaped |
|
Mild perivascular | Band-like |
This uncommon dermatitis manifests with the clinical features of plaque parapsoriasis or an early stage mycosis fungoides [
Histology is crucial in differentiating the above two conditions. Spongiosis is much clearer, and exocytosis is typically lymphocytic in contact dermatitis. Mycosis fungoides instead shows atypical lymphocytes in focal abscess-like aggregations (i.e., the pathognomonic Pautrier’s microabscesses) and a band-like subepidermal infiltration of large lymphoid cells with cerebriform nuclei (Table
Histopathological characteristics of lymphomatoid contact dermatitis (LCD) and mycosis fungoides (MF).
Criteria | LCD | MF |
---|---|---|
|
+++ | + |
|
−/+++ |
+++ |
|
Perivascular | Band-type |
|
−/+ | +++ |
Described by Osmundsen in 1970, it is a melanic primitive hyperpigmentation, usually observed in dark phototypes and mostly occupational [
Clinically, involved sites were those of textile contact dermatitis, with brown-blue to grayish hyperchromia. The same occurred at patch test application sites. Histology evidenced melanin deposits inside and out melanophages in the upper dermis.
Pigmented contact dermatitis can also be prompted by azoic dyes. An epidemic outburst from contact to naphthol AS has been reported in a textile business [
Causative agents in pigmented contact dermatitis.
Optical whiteners | Tinopal CH 3566 |
---|---|
Dyes | Naphthol AS |
| |
Cosmetics | Pigments: |
| |
Fragrances | Jasmine |
| |
Antiseptics | Carbanilide |
| |
Miscellany | Formaldehyde |
Pustules are usually associated with irritant reactions. Nevertheless, allergic pustular reactions are known from nitrofurazone [
The implication of such rare pustular reactions remains uncertain. Pustules are sterile and transient and can displace subcorneally, as observed in a case from trichloroethylene [
Pustular reactions to contactants are frequently observed in patch test reading. Hjorth stated that atopics are predisposed to such reactions [
In subjects affected by atopic dermatitis, we often observed such pustular follicular reactions when patch testing with nickel but also with potassium bichromate. Pustules are always sterile, dry promptly, and resolve rapidly. Erythema is mild and the reaction is not pruriginous. Histology, documented in various cases, has always evidenced intraepidermial aggregations of neutrophils, without signs of lymphomonocytic exocytosis or spongiosis. We have always considered these reactions we directly observed irritant in nature [
Certain authors include this condition among noneczematous allergic contact forms [
Primitive dyshidrosiform ACD is instead an expression of systemic contact allergy, of common observation in nickel sensitized patients. Oral challenge test with nickel reproduces the dyshidrosiform eruption in these subjects [
Table
Differential diagnosis between dyshidrosiform ACD and pompholyx.
Characteristics | Dyshidrosiform ACD | Pompholyx |
---|---|---|
|
+++ | +++ |
|
+++ | + |
|
+++ | + |
|
+ | − |
|
+± | +/+++ |
|
Present | Absent |
|
+++ | + |
|
+++ | + |
|
Minute | Large from coalescing |