Differential diagnosis of contact dermatitis: A practical-approach review by the EADV Task Force on contact dermatitis.

The diagnosis of eczema ('dermatitis') is mostly clinical and depends on the clinical history and exploratory objective findings (primary lesions, patterns). Contact dermatitis remains as an important condition in the group of eczematous disorders, with important socioeconomic and occupational relevance. Although irritant and allergic contact dermatitis have a different pathogenesis, both are characterized by a rather typical morphology, are triggered by external factors and tend to occur primarily in the area of contact with the exogenous agent. In addition, allergic and irritant dermatitis may also co-exist. The importance of diagnosing contact dermatitis, especially when allergic in nature, is both due to the possibility of avoiding the trigger, and due to its role in aggravating other skin conditions. Nevertheless, the heterogeneity of clinical presentations in daily practice may pose an important challenge for the suspicion and correct diagnosis of contact dermatitis. Furthermore, other conditions, with different pathogenesis and treatment, may clinically simulate contact dermatitis. The Task Force aims to conduct a review of the unifying clinical features of contact dermatitis and characterize its main clinical phenotypes, and its simulators, in order to contribute to an early suspicion or recognition of contact dermatitis and enable a correct differential diagnosis.

Results of patch testing with five fragrance materials hitherto not tested: A dose-finding study in the clinical population.

BACKGROUND: Quantitative risk assessment (QRA) for skin sensitization is used to derive safe use levels of sensitising fragrance ingredients in products. Post-marketing surveillance of the prevalence of contact allergy to these ingredients provides relevant data to help evaluate the performance of these measures. OBJECTIVES: To determine a suitable patch test concentration for five fragrance materials that had hitherto not been tested on a regular basis. These concentrations are then to be used in a surveillance study with patch testing consecutive patients over an extended monitoring period. MATERIALS AND METHODS: Furaneol, CAS.3658-77-3; trans-2-hexenal, CAS.6728-26-3; 4,8-dimethyl-4,9-decadienal, CAS.71077-31-1; longifolene, CAS.475-20-7; benzaldehyde, CAS.10052-7, were patch tested with other fragrance allergens in four clinics. Patch testing was conducted in three rounds, starting with the lowest concentrations of the five ingredients. The doses were increased in the subsequent rounds if no late-appearing positive reactions and virtually no irritant reactions were reported. RESULTS: Overall, 373 patients were tested. No positive allergic reaction was reported to the five ingredients. Patch test results of other fragrance allergens are reported. CONCLUSIONS: The highest test concentrations are each considered safe for patch testing consecutive patients. Further surveillance based on these preparations will evaluate the hypothesis that QRA-driven consumer product levels of these fragrances can prevent sensitization.

Severely compromised supply of patch test allergens in Europe hampers adequate diagnosis of occupational and non-occupational contact allergy. A European Society of Contact Dermatitis (ESCD), European Academy of Allergy and Clinical Immunology (EAACI), European Academy of Dermatology and Venereology (EADV) task forces 'Contact Dermatitis' and 'Occupational Skin Disease' position paper.

Patch testing is the only clinically applicable diagnostic method for Type IV allergy. The availability of Type IV patch test (PT) allergens in Europe, however, is currently scarce. This severely compromises adequate diagnostics of contact allergy, leading to serious consequences for the affected patients. Against this background, the European Society of Contact Dermatitis (ESCD) has created a task force (TF) (i) to explore the current availability of PT substances in different member states, (ii) to highlight some of the unique characteristics of Type IV vs. other allergens and (iii) to suggest ways forward to promote and ensure availability of high-quality patch testing substances for the diagnosis of Type IV allergies throughout Europe. The suggestions of the TF on how to improve the availability of PT allergens are supported by the ESCD, the European Academy of Allergy and Clinical Immunology, and the European Academy of Dermatology and Venereology and intend to provide potential means to resolve the present medical crisis.

Incidence and prevalence of occupational contact dermatitis in hairdressing apprentices: A 3-year prospective cohort study.

BACKGROUND: It is known that a large number of hairdressing apprentices (HA) develop occupational contact dermatitis (OCD) during schooling, but studies that address prevalence of contact sensitization in HAs with hand eczema are missing. OBJECTIVES: To assess the prevalence, incidence rate and clinical characteristics of OCD, including contact sensitization, in a sample of Croatian HAs. MATERIALS AND METHODS: A total of 408 HAs from 25 Croatian towns were examined at the beginning of education and monitored at the end of each school year. Clinical evaluation of skin changes was performed using the Osnabrueck Hand Eczema Severity Index (OHSI). Standard patch test (PT) with baseline and hairdresser series of contact allergens was performed in 46 HAs with skin changes lasting ≥3 months. RESULTS: The overall incidence rate of OCD was 32.3/100 person-years, and the 3-year prevalence 50.3%. Contact sensitization was found in 14 out of 46 (30.3%) HAs, with 10 of these 14 HAs (71.4%) sensitized to specific hairdressing allergens. The strongest reactions were found to PPD. HAs with positive PT had higher OHSI than HAs with negative patch test (median, IQR: 3, 2-4 vs. 2, 2-4). CONCLUSIONS: Contact sensitization to specific hairdressing chemicals was found in 71.4% of HAs with a positive patch test, supporting evidence on the early contact sensitization to occupational allergens among HAs.

Skin Microbiota in Atopic Dermatitis.

The skin microbiota represents an ecosystem composed of numerous microbial species interacting with each other, as well as with host epithelial and immune cells. The microbiota provides health benefits to the host by supporting essential functions of the skin and inhibiting colonization with pathogens. However, the disturbance of the microbial balance can result in dysbiosis and promote skin diseases, such as atopic dermatitis (AD). This review provides a current overview of the skin microbiota involvement in AD and its complex interplay with host immune response mechanisms, as well as novel therapeutic strategies for treating AD focused on restoring skin microbial homeostasis.

A survey of members of the European Surveillance System on Contact Allergy and the EU project "StanDerm" to identify allergens tested in cosmetic series across Europe.

BACKGROUND: There is currently no agreed cosmetic series for use across Europe. OBJECTIVES: To establish allergens currently tested in local and national cosmetic series. METHOD: Members of the European Surveillance System on Contact Allergy and the European Cooperation in Science and Technology project TD1206 ("StanDerm") were surveyed to establish their current practice. RESULTS: A wide range of allergens was tested but there was significant variation between centres on the allergens considered to be important in screening for allergy to cosmetics. The number of allergens tested in addition to the baseline series varied between 2 and 50. CONCLUSIONS: There is a need for further investigation to establish the frequency and relevance of reactions to cosmetic allergens to enable an agreed evidence-based cosmetic series to be produced. Criteria for inclusion need to be established.

Methylisothiazolinone contact allergy in Croatia: Epidemiology and course of disease following patch testing.

BACKGROUND: Methylisothiazolinone (MI) caused an epidemic of contact allergy in Europe, as shown by data from many countries, but no studies from Croatia exist. Also, data are lacking on the severity of allergic contact dermatitis (ACD) caused by MI, and its impact on quality of life and prognosis. OBJECTIVES: To determine the frequency of MI contact allergy among Croatian dermatitis patients, identify causative exposures, assess the impact of disease, and study the prognosis. METHODS: Data were collected for consecutive dermatitis patients with MI contact allergy patch tested in Croatia between November 2, 2015 and November 3, 2016. RESULTS: MI contact allergy was diagnosed in 13.2% of 798 tested patients. The most frequent dermatitis locations were the hands (76%) and face (61%). In 89.3% of patients, MI contact allergy was found to be of current relevance. Considerable severity and impact on daily life of disease was found at the first consultation, but this significantly decreased until follow-up 3 months later. CONCLUSIONS: Patch testing is the standard method for the diagnosis of ACD, and it has been shown to have an important beneficial effect on prognosis. The severity of MI ACD and the impact on daily life emphasize the need for prevention.

Pilot study on a new concept of documenting the clinical relevance of patch test results in contact dermatitis patients.

BACKGROUND: Assessment of the clinical relevance of patch test reactions is an essential part of the diagnostic work-up of patients with (occupational) contact dermatitis. However, final diagnostic information, particularly the clinical relevance of allergic patch test reactions, has hitherto been ill-represented in clinical documentation systems (patch test software) and surveillance registries based on these. OBJECTIVES: To develop, implement as a pilot study, and analyse concerning feasibility and contents a new concept of representing the full scope of diagnostic information utilized in the diagnosis of patients with (occupational) contact dermatitis. METHODS: On the basis of a European working group discussion on items to document and catalogue lists to use for this purpose, an online documentation system to collect data was set up, followed by pilot use involving 9 dermatology departments across Europe. RESULTS: Data on 176 patients with suspected occupational hand dermatitis were included; among these, work-relatedness was confirmed in 150, and in 53 non-occupational aetiology was the sole or a contributory cause. Data were further analysed with regard to occupations, product categories, substances (haptens), source of information on which the evaluation was based, and various combinations of these factors, to illustrate the usefulness of the proposed data representation. CONCLUSIONS: An improved method of data collection is presented that more accurately links allergen to exposure and to clinical disease and patient history, and thus better represents clinical relevance. This enables more precise analysis of the causation of contact dermatitis, occupational or non-occupational, and thereby better targeting of prevention. The development of future databases should incorporate the above considerations to record the results of investigation.

Extended documentation for hand dermatitis patients: Pilot study on irritant exposures.

BACKGROUND: Irritant exposure may be a contributory cause or the sole cause of (occupational) hand dermatitis. However, the documentation of irritant exposures in clinical practice is not standardized. OBJECTIVES: To examine the feasibility and usefulness of a form with different items addressing both occupational and non-occupational irritant exposures in a semiquantitative way. METHODS: Between May 2016 and May 2017, successive patients with work-related hand dermatitis, irrespective of aetiology, were examined in 9 specialized European departments. Department-specific investigation was supplemented with the above proforma. The results were recorded by use of an anonymized secured online documentation system in a pilot study. RESULTS: Altogether, 193 patients were included; 114 females and 79 males, with a mean age of 40 years (range 18-68 years). The most common occupational group comprised healthcare workers (n = 35); occupational exposure of the hands to gloves, dusts and water without detergents of >2 hours/day was seen in 54.5%, 24.4% and 24.3% of patients, respectively. Non-occupational exposures rarely exceeded 2 hours/day. CONCLUSIONS: It is hoped that the set of descriptors will offer a basis for (clinical) epidemiological studies assessing the role of irritant exposures in occupational hand dermatitis, and to support a high level of quality and consistency in daily patient care.

Effect of allergens and irritants on levels of natural moisturizing factor and corneocyte morphology.

BACKGROUND: The irritant sodium lauryl sulfate (SLS) is known to cause a decrease in the stratum corneum level of natural moisturizing factor (NMF), which in itself is associated with changes in corneocyte surface topography. OBJECTIVE: To explore this phenomenon in allergic contact dermatitis. METHODS: Patch testing was performed on patients with previously positive patch test reactions to potassium dichromate (Cr), nickel sulfate (Ni), methylchloroisothiazolinone (MCI)/methylisothiazolinone (MI), or p-phenylenediamine. Moreover, a control (pet.) patch and an irritant (SLS) patch were applied. After 3 days, the stratum corneum from tested sites was collected, and NMF levels and corneocyte morphology, expressed as the amount of circular nanosize objects, quantified according to the Dermal Texture Index (DTI), were determined. RESULTS: Among allergens, only MCI/MI reduced NMF levels significantly, as did SLS. Furthermore, only MCI/MI caused remarkable changes at the microscopic level; the corneocytes were hexagonal-shaped with pronounced cell borders and a smoother surface. The DTI was increased after SLS exposure but not after allergen exposure. CONCLUSIONS: MCI/MI significantly decreased NMF levels, similarly to SLS. The altered corneocyte morphology suggests that skin barrier damage plays a role in the pathogenesis of MCI/MI contact allergy. The DTI seems to differentiate reactions to SLS from those to the allergens tested, as SLS was the only agent that caused a DTI increase.

Stratum Corneum Tape Stripping: Monitoring of Inflammatory Mediators in Atopic Dermatitis Patients Using Topical Therapy.

OBJECTIVE: The aim of this study was to explore the tape strip sampling technique in the assessment of stratum corneum levels of inflammatory mediators in a clinical trial setting. METHODS: Thirty-eight inflammatory mediators were analyzed by a multiplex-assay in the stratum corneum, collected by adhesive tapes before and after 6 weeks of therapy, in mild and moderate atopic dermatitis (AD) patients (n = 90). Treatment was a ceramide- and magnesium-containing emollient. RESULTS: Twenty-four mediators could quantitatively be determined. The Th2 mediators interleukin (IL)-4, IL-13, CCL2 (monocyte chemotactic protein-1), CCL22 (macrophage-derived chemokine), and CCL17 [thymus and activation-regulated chemokine (TARC)] were significantly decreased after therapy as well as IL-1ß, IL-2, IL-8 (CXCL8), IL-10, acute-phase protein serum amyloid A, C-reactive protein, and vascular adhesion molecule-1. The decrease of CCL17 and IL-8 was correlated with the decrease in disease severity in a subgroup of moderate AD individuals. CONCLUSION: Stratum corneum tape stripping offers a minimally invasive approach for studying local levels of immunomodulatory molecules in the skin. CCL17 (TARC) and IL-8 were found to be the most promising biomarkers of AD and might be useful for investigating the course of skin diseases and the effect of local therapy.

The Leser-Trélat Sign in a Patient with Gastric Adenocarcinoma.

Dear Editor, The Leser-Trélat sign is a rare paraneoplastic cutaneous marker of internal malignancy characterized by sudden eruption of multiple seborrheic keratoses (SK). It is mostly associated with gastrointestinal adenocarcinomas (gastric, colon, rectal), and less frequently with breast cancer and lymphoproliferative disorders/lymphoma (1). It can be also associated with lung, kidney, liver, and pancreas malignancy (1). Pruritus occurs in half of the patients. Lesions rarely require any treatment, as they mostly tend to resolve once management of the underlying malignancy has started (2). A 32-year-old female patient with family history of colorectal cancer presented with an acute eruption of SK. She reported that the first symptoms were the loss of appetite and intense pruritus. The brown papules appeared over a period of 2-3 months, first on her back, then on the abdomen, thorax, neck, and lasty on the extremities (Figures 1a and b.). Physical examination showed numerous brown hyperkeratotic papules and plaques on the trunk, neck, and extremities. The patient complained of night sweating, epigastric pain, and heartburn. Over the last three months, she had lost over 15 kg. The patient had experienced an episode of acute gastritis 10 years ago and had been treated for Helicobacter pylori infection 4 years ago. Laboratory results showed elevated sedimentation rate and decreased levels of hemoglobin, erythrocytes, and hematocrit. CA-19-9 and CEA levels were elevated. Gastroscopy with multiple biopsies confirmed gastric adenocarcinoma. An abdominal CT scan revealed enlarged retroperitoneal lymph nodes. SK withdrew after total gastrectomy and commencement of chemotherapy. The Leser-Thrélat sign was named after two surgeons, Edmund Leser and Ulysse Trélat, who described the eruption of cutaneous lesions in patients with cancer (3). However, the correlation between multiple SK and internal malignancy was described by Hollander in 1900 (4). Acute eruption of SK has also been reported in some other cases, such as benign tumors, pregnancy, human immunodeficiency virus infections, use of adalimumab, and others, which indicates that the Leser-Trélat sign is not highly specific (5). It is also somewhat controversial whether a sudden appearance of SK can be considered a marker for internal malignancy, since both SK and malignancies occur more frequently in the elderly population, thus allowing for a higher likelihood of coincidence (6). However, the patient in this case was young and therefore less likely to suddenly develop such a large number of SK, which are more commonly seen after the age of 50 (7). Although the pathogenesis of Leser-Thrélat sign is not fully understood, there are data suggesting an association with tumor-secreting growth factors including epidermal growth factor and transforming growth factor-alpha, both of which can stimulate the epidermal growth factor receptor (8). Sudden appearance of eruptive SK is uncommon in young patients. This specific sign highlights the importance of considering internal malignancy in the differential diagnosis of patients presenting with eruptive SK.

Hypersensitivity Reactions to Homemade Topical Preparations.

Homemade topical preparations are becoming increasingly popular due to the widespread belief that herbal and natural products are a safer and better option in the treatment of various conditions. However, homemade topical preparations can precipitate allergic and irritant reactions, depending on the herbal composition of the preparation. Hypersensitivity reactions to such preparations range from contact allergic dermatitis, contact irritant dermatitis, contact urticaria, toxic reaction, photosensitivity, and phototoxic reaction. In Europe, and especially in the Mediterranean area, medicinal herbs from the Compositae family and aromatic Mediterranean herbs are most frequently used in the formulation of topical preparations. Although plants are regarded as strong sensitizers, the number of reported cases of hypersensitivity reactions is relatively small. The problems are limitations in diagnostics due to the lack of necessary patch test substances and the danger of active sensitization during testing. Caution is required in patients prone to allergies and those with existing dermatoses, who should be advised to use registered preparations. The first step in management is cessation of exposure, followed by implementation of topical corticosteroids. Systemic corticosteroid therapy is reserved for more severe cases.

Analysis of Hexavalent Chromium in Cement Samples From Countries Within and Outside the EU: A Study From the International Contact Dermatitis Research Group.

Background: Allergic contact dermatitis (ACD) caused by hexavalent chromium (Cr(VI)) is often severe and difficult to treat. The content of Cr(VI) in cement can be reduced by, for example, addition of iron(II) sulfate. Since 2005 the content of Cr(VI) in cement is regulated in the EU Directive 2003/53/EC and must not exceed 2 ppm. Since this regulation came into force, ACD caused by cement has markedly been reduced. Objective: To investigate Cr(VI) and total chromium content in samples of cement from countries within and outside the EU. Methods: The members of the International Contact Dermatitis Research Group (ICDRG) were invited to participate in the study with the aim to collect cement samples from geographically different areas. The content of Cr(VI) in the samples was estimated by the diphenyl carbazide spot test, atomic absorption spectroscopy was used to assess the total chromium content. Results: Forty-five cement samples were analyzed, containing amounts of Cr(VI) from <0.1 to >70 ppm. Twenty-one samples contained >2 ppm Cr(VI), 24 contained less. Four of 17 samples from within the EU contained >2 ppm Cr(VI), that is, higher amounts than stipulated in the EU directive, as compared with 17 samples from countries outside the EU. Conclusion: In countries outside the EU, significantly more cement samples contained >2 ppm Cr(VI).

Coexistence of Lichen Planus Pemphigoides, Palmoplantar Keratoderma of Unna-Thost, and Atopic Dermatitis.

Lichen planus pemphigoides (LPP) is a very rare autoimmune blistering disease associated with lichenoid skin changes. Unna-Thost palmoplantar keratoderma (PKK) is a type of diffuse palmoplantar keratoderma that mostly affects the palms of the hands and soles of the feet. It usually begins in early childhood. We present a unique case of coexistence of LPP, Unna-Thost PPK, and atopic dermatitis (AD). To our knowledge, there are three reported cases of both LPP and Unna-Thost PPK and a few reports of coexistence of Unna-Thost PKK and AD.

Dowling-Degos Disease in the Anogenital Region.

Dowling-Degos disease (DDD) is a benign, rare genodermatosis (reticulate pigmented anomaly) of flexure sites with autosomal dominant inheritance (1,2).The disease is caused by a loss-of-function mutation of keratin 5 (KRT5) present on the chromosome 12q gene (3). It usually affects the younger population, most commonly 20-30 years of age, with some patients being older and with a predominance in the female population (4). The disease is characterized by formation of dark, hyperpigmented macules which are confined to the flexure sites, most commonly over the axillae, groin area, and neck, along with scattered, comedo-like lesions and pitted acneiform scars (3,5).The diagnosis is established based on clinical and histopathological correlation. We report the case of a 39-year-old patient who presented with a dark brown discoloration of the skin in the area of vulva, perineum, and perianal region (Figure 1) with occasional itching sensation that had suddenly appeared a year before presentation at our Department. Additionally, sparce brown macules were found in the left axillary region that had appeared a few months earlier. Histopathology of the skin showed fine and irregular elongation of the interpapillary cones with hyperpigmentation. Based on her clinical presentation and histopathology, the diagnosis of DDD was established. The patient was unsuccessfully treated with adapalene gel and refused the recommended oral retinoid therapy, as well as laser therapy. Dowling-Degos disease can present as an isolated disease or can be linked to other clinical entities. Usually, it presents with flat macules which are 3-5 mm in diameter and can vary in color from light brown to black (6). Furthermore, the disease is almost always asymptomatic, but pruritus has been reported in some cases (6), as observed in our patient. Even though DDD is primary a disease of the flexures, there have been reports of patients that have presented with hyperpigmented macules on the dorsum of the hands and feet (7). The affected areas in our patient were the anogenital region and left axillary region, and even though this combination of areas is rather uncommon, to our knowledge two similar cases have been reported in the literature (6,8). The most notable histopathological findings of DDD are elongation of rete ridges of the epidermis as well as hyperpigmentation, usually found in the lower third of the elongated rete ridges (6); both of those features were present in the skin biopsy specimen of our patient. Both the clinical picture and pathohistological findings are crucial for the diagnosis of DDD, and we can conclude that the findings of our patient were consistent with DDD. There are a number of closely related entities to Dowling-Degos disease: Galli-Galli disease (GGD), reticulate acropigmentation of Kitamura (RAPK), Haber disease, and symmetrical acropigmentation of Dohi. Galli-Galli disease has an almost identical clinical presentation, the only difference between those two entities being the presence of acantholysis on biopsy in GGD (9). RAPK presents with hyperpigmentation on the dorsum on the hands and feet, and that pattern has been observed in some patients with DDD as well as GGD (6,7,10-12). However, it differs from DDD in the presence of palmar and plantar pits and slight depression of pigmented lesions (6). Haber disease also has a very similar clinical presentation to DDD, with the presence of dark papules on flexure sites; however, central facial telangiectatic erythema was observed only in Haber disease (13). The clinical features of symmetrical acropigmentation of Dohi are the presence of hyperpigmented macules on the dorsum of the hands and feet, but intermingled areas of hypopigmented macules can also be observed, and the onset of the disease is earlier (infancy and early childhood) when compared with DDD (6,14). There are no successful treatments for DDD. Topical steroids may reduce the itching. Hydroxyquinone, a topical retinoid (adapalene gel), can be used for fading the pigmentation, but there rapid recurrence was reported when treatment was ceased (15). Systemic retinoids have also been unsuccessful. Er:YAG laser treatment has been reported to be effective, but only in a few cases (6,16,17). The goal of this paper was to present the case of a patient with DDD on the vulva, perineum, and perianal region as well as to describe the relationship of DDD with other members of the hyperpigmentative disease family.