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.

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.

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.

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).

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.

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.

The Association Between the Severity of Psoriasis and Obesity Based on the Analysis of Visceral Fat Index and Serum Levels of Tumor Necrosis Factor-α, Interleukin-6, and Resistin.

Aim of this study was to investigate the relationship between the severity of psoriasis and obesity based on the analysis of the visceral fat index and serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and resistin. The study included 50 patients with psoriasis and 30 subjects in the control group. The measured parameters were height, weight, waist circumference, visceral fat index, and serum levels of TNF-α, IL-6, and resistin. The severity of the disease was evaluated using the psoriasis area and severity index (PASI). Visceral fat index was measured using the method of bioelectrical impedance analysis. Serum levels of TNF-α, IL-6, and resistin were correlated with visceral fat index, and the relationship of all these parameters with psoriasis severity was also analyzed. Patients with psoriasis have a significantly higher body mass index, waist circumference, and visceral fat index compared with the control group. Elevated serum levels of TNF-α, IL-6, and resistin, as well as a correlation with psoriasis severity and visceral fat index was also found in the patient group. Visceral fat index was a better indicator of the relationship between psoriasis severity and obesity than waist circumference and body mass index. We concluded that serum levels of TNF-α, IL-6, and resistin could be useful in assessing psoriasis activity and optimizing therapeutic strategies. It is suggested that visceral fat index should be evaluated in all patients with psoriasis, especially before the decision on systemic therapy.

Patch Testing With Nickel Sulfate 5.0% Traces Significantly More Contact Allergy Than 2.5%: A Prospective Study Within the International Contact Dermatitis Research Group.

BACKGROUND: Nickel allergy is the most common contact allergy, and a nickel salt is, therefore, included in most baseline patch test series. In the baseline series of the International Contact Dermatitis Research Group and the American Contact Dermatitis Society, nickel sulfate hexahydrate (NSH) in petrolatum at 2.5% is included, whereas NSH at 5.0% is included in many other baseline series, such as the European and Swedish ones. OBJECTIVE: The aim of the study is to investigate whether NSH at 5.0% detects significantly more contact allergy than NSH 2.5% when both preparations are tested simultaneously in consecutive dermatitis patients. PATIENTS AND METHODS: Two thousand two hundred eighty-seven consecutive dermatitis patients were patch tested simultaneously with NSH in petrolatum at 2.5% and 5.0%. The allergy rates were compared for all clinics individually and combined using McNemar test, 2-sided. RESULTS: Contact allergy to NSH 5.0% and 2.5% was found in 20.3% and 16.8%, respectively ( P < 0.0001). In 6 of 11 clinics, significantly more patients tested positive to the higher NSH concentration. For the 2 clinics in North America combined, significantly more patients tested positive to NSH 5.0%. CONCLUSIONS: The NSH preparation in the International Contact Dermatitis Research Group baseline patch test series should be considered to be changed from NSH 2.5% (1 mg NSH/cm 2 ) to 5.0% (2 mg NSH/cm 2 ).

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.

Allergic Contact Dermatitis, Allergic Airborne Dermatitis, and Occupational Asthma Caused by (meth)acrylates in Artificial Nails.

Allergic contact dermatitis (ACD) caused by (meth)acrylates is traditionally an occupational disease among dentists, printers, and fiberglass workers. With the use of artificial nails, cases have been reported both in nail technicians and in users. ACD caused by (meth)acrylates used in artificial nails is a relevant problem for both nail artists and consumers. We present the case of a 34-year-old woman who was working in a nail art salon for two years prior to the appearance of severe hand dermatitis, especially on her fingertips together, with frequent appearance of face dermatitis. The patient had artificial nails for the last 4 months because her nails were more prone to splitting, so she was regularly using gel to "protect" them. While she was at her workplace, she reported multiple episodes of asthma. We performed patch test to baseline series, acrylate series, and the patient's own material. In the baseline series, the patient had positive reactions to nickel (II) sulfate (++/++/++), fragrance mix (+/+/+), and carba mix (+/+/+), 2-hydroxyethyl methacrylate (2-HEMA) (++/++/++), ethylene glycol dimethylacrylate (EGDMA) (++/++/++), hydroxyethyl acrylate (HEA) (++/++/++), and methyl methacrylate (MMA) (+/+/+). Semi-open patch test was positive to 11 of the patient's own items (10 out of 11 were made of acrylates). There has been a significant increase in the incidence of acrylate-induced ACD among nail technicians and consumers. Cases of occupational asthma (OA) induced by acrylates have been described, but respiratory sensitizations of acrylates are still insufficiently investigated. Timely detection of sensitization to acrylates is primarily necessary in order to prevent further exposure to allergens. All measures should be taken to prevent exposure to allergens.

Meatal Intraurethral Warts Successfully Treated with 5-fluorouracil Cream.

Condyloma acuminatum relatively rarely involves the urethra, and when it does it is usually only in the most distal portion of the urethra. A number of treatments have been described for urethral condylomas. These treatments are extensive and variable, comprising laser treatment, electrosurgery, cryotherapy, and topical application of cytotoxic agents such as 80% trichloroacetic acid, 5-fluorouracil cream (5-FU), podophyllin, podophyllotoxin, and imiquimod. Laser is still considered to be therapy of choice for treatment of intrauretral condylomata. We present the case of a 25-year-old male patient with meatal intraurethral warts who was successfully treated with 5-FU, after many unsuccessful treatment attempts with laser treatment, electrosurgery, cryotherapy, imiquimod, and 80% trichloroacetic acid.

Ketoprofen-induced Photoallergic Reaction.

Dear Editor, Photoallergic reactions are classic T-cell-mediated or delayed-type hypersensitivity reactions of the skin in response to a photoallergen (or a cross-reacting chemical) to which a subject was sensitized in the past (1). The immune system recognizes the changes caused by ultraviolet (UV) radiation; it produces antibodies and causes inflammation of the skin in the exposed areas (2). Common photoallergic drugs and ingredients are included in some sunscreens, aftershave lotions, antimicrobials (especially sulfonamides), non-steroidal anti-inflammatory drugs (NSAIDs), diuretics, anticonvulsants, chemotherapy drugs, fragrances, and other hygiene products (1,3,4). A 64-year-old female patient was admitted to the Department of Dermatology and Venereology with erythema and underlining edema on her left foot (Figure 1). A few weeks earlier, the patient had had a fracture of the metatarsal bones and since then she had been taking NSAIDs systemically every day to suppress pain. Five days before being admitted to our Department, the patient started applying 2.5% ketoprofen gel to her left foot twice daily and was frequently exposed to the sun. For the last twenty years, the patient had been struggling with chronic back pain and was frequently taking different NSAIDs (ibuprofen, diclofenac, etc.). The patient also suffered from essential hypertension and was regularly taking ramipril. She was advised to discontinue ketoprofen application, avoid sunlight, and apply betamethasone cream twice daily for 7 days, which lead to complete resolution of the skin lesions in a few weeks. Two months later, we performed patch and photopatch tests to baseline series and topical ketoprofen. Only the irradiated side of the body where ketoprofen-containing gel was applied showed positive reaction to ketoprofen. Photoallergic reactions manifest as eczematous, pruritic lesions, which may spread to involve other areas of the skin that were not previously exposed to the sun (4). Ketoprofen is a nonsteroidal anti-inflammatory drug composed of a benzoylphenyl propionic acid that is commonly used both topically and systemically for the treatment of musculoskeletal diseases because of its analgesic and anti-inflammatory effects and low toxicity, but it is one of the most frequent photoallergens (1,5,6). Ketoprofen-induced photosensitivity reactions usually present as photoallergic dermatitis characterized as acute dermatitis with edema, erythema, papulovesicles, blisters, or erythema exsudativum multiforme-like lesions at the application site 1 week to 1 month after the initiation of use (7). Depending on the frequency and intensity of sun exposure, ketoprofen photodermatitis may continue or reoccur up to 1 to 14 years after discontinuing the medication (6,8). Moreover, ketoprofen contaminates clothing, shoes, and bandages, and some cases of photoallergy relapses have been reported that were induced by ketoprofen-contaminated objects after they were used again in the presence of UV radiation (5,6). Due to their similar biochemical structure, patients with ketoprofen photoallergy should avoid using some drugs such as some NSAIDs (suprofen, tiaprofenic acid), antilipidemic agent (fenofibrate) and sunscreens based on benzophenones (6,9). Physicians and pharmacists should advise patients of the potential risks when topical NSAIDs are applied on the photoexposed skin.

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.

Pityriasis Rosea after COVID-19 Infection.

Dear Editor, Pityriasis rosea (PR) is a common, self-limited erythematous papulosquamous dermatosis that mainly affects young adults. It is believed to represent a delayed reaction to viral infections and is usually associated with endogenous systemic reactivation of human herpesvirus (HHV) 6 and / or 7 (1). A 46-year-old man presented to our Department with a two-week history of skin rash associated with mild pruritus. He described the appearance of an erythematous centrally scaled lesion at the right part of his abdomen, followed by the spreading of red oval mildly scaling lesions on the trunk, neck, and proximal parts of the upper extremities, which showed in the physical examination (Figure 1, a and b). He was otherwise healthy and taking no medications. Six weeks prior to the appearance of the initial skin lesion, the patient had coronavirus disease 2019 (COVID-19) infection with mild clinical presentation (fever up to 38 °C lasting for four days and mild headache) and with symptoms of post COVID-19 syndrome (excessive tiredness). He denied oropharyngeal lesions. Potassium hydroxide, syphilis, and laboratory tests were within normal limits. Within two weeks of topical betamethasone dipropionate treatment, the lesions disappeared completely. In addition to reactivation of HHV-6 or HHV-7, PR can be triggered by some drugs (like angiotensin-converting enzyme inhibitors alone or in combination with hydrochlorothiazide, sartans plus hydrochlorothiazide, allopurinol, nimesulide, and acetyl salicylic acid (2) and vaccines (such as smallpox, poliomyelitis, influenza, human papillomavirus, diphtheria, tuberculosis, hepatitis B, pneumococcus, and yellow fever vaccines) (3). There is a growing number of published cases that link PR to COVID-19 infection, with PR appearing either in the acute phase of COVID-19 or, as in our patient, in the post COVID-19 period (4-9). Unlike in our patient, oropharyngeal lesions were observed in approximately 16% of patients with typical PR (10). It has been suggested that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces reactivation of other viruses, such as HHV-6, HHV-7, varicella zoster virus, and Epstein-Barr virus (5). PR has also been reported to follow COVID-19 vaccination (11). As our patient did not receive a COVID-19 vaccine, we cannot evaluate the latter based on the present case. We speculate that PR could be a delayed skin manifestation of COVID-19 infection, triggered either by SARS-CoV-2 immediately or indirectly by the reactivation of other viruses such as HHV-6 or HHV-7. However, the etiopathogenetic mechanisms remain largely unknown and further studies are needed in order to clarify the correlation between SARS-CoV-2 and PR.

Fecal Calprotectin as a Biomarker of Food Allergy and Disease Severity in Children with Atopic Dermatitis without Gastrointestinal Symptoms.

Fecal calprotectin (FCP) is a biomarker of intestinal inflammation and has recently been proposed as a diagnostic biomarker of food allergy (FA) in children. The aim of this study was to compare FCP level in infants and children under 4 years old with 1) atopic dermatitis (AD) with food allergy (FA) and 2) children with AD and without FA with the results in healthy controls. In total, 46 infants and children (mean age 14 months ± 12) diagnosed with AD were divided into two groups: G1, children with atopic AD with FA (n=28) and G2, children with AD without FA (n=18). The control group (G3) was made up of healthy children of the same age (n=18). The median FCP was significantly higher in G1 compared with G2 (G1: median 154, IQR 416 µg/g vs G2: median 41.3, IQR 59 µg/g; P=0.0096). The median FCP in children with AD and FA was significantly higher before elimination diet in comparison with FCP after 3 months of elimination diet (median 154, IQR 416 µg/g vs median 35, IQR 23 µg/g; P=0.0039). The level of FCP was significantly positively correlated with the SCORAD score (r=0.5544, P=0.0022). Our study showed a significant difference in level of FCP in patients with AD without FA compared with patients with AD and FA. We also found a positive correlation of FCP with SCORAD score, a biomarker of AD severity. New studies are needed to investigate the role of FCP as a biomarker of FA in children with AD.

Morbihan Disease - An Old and Rare Entity Still Difficult to Treat.

Morbihan disease (MD), also known as Morbihan syndrome, "solid persistent facial edema and erythema", "rosacea lymphedema", and "solid facial edema in acne", is a rare and often unrecognizable entity, that presents with a slow occurrence of persistent lymphoedema of the upper two-thirds of the face (1,2). A 30-year-old woman presented to our Department with persistent, asymptomatic face edema and erythema lasting for 18 months. She was previously treated for rosacea with doxycycline (100 mg/day for four months) without improvement. Dermatological examination revealed erythematous, nonpitting, solid edema located on the mid-forehead, nose, and cheeks with sparse erythematous papules and pustules on the entire face including the chin and comedones, papules, and pustules on the back (Figure 1 and Figure 2). She was otherwise healthy and was not taking any medication. Laboratory tests with immunological tests and Quantiferon test together with MRI of the orbits, chest X-ray, chest high-resolution computed tomography, cranial X-ray, and abdominal ultrasound were all within normal limits. Histopathology revealed dermal edema, perivascular and peri-adnexal lymphohistiocytic infiltrate, and sebaceous gland hyperplasia. Based on the typical clinical picture, histopathological findings, and the exclusion of several differentials the diagnosis of MD was established. The patient was treated with oral isotretinoin (20 mg/day for eight months) without regression of solid edema and erythema on the face but with complete regression of acne on the trunk. She was started on oral corticosteroids (prednisolone, 20 mg/day for two months followed by reduction of the dose over three months), again with only slight short transient improvement and rapid relapse of facial erythema and edema. The patient refused any other suggested treatment. We treated our patient for a total 2 years and followed up for 5 years. The pathogenesis of MD is still unknown. It is considered a clinical variety or a complication of rosacea or acne which does not tend to regress spontaneously. It is believed that chronic inflammation in patients with MD is due to acne or rosacea causing structural damage to blood and lymph vessels (1,3,4). However, cases of MD without previous history of rosacea and acne have been reported supporting the distinct disease theory (3,4). Edema and erythema are localized on the upper half of the face affecting the forehead, glabella, eyelids, nose, and cheeks. Although the symptoms may come and go, MD usually does not improve without treatment (5). Several therapeutic options have been reported, although there is no established standard treatment for MD. Reported therapy includes short-term oral isotretinoin (0.5 mg/kg/day), long-term oral isotretinoin (40-80 mg/day, 10-24 months), long-term doxycycline, combination of systemic corticosteroids and antibiotic (prednisolone 20 mg/day for 2 weeks and doxycycline 200 mg/day for 12 weeks), slow-releasing doxycycline monohydrate (40 mg/day for 6 months), long-term minocycline (50 mg/day for 4 months), and a combination of both oral retinoid and ketotifen (isotretinoin 0.7 mg/kg/day for 4 months, ketotifen 2 mg/day for 4 months) (1,2,6,8). The disease is frequently recalcitrant to therapy, and only several cases of successfully treated patients with MD have been reported (1,2,4, 6-8). We presented a patient with characteristic features of MD, which is a persistent, cosmetically disturbing condition, unfortunately mostly refractory to therapeutic measures.

Unusual Case of Granuloma Annulare Associated with Diabetes Mellitus.

Dear Editor, Granuloma annulare (GA) is an asymptomatic, chronic, and relatively common granulomatous skin condition which presents with annular papules usually slowly progressing into plaques on the extremities and the trunk. It usually presents with non-scaly, erythematous, annular plaques on the distal extremity (1,2). The pathogenesis of GA is still unknown, although a variety of possible factors contributing the disease have been reported, including drugs (3), insect bites, sun exposure, trauma, vaccinations, and viral infections (e.g. hepatitis B, hepatitis C, HIV, Epstein-Barr virus) (1). Several cases in which GA developed on residual skin changes from herpes zoster have also been reported (4). A 47-year-old woman presented with erythematous-livid plaques on the dorsa of her hands and linear and circular lesions on her neck, gradually spreading for the last 4 months prior to admission at our Department (Figure 1a and Figure 1b). She reported excessive thirst and sweating in the last 30 days, but did not consider it significant since it was summer. The patient was otherwise healthy and was not taking any medications. Mycological swabs taken from the dorsal parts of both hands and the neck were negative. Biopsy of the skin changes was consistent with GA, showing palisading granulomatous inflammation which surrounded degenerated collagen within the dermis. A routine laboratory check revealed increased levels of glucose (23 mmol/L) and HgbA1C, while lipid and thyroid hormone levels were normal. Fasting blood sugar lever was 17 mmol/L. Therapy with topical corticosteroid (betamethasone cream) for skin lesions was initiated and applied two times daily for 2 weeks. The patient was immediately referred to an endocrinologist and insulin therapy was initiated due to diabetes mellitus. Complete remission of the skin changes was observed on the follow-up visit after 3 months. There are many clinical variants of GA such as localized, generalized, disseminated, subcutaneous, arcuate dermal erythema, and perforating GA (1). The localized form of GA is most common with annular plaques on the distal extremities. In addition to the typical lesions on the dorsal side of both hands, our patient also presented with atypical, circular lesions around her neck. The relationship between GA and systemic diseases such as diabetes mellitus, thyroid disorders, dyslipidemia, and malignancies remains unclear (5). It is also uncertain whether genetic factors influence susceptibility to GA. Familial cases have been documented, but studies investigating the association between the disease and human leukocyte antigen (HLA) genes have yielded inconsistent results (6). Increased frequency of HLA-B35 in patients with the generalized form has been reported in a few studies (7). GA mostly affects children and young adults, mostly women. Many cases of GA resolve spontaneously within 2 years, but relapses occur in many patients. Treatment is divided into localized skin therapies and systemic therapies (1). High potency topical corticosteroids along with intralesional corticosteroids are the most common localized treatments (8). Systemic therapy includes corticosteroids, chloroquine, dapsone, and isotretinoin (1,9). Cryotherapy and UV-therapy can also be used, although with limited efficacy (10). GA is a common idiopathic disorder of the dermis and subcutaneous tissue that can be associated with a variety of underlying conditions such as diabetes mellitus. The relationship between GA and diabetes mellitus is still unknown. Since skin lesions preceded the diagnosis of DM in our patient and complete remission of skin changes occurred with induction of insulin therapy, it is important to perform routine laboratory test in every patient.

Contact Sensitivity in Patients with Atopic Dermatitis.

Atopic dermatitis (AD) is a common chronic and relapsing, non-contagious inflammatory skin disorder, characterized by skin barrier impairment and baseline immune irregularities. The literature on the relationship between AD and cutaneous delayed-type hypersensitivity is inconclusive. There is an ongoing debate whether contact sensibility (CS) is found more or less often among patients with AD. Aim of the study was to evaluate the incidence of contact sensitivity (positive patch test reactions) in patients with and without AD. We patch tested a total of 2143 patients (563 men and 1580 women). There were 226 patients with history of AD; 61 (27%) men and 165 (73%) women. The patient group without AD consisted of 1917 patients, 502 (26%) male and 1415 (74%) female patients, who were referred to our Department with clinical suspicion of allergic contact dermatitis (ACD). A patch test was performed with the baseline series, and readings were performed on days D2, D3, and D7. Among patients with AD, 109 (48.2%) had a positive patch test reaction to at least one allergen, whereas 1094 (57.1%) patients with no history of AD had a positive patch test reaction. The most common positive allergens in patients with AD were nickel (II) sulfate (13.3%), thimerosal (12.4%), cobalt (II) chloride (11.5%), methylisothiazolinone (MI) (8.4%), fragrance mix I (6.6%), potassium dichromate (5.3%), methyldibromo glutaronitrile (4.0%), and carba mix (4.0%). The results of our study agree with previous findings that there is no significant difference in prevalence of CS between the atopic and nonatopic populations.