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.

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.

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 ).

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.

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.

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.

Oral and Vulvar Lichen Sclerosus.

Lichen sclerosus (LS) is a chronic, inflammatory, mucocutaneous disorder of genital and extragenital skin (1). Simultaneous involvement of the oral mucosa is extremely rare, but it may be the only affected area (2). A 55-year-old woman was referred to the Department of Oral Medicine, School of Dental Medicine University of Zagreb due to whitish lesions on the right ventrolateral part of the tongue and buccal mucosa with desquamative gingivitis (Figure 1, a-c). The lesions were asymptomatic but indurated on palpation. Histology was conclusive for oral lichen sclerosus (OLS). The lesions on gingiva were successfully treated with betamethasone ointment, three times a day for two weeks. One year earlier, she had been referred to the Department of Dermatology and Venereology with progressive pruritus and dyspareunia, white patches, obliteration of the labia minora, and stenosis of the introitus (Figure 2). Histology was conclusive for vulvar LS (Figure 3, a and b). She was successfully treated for 5 months with clobetasol propionate 0.05% ointment. The patient was taking levothyroxine to treat hypothyroidism associated with Hashimoto's thyroiditis and was otherwise healthy. Oral LS is clinically characterized by the appearance of white macules, papules, or plaques mostly appearing on labial mucosa but also on buccal, palate mucosa and on the lower lip (2,3). On the genitals, it typically manifests as atrophic white plaques, which may be accompanied by purpura or fissuring (1). While vulvar LS is often associated with pruritus, dyspareunia, and dysuria, OLS is often asymptomatic, although pain, soreness, pruritus, and tightness when opening the mouth can be present (1,2). Oral manifestations of LS, as well as association of anogenital and oral LS, are rarely reported in the literature (4-6). Tomo et al. searched the Medline database for papers reporting oral LS cases with histological diagnosis confirmation from 1957 to 2016 and found only 34 cases of oral LS with histopathologic confirmation of the diagnosis (4). Kakko et al. reported 39 histologically proven cases of OLS (2). Attilli et al. (5) reviewed the clinical and histologic features of 72 cases of LS with oral/genital involvement. They reported that LS was diagnosed with exclusive genital lesions in 45, exclusive lip involvement in 20, and orogenital involvement in only 7 cases (5). Some believe that many cases of clinically diagnosed lichen planus may actually be LS and that isolated oral mucosal LS may not be as rare as is generally thought (2). While vulvar LS can occur at any age with increasing incidence with age, the median age of patients with OLS was 34 years and most of the patients were female (1,2,5). Due to the small number of patients in the literature, treatment recommendations for OLS are not available. In case of symptomatic oral lesions, topical or intralesional corticosteroids are considered to be the first-line treatment (2). First-line treatment for anogenital LS is a potent to very potent topical corticosteroid ointment, and second-line therapies include topical calcineurin inhibitors 1% pimecrolimus and 0.1% and 0.03% tacrolimus (1). For treatment-resistant genital LS, oral retinoids, methotrexate, and possibly local steroid injections for single lesions are mainly applicable for women (1). There is limited evidence for systemic treatments for both conditions. If it is not treated, genital LS is associated with a greater degree of scarring and an elevated risk of progression to squamous cell cancer; however, malignant transformation of OLS has not been reported (1-6). Due to the very rare presentation in the oral cavity, it is important to notice these lesions during a dental exam.

Localized Perforating Granuloma Annulare.

Perforating granuloma annulare (PGA) is a rare type of granulomatous skin disease. The etiology and pathogenesis of PGA are still unknown. Diagnosis and treatment of PGA is complex and challenging. We present the case of a 31-year-old male patient with a localized form of PGA successfully treated with topical steroids.

Coexistence of Anogenital Psoriasis and Genital Warts - Is There an Optimal Treatment?

The prevalence of psoriasis is 2% of the world's population (1). Inverse psoriasis is characterized by the development of erythematous shiny plaques at intertriginous areas of the body. The prevalence of only anogenital involvement appears to be low, but involvement of the anogenital area together with other areas is found in up to 45% of patients with psoriasis (2). A 21-year-old female student with a 3-month history of mild psoriasis (erythematosquamous plaque on the elbows and nail pitting on the nails of the hand) was referred to our Department. One month earlier, suddenly appearance of erythematous, smooth, clearly demarcated plaques was observed on the labia majora, the mons pubis, the perineal and perianal region together with a brownish hyperkeratotic papule on the pubic region (Figure 1, a-b). The patient underwent excisional biopsy at the Department of Surgery, and the pathohistological finding was unavailable to us. The elbows were treated with corticosteroid-keratolytic preparation, whereas the anogenital lesions were treated with moderately potent topical corticosteroids. In addition to anogenital erythema, on clinical examination we noticed an erythematosquamous plaque on the site of excision with a hyperkeratotic verrucous papule on the edge of the lesion (the Koebner phenomenon on the site of skin injury). In the pubic region, we noticed two hyperkeratotic papules and a few verrucous papules on labia majora. Localized dermatophyte or candida infection were excluded with a KOH test and scrapings culture. Serology for syphilis, HIV, and hepatitis were negative. Cervical Pap smear was normal. Biopsy of erythematosus lesion from the mons pubis was conclusive for psoriasis, and of the keratotic papule with the genital wart with positive HPV 6 and 11. The patient's older sister had chronic plaque psoriasis. We employed physically ablative methods like liquid nitrogen cryosurgery, electrocauterization, and curettage, applied topical agents like 0.5% podophyllotoxin solution, 20% podophyllin, and 80% trichloroacetic acid, and treated the psoriatic lesions with a short course of moderate-potency corticosteroids and tacrolimus ointment. All therapeutic attempts were ineffective for curing both diseases. Our patient either had psoriasis with sparse genital warts or exacerbation of multiple anogenital warts (Figure 2, a-b). Anogenital psoriasis is a skin disease that causes great discomfort. The disease-related quality of life is significantly reduced, especially regarding sexual behavior. Therapy for either anogenital psoriasis or genital warts is not entirely satisfactory. Many topical agents suitable for use on the psoriatic lesions on the body, such as coal tar, anthralin, vitamin D derivatives or retinoids, may be too irritating in the anogenital region. The most useful therapy for treatment of anogenital psoriasis are moderately potent topical corticosteroids and topical tacrolimus or pimecrolimus (1). However, corticosteroid-induced atrophy is possible in intertriginous sites. The Koebner phenomenon isomorphic response is the appearance of new skin lesions on areas of cutaneous injury in otherwise healthy skin (3). About 25% of patients with psoriasis have elicitation of psoriatic lesions by injury to the skin (4). Other than in patients with psoriasis, the Koebner phenomenon can be found in other skin diseases like vitiligo, lichen planus, lichen nitidus, pityriasis rubra pilaris, flat warts, and keratosis follicularis (Darier disease) (5). According to Eyre at al., about 67% patients with psoriasis (4) present with clearing of psoriatic lesions following skin injury (positive "reverse" Koebner reaction) (4). There is no single treatment for genital warts that is 100% effective, and different types of treatment are very often combined. Accepted methods of treatment involve chemical and physical destruction or removal (6). Since psoriasis koebnerizes, any destructive technique may exacerbate the psoriasis. Coexistence of anogenital psoriasis and HPV presents a huge therapeutic problem because a therapy for psoriasis such as corticosteroids can provoke appearance and/or reappearance of HPV infection, while some therapies for anogenital warts, like cryotherapy, curettage, laser ablation, electrosurgery, or surgery can provoke the appearance and/or reappearance of psoriatic infection due to the Koebner phenomenon.

Coexistence of genital lichen sclerosus and genital warts.

Lichen sclerosus (LS) is a chronic, inflammatory, mucocutaneous disorder of the genital and extragenital skin. Anogenital warts are benign proliferative lesions caused by human papillomavirus (HPV), which is found in > 95% of lesions. We present two cases of the coexistence of LS and genital warts: one patient with and one without a previous history of genital warts. According to our knowledge and a literature search, only a few cases of the coexistence of LS and genital warts have been reported.

Prolonged Treatment of Eosinophilic Erythema Annulare with Chloroquine.

Dear Editor,Eosinophilic annular erythema (EAE) is a rare figurate dermatitis of unknown etiology with prominent tissue eosinophilia. A 59-year-old male patient presented with a one-month history of itchy, polycyclic, annular, and partially serpiginous lesions involving the back, the gluteal region, and the extremities (Figure 1, a, b). There was no medical history of drug intake. High potency local steroids and antihistamines were prescribed, but without adequate therapeutic results. Extensive laboratory work-up including serological infectious disease testing was performed and was within normal ranges. Histopathological examination of a biopsy taken from a lesion on the gluteus showed perivascular lymphocytic infiltrate around superficial and deep vascular plexus with admixture of eosinophils that was found interstitially (Figure 2, a,b) and within the lobules of subcutaneous fat. The overlying epidermis was unremarkable. There were no signs of flame figures and granulomatous inflammation. Based on the clinical and histopathological findings, a diagnosis of EAE was established. The patient was given 40 mg of prednisone orally which resulted in partial improvement, but the lesions relapsed soon after the dose was tapered down to 20 mg. Chloroquine was started at a dose of 4 mg/kg daily for 10 days, then 250 mg daily for next the 10 weeks, resulting in complete clearance of all the lesions, which was sustained for over 2 years of follow-up. It is still matter of debate whether EAE is a clinical subtype of Wells syndrome (WS) presenting with an annular or figurate pattern or is a distinct entity. In recently published paper, El-Khalawany et al. argued that EAE is a peculiar clinical variant of WS, because flames figures, blood and tissue eosinophilia, and granulomatous infiltrate can be observed in well-developed and long-standing lesions (1). The etiology of EAE is still unknown, although it has been suggested that it occurs as a result of a hypersensitivity reaction to an unidentified allergen (2). EAE has been associated with Helicobacter pylori, Borrelia burgdorferi, and hepatitis C virus infection, diabetes mellitus, chronic kidney disease, thymoma, autoimmune pancreatitis, autoimmune hypothyroidism, and internal malignances (clear cell renal carcinoma, metastatic prostate adenocarcinoma) (3,4). Clinically, EAE is characterized by asymptomatic or mildly pruritic urticarial papules and plaques in annular configuration, mainly on the trunk and proximal extremities (5). Histologically, as in our patient, EAE is characterized by the appearance of a superficial and deep perivascular inflammatory infiltrate composed of lymphocytes and abundant eosinophils and absence of epidermal change (5). There is no standard treatment for EAE. Systemic steroids and antimalarials are the usual first-line options (5). Other treatment options include dapsone, indomethacin, cyclosporine, and UVB therapy (1,3,5). Response to antimalarials is usually observed within the first 2-4 weeks (2). However, as in our case, it may take several weeks for patients to respond to antimalarial treatment, and complete regression may even take longer (3). We believe that EAE should be treated with antimalarials over a longer time period in order to avoid frequent relapses.

Autoimmune Progesterone Dermatitis Diagnosed by Lymphocyte Transformation Test and Progesterone Provocation Test.

Autoimmune progesterone dermatitis (APD) is rare autoimmune response to endogenous progesterone or to earlier exposure to exogenous progesterone (1). Skin lesions typically occur due to increases in progesterone during the luteal phase of the menstrual cycle (2). A-31-year-old mother of two children presented to our Department with a 5-year history of pruritic and painful erythematosus macules, papules, and patches on her neck, pectoral region, and face, which appeared 2-3 days before the onset of menses and gradually resolved 7-10 days later (Figure 1). The lesions first appeared 10 months after her second pregnancy and a few months after she had started using oral contraceptive pills (OCP) containing gestodene combined with ethinyloestradiol. A few months before presenting to us, the lesions had started spreading on her forearms, elbows, and pretibial areas. Since one year prior to our visit she had complained of occasional urticaria with angioedema one week prior to menses, which resolved after menses. The lesions were accompanied by malaise, headache, and fatigue. The patient was asymptomatic between the outbreaks. She reported that she had been using various local corticosteroids, peroral antihistamines, and prednisone for the treatment of her skin lesions, but this treatment had not improved her symptoms. She suffered from mild seasonal rhinoconjunctivitis. We performed multiple laboratory tests that were unremarkable. Histopathological examination of a biopsy taken from a lesion on the neck showed epidermal hyperplasia and nonspecific mild dermal inflammation. Since progesterone was not available in aqueous solution in our country, we did not perform an intradermal test, but we performed a lymphocyte transformation test (LTT) to medroxyprogesterone and estradiol. The patient's lymphocytes showed markedly enhanced proliferation to medroxyprogesterone in vitro, while being negative to estradiol. We had performed control LTT in 10 healthy controls and 10 patients with atopy, and such hyperactivity was not observed in any of them. We performed an oral provocation test with OCP containing gestodene combined with ethinyloestradiol. Two days after commencing treatment, the patient developed widespread dermatitis (Figure 2) with nausea, malaise, and angioedema. The patient was informed about treatment options and possible side-effects. She started with OCP with the lowest amount of progesterone, containing ethinyloestradiol and dropirenone for treatment of APD, but terminated treatment after the second cycle due to a worsening of the skin lesions and urticaria accompanied with angioedema. At the time of writing, our patient continues to have premenstrual flares. The typical symptoms of APD are skin lesions such as eczema, erythema multiforme, prurigo, stomatitis, papulopustular lesions, folliculitis, urticaria, angioedema, and rarely anaphylaxis (2) that develop 3-10 days before and subside 1-2 days after menses, with recurrent cyclic aggravation (1,3,4). Frequently, patients have a history of exogenous progesterone intake (1,5,6), as in our patient, which could have resulted in antibody formation. The diagnosis of APD is established by an appropriate clinical history (premenstrual flare of skin lesions), a progesterone intradermal test, an intramuscular (7), oral (8), or intravaginal (1, 6) progesterone challenge test, and circulating antibodies to progesterone. Progesterone testing has not been standardized. Most of the sex hormones are not suitable for testing since they contain an oily component that can produce an irritant test reaction. Gestodene, which was used for the oral provocation test in our patient, is a potent progesterone (9). The LTT shows reactions to circulating lymphocytes and reflects immune reactions within the body. The goal of treatment is suppression of ovulation. Currently, the first-line choice of therapy is a combination oral contraceptive (3). We believe that OCP have a limited effect because all of them contain a progesterone component. If this treatment is ineffective, patients have been treated with danazol, gonadotropin releasing hormone analogs (3,4,6), conjugated estrogens (7), tamoxifen, oophorectomy (8), and progestogen desensitization (10) with varying success.

Genital Herpes Zoster as Possible Indicator of HIV Infection.

Herpes zoster (HZ) is an acute, cutaneous viral infection caused by the reactivation of varicella-zoster virus (VZV) (1). It is a frequent medical condition with an incidence rate of 2-3 cases per 1000 person/years in the general population and 7-10 cases per 1000 person/years after the age of 50 (1,2). Risk factors and triggers for reactivation of HZV have not yet been determined precisely, but are likely to include malignancies, immune deficiencies, solid organ and bone marrow transplant recipients, autoimmune diseases, psychological conditions, emotional stress, human immunodeficiency virus (HIV) infection, and other patients receiving immunosuppressive therapies (1,3). A 24-year-old IV drug user presented with grouped clusters of vesicles and erosions on an erythematous, edematous base distributed on the left side of the penile shaft and the left infraumbilical region (Figure 1, a and b), with regional lymphadenopathy. He had prodromal symptoms of pain, dysesthesia and burning a few days prior to the appearance of the skin lesion. The patient reported unprotected sexual contacts a few months before the eruptions. The unilateral distribution was highly suggestive of herpes zoster. A Tzanck smear was performed by obtaining scrapings from the base of a fresh vesicular lesion after it had been unroofed; it showed the characteristic presence of multinucleated giant cells that suggested herpes infection. Polymerase chain reaction (PCR) analysis of vesicular fluid yielded positive results for VZV. A 7-day course of acyclovir (800 mg 5 times a day) was initiated. The patient reported marked improvement on the second day of antiviral therapy. The course was uncomplicated, and the lesions healed without postherpetic neuralgia. Serologic tests for syphilis (VDRL/RPR and TPHA) and hepatitis C and B serologic tests were negative, but HIV test (enzyme immunoassays (EIA) for HIV-1 and HIV-2 antibodies were positive, which was later confirmed with Western blot (WB) tests. Because of the positive HIV test, the patient was referred to the Clinic for Infectious Diseases for further treatment. Herpes zoster is painful vesicular skin eruption with unilateral dermatomal involvement, usually with a severe impact on the quality of life in affected patients (1). The risk for developing HZ during a lifetime in patients exposed to VZV infection is 10-30% (4). However, the risk is higher in immunocompromised patients, particularly in cancer patients and HIV-positive patients (1,5,6). HZ is seen approximately 7 times more frequent in patients with HIV infection (5). Reactivated VZV infection may occur at any stage of HIV infection and may be the first clinical evidence of HIV infection. The development of HZ in immunocompromised individuals can be explain by decline in cell-mediated immunity and CD4 count (6). HZ predominantly affects the thoracic region, followed by the head, cervical, and lumbar regions (1). Sacral dermatomes are involved in only up to 2% of cases (1). HZ involving the penis is rarely reported, with only few case reports in the literature (3,7-9). Birch et al. compared VZV and herpes simplex virus (HSV) in specimens obtained from the genital lesions of adults presenting with presumed genital herpes infection (10). They found VZV in nearly 3% of virus-positive genital specimens, which demonstrates that this virus needs to be considered in the differential diagnosis of genital herpetic lesions (10) and that it is possible that genital HZ infection is underdiagnosed. Tzanck smear is a rapid and inexpensive method, but it cannot differentiate VZV from HSV. Genital HZ could be mistaken for zosteriform HSV infection, so a PCR test should be performed to confirm the underlying diagnosis (1). Genital forms of HZ are rare and sometimes clinically difficult to diagnose, especially when the typical zosteriform distribution is lacking; PCR testing is therefore suggested. HZ is considered a possible HIV indicator; an HIV test should therefore be performed. According to our knowledge and literature search, this is the first case report of penile HZ in an HIV-positive patient.

A Giant Basal Cell Carcinoma Misdiagnosed and Mistreated as a Chronic Venous Ulcer.

Basal cell carcinoma (BCC) is the most common cutaneous malignancy. Giant BCCs are quite rare. They can cause extensive local invasion, disfigurement, and metastasis. We present a case of a 58-year-old woman with an unrecognized and inadequately treated ulcerated giant BCC sized 12.5 × 10.0 cm that occurred on her left lower leg without any sign of metastasis. Neglect and inadequate treatment of the primary lesion are the most important contributing factors responsible for size in giant BCC.

Treatment of anogenital warts in an 18-month-old girl with 5% imiquimod cream.

Possible modes of transmission of the human papilloma virus (HPV) in children include perinatal transmission, sexual transmission, or extragenital contact. Conventional treatment options with chemical and physical destruction methods can be difficult and painful and often require general anesthesia. Imiquimod is a topically active immunomodulatory agent that has been shown to successfully treat pediatric anogenital warts. We report on a case of extensive anogenital warts in a 18-month-old girl who was successfully treated with topical 5% imiquimod cream.