Acta Dermatovenerologica Croatica最新文献

Dear Editor, Linear immunoglobulin (Ig) A bullous dermatosis (LABD), one subtype of subepidermal autoimmune bullous skin diseases (AIBDs), is characterized by linear deposit of only IgA along the basement membrane zone (BMZ) on direct immunofluorescence (DIF) (1,2). Patients showing linear deposits of both IgA and IgG are diagnosed with linear IgA/IgG bullous dermatosis (LAGBD) (3,4). Dermatitis herpetiformis (DH) is another type of subepidermal AIBD characterized by clinically pruritic erythematous skin lesions with vesicles on the elbows, knees, and buttocks with granular IgA deposits of IgA by DIF (5). In this study, we report a Japanese case of a patient who showed possible concurrence of DH and LAGBD based on clinical, histological, and immunological findings. A 72-year-old Japanese man who had a past history of dyslipidemia and resected lung cancer but was not taking any medicines, presented with a one-year history of blistering skin lesions. Physical examination revealed erythemas and peripherally arranged vesicles and erosions on the bilateral elbows, knees, and the buttock (Figure 1, a-c). Mucous membranes were not involved. The results of all laboratory tests were within normal ranges, except for increased serum IgA level 351 mg/dL (normal ranges; 46-260 mg/dL). Skin biopsy histopathologically showed subepidermal blisters infiltrated with neutrophils and eosinophils (Figure 1, d). DIF showed deposits of IgG, IgA, and complement component 3 along the BMZ mainly in granular but partially in a linear pattern (Figure 1, e-g). Circulating IgG (Figure 1, h) and IgA (Figure 1, i) autoantibodies were not detected by indirect immunofluorescence (IIF) of normal skin, however, circulating IgA (Figure 1, j) but not IgG (Figure 1, k) antibodies were bound to both the epidermal and dermal sides by IIF of 1M NaCl-split normal skin. Commercially available enzyme-linked immunosorbent assays (ELISAs) for BP180 NC16a domain, BP230, and type Vll collagen (MBL, Nagoya, Japan), showed negative results for both IgG and IgA antibodies. IgG in-house ELISA for full length BP180 was also negative. IgG and IgA immunoblotting analyses of different antigen sources, including normal human epidermal and dermal extracts, recombinant proteins of NC16a, and C-terminal domains of BP180 region, BP230, purified laminin 332, and concentrated culture supernatant of HaCaT cells for LAD-1, were all negative. IgA ELISAs of tissue- and epidermal-transglutaminases were negative (1.92 AU/mL and 20.98 AU/mL, respectively; normal range <22.0 AU/mL). The patient was successfully treated with only topical corticosteroids with occasional mild local relapses. Japanese DH is different from European DH in some respects, i.e., DH is very rare in Japan due to genetic/HLA difference, absence of celiac disease, and frequent fibrillar IgA deposition in DIF. Therefore, we believe that this case is interesting as a rare Japanese DH case with complicated conditions. The clinical and immunoch

Mucous membrane pemphigoid (MMP), previously called cicatricial pemphigoid, is a rare subepidermal immunobullous disorder that primarily affects the mucous membranes (1,2). MMP is divided into two major subtypes, anti-BP180-type MMP and anti-laminin-332 (previously called laminin 5 or epiligrin) MMP. Anti-laminin-332 MMP is known to be associated with malignant tumors (3), which may cause overexpression of autoantibodies and induce autoimmunity to laminin-332 (4). MMP primarily affects the mucous membranes, and widespread skin lesions are rare. In MMP, circumscribed skin lesions have been previously reported as occurring on the head, neck, and upper trunk (5). We report a case of anti-laminin-332 MMP presenting with symmetrical skin lesions characteristic of MMP on the weight-bearing areas of the gluteal region. A 66-year-old Japanese man presented with a month-long history of multiple erosions and blisters on the mucous membranes and skin, with conjunctival hyperemia, nasal obstruction, oral pain, and hoarseness of voice. Three days before the first visit, he was diagnosed with gastric cancer with liver metastasis by gastrointestinal endoscopy and abdominal ultrasound examination for tarry stool. Physical examination demonstrated erosions and tense bullae on the conjunctivae, tongue, and lips (Figure 1, a,b), as well as erosive erythematous skin lesions on the nape, right index finger, both legs, and symmetric lesions on the gluteal region (Figure 1, c). His body weight was 86 kg. Laboratory examinations showed slight liver dysfunction and elevation of C-reactive protein levels. Histopathologic examination of the skin lesions demonstrated subepidermal blisters with lymphocytic and eosinophilic infiltrates (Figure 1, d,e). Direct immunofluorescence (IF) revealed linear deposits of IgG and C3, but not IgA, along the basement membrane zone (BMZ) (Figure 1, f,g). An IgG subclass study showed IgG1 and IgG4 deposits. Indirect IF on normal human skin revealed weak positivity for IgA anti-keratinocyte cell surface antibodies and IgG anti-BMZ antibodies, which were bound to the dermal side of 1 mol/L NaCl-split skin (Figure 1, h). IgG immunoblot analyses of both normal human epidermal and dermal extracts showed negative results (including BP230, BP180, 290 kDa type VII collagen, and 200 kDa laminin-γ1). Immunoprecipitation using radio-labeled cultured keratinocyte lysate demonstrated positive reactivity with laminin-332 (Figure 1, i). We established the diagnosis of anti-laminin-332 MMP. We started treatment with oral minocycline (200 mg/day) and niacinamide (900 mg/day) with topical corticosteroids without any effect after 2 weeks of therapy. Administration of oral prednisolone (40 mg/day) with topical corticosteroids and alprostadil ointment on the skin lesions, as well as beclometasone dipropionate powder on the oral lesions resulted in significant improvement of mucocutaneous lesions within 10 days. Although the gastric cancer and liver metasta

Although nevi are frequently encountered in the acral region, very limited studies have reported their prevalence in specific populations. We aimed to determine the prevalence of acral nevi, their dermoscopic patterns, and evaluate patient awareness in a Turkish population. We prospectively examined 2644 patients admitted to the outpatient dermatology clinics between October 2016 and October 2017. The characteristics of the detected acral nevi and dermatoscopic images were recorded. A questionnaire of demographic characteristics was completed from all patients. Two hundred six of the 2644 patients had at least one acral nevus. Two hundred sixty nevi were examined. The general prevalence of acral nevi was 7.8%. Women were more likely to have acral nevi than men (8.7% vs. 6.3%; P=0.028). Moreover, darker-skinned patients were also had significantly more acral nevi (8.6% in skin type III-IV vs. 6.0% in skin type I-II; P<0.001). The prevalence of acral nevi was 9.4% before the age of 20, 9.5% in patients aged 20-40 years, and 4.6% after the age of 40. In addition, 51.5% of all nevi exhibited a parallel furrow, 13.5% were lattice-like, and 7.7% had a homogeneous pattern. The overall nevus awareness rate was 73.8% and was significantly higher in women at 78.3%. Our study is the first large-scale study of that showed the prevalence of acral nevi in Turkey. According to our study, the prevalence of acral nevi was higher in patients with female sex and darker skin type. We also found that the prevalence of acral nevi decreased over 40 years of age. The general awareness of nevi was higher in women.

Flagellate dermatitis is a rare cutaneous manifestation in which long, striated erythematous lesion appear on the patient's skin. It is most frequently associated with bleomycin treatment or Shiitake mushroom intake, but it may also be attributed to many other possible causes. Herein we present a case of striated, hyperpigmented lesions which occurred after bleomycin intake. The typical flagellate lesions appeared for the first time on the patient's back and shoulders after the first course of chemotherapy for seminoma (bleomycin, etoposide, and cisplatin). The active lesions disappeared with the discontinuation of chemotherapy. Clinicians should be aware of flagellate pattern of dermatitis which may accompany different clinical situations.

The process of melanoma metastasis can be divided into two stages of metastatic cell dissemination and proliferation. The whole process should be observed and distinguished through the variable or prism of time. The fact that melanoma metastases are detected in visceral organs at the stage when they are macroscopically visible does not imply that their onset has occurred much earlier. Additionally, it is quite obvious that the entire process is not driven by melanoma but rather only the initial stage of metastatic cell dissemination, whereas the later stage of metastatic cell proliferation is driven by other factors, firstly by mutated genes in the presence of melanoma or without it. Dissemination of metastatic cells occurs at approximately the same time in all melanomas, at MIS transition to MM, but is not immediately followed by metastatic cell proliferation; instead, some time has to elapse for a particular gene mutation to occur, and this timing varies among melanomas. Following dissemination of metastatic cells to visceral organs, they remain inactive, and in this period the presence of melanoma is not necessary anymore for metastatic cell proliferation, as they are waiting for a signal to start multiplying. This is clearly discernible from the fact that melanoma is today detected and removed frequently and early, but visible metastases then develop in the absence of melanoma, which may also regress spontaneously. Accordingly, MM is no longer necessary for metastasis later on. Finally, let me rephrase the title: melanoma is only responsible for initial dissemination of metastatic cells, whereas subsequent proliferation of metastatic cells is driven by other factors, most probably mutated genes.

Hereditary hemorrhagic telangiectasia (HHT) (Osler-Weber-Rendu Syndrome) is a rare autosomal dominant vascular disorder characterized by the presence of multiple arteriovenous malformations (AVMs) and recurrent bleeding episodes. The diagnosis is based on the Curacao criteria: (i) spontaneous recurrent epistaxis, (ii) mucocutaneous telangiectasia, (iii) AVMs of visceral organs, and (iv) first degree relatives with a similar condition (1). Due to a common genetic pathway and SMAD4 gene mutation, juvenile polyposis syndrome (JPS) may coexist with HHT (2). The disease burden is high in overlapping HHT/JPS, but digital clubbing may be the only physical finding. Continuous meticulous management may improve the quality of life and reduce the risk of complications. In 2000, a 15-year-old female patient was diagnosed with HHT based on epistaxis, multiple pulmonary AVMs, and a father who had similar symptoms. Other visceral AVMs were excluded. No telangiectasia was noted. On several occasions, pulmonary AVMs were managed with coil embolization (Figure 1), which successfully led to the resolution of dyspnea and cyanosis. Recurrent gastrointestinal bleedings led to severe transfusion-dependent anemia. Multiple polyps in the stomach, small intestine, and colon were repeatedly endoscopically removed, confirming the coexisting JPS. Genetic testing was not performed. Proctocolectomy was performed to prevent malignant transformation in the digestive tract. Telangiectasias are the dermatological hallmark of the HHT and occur in up to 90% of patients with the typical onset in childhood, becoming more apparent with increasing age. They are most frequently found on the face, with highest incidence on the nose, lips, tongue, and ears, followed by the fingertips, trunk, and feet; telangiectasia is recognized as the most common of the three criteria required for the diagnosis of HHT (1). Interestingly, no cutaneous telangiectasia developed in our patient during years of follow-up. However, pulmonary AVMs led to digital clubbing of her both fingers and toes (Figure 2). Digital clubbing is the focal enlargement of the connective tissue in the terminal phalanges, consequently changing the shape of nails, which become abnormally curved and shiny. It is associated with various infectious, neoplastic, inflammatory, and vascular conditions (3). Despite its well-known prevalence in certain conditions, the pathogenesis of this phenomenon remains elusive. Vascular, neural, and hormonal mechanisms have been considered, implicating the role of a wide range of substances, such as prostaglandins, bradykinin, estrogen, platelet-derived growth factor, hepatocyte growth factor, and growth hormone, however, none of these mechanisms provide a unifying explanation (4,5). In digital clubbing, the increased vascularity in the nail-bed leads to hyperplasia of fibrous tissue and edema, resulting in a loss of the hyponychial angle, fluctuance of the nail-bed, and an abnormal phalangeal d

Darier-White disease is a relatively common autosomal dominant genodermatosis caused by mutation in the ATP2A2 gene. It is characterized by multiple warty papules coalescing into plaques in the seborrheic areas and by specific histological skin changes. Palm and sole involvement in Darier-White disease is usually mild, mainly featuring discrete and small keratotic papules. We present a unique case of Darier-White disease presenting with a diffuse, mutilating hystrix-like palmoplantar keratoderma.

Hand hygiene is one of the cornerstones in ensuring effective infection control during the Coronavirus disease 2019 (COVID-19) outbreak. We aimed to investigate the prevalence of new-onset occupational HE during the COVID-19 outbreak in healthcare workers (HCWs) and the clinical course, clinical features, and risk factors of occupational hand eczema (HE). A total of 159 volunteer HCWs (female: n=112; male: n=47, mean age=35.55±7.03 years) working in a pandemic hospital were included. Participants were questioned in terms of daily hand hygiene, use of gloves, and signs and symptoms associated with HE before and during the COVID-19 pandemic. HCWs were divided into two groups classified as non-COVID and COVID, according to the unit they worked in. In our study, 55 participants reported new-onset signs and/or symptoms associated with HE during the COVID-19 pandemic. 59 participants described an increase in signs and/or symptoms associated with HE. The presence of newly-formed or increased signs and/or symptoms associated with HE was found to be 71.7%. A significant increase in dryness, itching, pain/burning, erythema, and scaling was observed (P<0.05). No difference was found between the COVID and non-COVID groups in terms of newly formed and/or increased signs and symptoms (P>0.05). The study included a limited number of participants, and the participants self-reported the signs and symptoms associated with HE. During the COVID-19 period, there has been a significant increase in the signs and symptoms of occupational HE as a result of increased hand hygiene practices in HCWs.

Dear Editor, Nivolumab is a fully human monoclonal antibody that targets the programmed cell death 1 (PD-1) immune checkpoint. It has been approved for its use in several types of advanced solid tumors, including melanoma, lung cancer, and renal cell carcinoma (RCC). The inhibition of PD-1 leads to an enhanced adaptive immune response against tumor cells through the activation of T-cells. Vitiligo-like depigmentation (VLD) is a well-known side-effect in patients with melanoma that are being treated with anti PD-1 therapies (1). However, its development in patients undergoing treatment with nivolumab for cancers other than melanomas has been described very rarely. To our knowledge, herein we report the second case of nivolumab-induced VLD in a patient with metastatic RCC (2). The patient was a 63-year-old man who had a medical history of advanced RCC. He had initially undergone nephrectomy, and three months later he presented with local relapse and lung metastases. He had then received different treatment regimes, presenting with progression each time, until he finally started treatment with nivolumab. Five months after its introduction, the patient developed a disseminated hypochromic eruption. No other drugs were started over that period. He had no personal or family history of vitiligo or other autoimmune disorders. Dermatological examination revealed multiple, symmetrical, well-demarcated, depigmented macules involving his face, neck, torso, hands, and forearms. (Figure 1, a). Preservation of pigment in hair follicles could be seen on the dorsal aspect of his hands (Figure 1, b). Two 4-mm punch biopsies were taken, one from one from a depigmented patch and another from normally pigmented skin. In the first one, immunohistochemical analysis with Melan-A immunostaining demonstrated the absence of melanocytes, whereas melanocytes were present in the second one. A CD-8+ positive infiltrate was present in both biopsies, especially in the first one (Figure 2). The patient was diagnosed with VLD associated with nivolumab therapy. Since the patient was asymptomatic, no treatment was prescribed. He was advised to protect the achromic areas from sun exposure. In our patient, a causal association between the onset of VLD and the treatment with nivolumab cannot be completely ruled out. However, the clinical presentation with flecked macules in sun-exposed areas was consistent with what has been described in other patients presenting with VLD after starting treatment with this chemotherapeutic agent. The time to onset in our case was also within the limits which have been previously reported for this side-effect (16-52 weeks) (3). Therefore, we believe that a causal association is very probable. In patients with advanced melanoma who are treated with PD-1 inhibitors, the development of vitiligo-like lesions has been proved to be associated with improved progression-free and overall survival rates (4,5). This mechanism is not fully understood, but it

The pancreatitis, panniculitis, polyarthritis (PPP) syndrome is a rare skin, joint, and pancreatic disorder, also known as subcutaneous nodular fat necrosis. It results from obstruction of pancreatic ducts with direct secretion of pancreatic enzymes into the bloodstream, causing extra pancreatic fat necrosis with subcutaneous tissue and joint inflammation. It is usually a cutaneous sign of pancreatic cancer or pancreatitis. To our knowledge, this is the first case associated with a pancreatic pseudotumor. We describe a 59-year-old man initially presenting with numerous painful erythematous subcutaneous nodules due to a fibrous pancreatic pseudotumor and its extreme dermatologic disease, resulting in necrosis of the shin and foot so severe that an amputation of the lower leg above the knee was required, a complication not previously described, to our knowledge. We emphasize that PPP syndrome is a cutaneous marker of internal malignancy, most often of pancreatic cancer or pancreatitis, but in this case of a rare pancreatic pseudotumor.