IL-17: a novel player in the pathogenesis of vulvar lichen sclerosus.

Introduction: Vulvar lichen sclerosus (VLS) is a chronic progressive, lymphocyte-mediated inflammatory disease whose pathogenesis is complex and not fully elucidated. Aim: In the current study we have investigated for the first time the expression of interleukin-17 (IL-17) and S100A7 in lesional skin obtained from female individuals with histologically confirmed VLS. Material and methods: In our study we used skin biopsies obtained from female patients with histologically confirmed VLS (n = 20) and skin samples from healthy age- and gender-matched individuals (plastic surgery procedures) (n = 10) serving as controls. The tissue expressions of IL-17 and S100A7 were assessed with an immunohistochemical method. Results: The number of cells showing IL-17 expression was significantly higher in VLS lesional skin as compared to normal skin of healthy controls (p < 0.0001). In VLS lesional skin, IL-17 was expressed in the epidermis and by cells within the inflammatory infiltrate in the upper dermis. The number of cells showing S100A7 expression was significantly higher in VLS lesional skin as compared to normal skin of healthy controls (p < 0.0001). In VLS lesional skin, S100A7 was expressed by suprabasal keratinocytes in epidermis. S100A7 was also expressed by cells within the inflammatory infiltrate in the dermis. Conclusions: The results of our study may suggest the involvement of IL-17 and S100A7 in the pathogenesis of VLS. The better understanding of this disease may lead to the development of novel, effective therapeutic strategies e.g. using well-known biologics IL-17 inhibitors class.

Basal cell carcinoma within rhinophyma: coincidence or relationship?

INTRODUCTION: Rhinophyma is a relatively rare form of rosacea, while basal cell carcinoma (BCC) is the most frequent skin cancer in humans - both diseases prevail in the elderly. AIM: To analyse patients with rhinophyma treated surgically in the Dermatosurgery Unit and look for possible cases with BCC within the rhinophyma. MATERIAL AND METHODS: We performed a retrospective review of all treated rhinophymas in the Dermatosurgery Unit in 2004-2019. RESULTS: Among 140 rhinophyma patients 2 (1.4%) subjects with concomitant clinically diagnosed and histologically confirmed BCC were found, with BCC located in the hypertrophic tissue of the nose. There were no patients with BCC located in other anatomical regions of the skin. Both of these patients were in more advanced age. CONCLUSIONS: Taking into consideration these two conditions: advanced age and anatomical location, typical for BCC, one may speculate that the development of BCC within rhinophyma is rather a simple coincidence. However, more numerous series of patients with rhinophyma are needed to clear the controversy of BCC within rhinophyma hypertrophic tissue.

Immunohistochemical analysis of the expression of selected cell lineage markers (CD4, CD8, CD68, c-Kit, Foxp3, CD56, CD20) in cutaneous variant of lichen planus.

BACKGROUND: Lichen planus (LP) is considered to be an immune-mediated disease of a not fully understood etiology. There are scarce data on the immune cells forming the band-like infiltration in cutaneous LP (CLP). The objective of the current study was to investigate the immunohistochemical pattern of cells forming the infiltrate in CLP by assessing the immunoexpression of selected cell lineage markers. METHODS: The immunohistochemical analysis of the expression of CD4, CD8, CD20, CD56, CD68, c-Kit, and Foxp3 was performed in formalin-fixed paraffin-embedded (FFPE) biopsy specimens from 14 cases of CLP and 11 healthy volunteers. RESULTS: The expression of CD4 (P < 0.001), CD8 (P < 0.001), CD68 (P < 0.001), Foxp3 (P < 0.001), CD56 (v = 0.019), and CD20 (P < 0.001) was significantly higher in lesional skin in CLP compared to healthy controls. The ratio of CD4+ to CD8+ cells in the infiltrate was 1.75:1. The expression of Foxp3, CD56, and CD20 was markedly lower than the expression of CD4 and CD8. There was no statistically significant difference in c-Kit expression between CLP lesions and healthy skin (P = 0.57). CONCLUSIONS: We found a wide variety of immune cells in the inflammatory infiltrate in CLP. The expression of CD4, CD8, CD68, Foxp3, CD56, and CD20 was significantly increased in CLP, while the expression of c-Kit was comparable in lesional skin and controls. The presence of various cell populations, including T regulatory cells, NK cells, and B cells, may indicate a complex pathogenesis of CLP.

Assessment of Effects of Laser Light Combining Three Wavelengths (450, 520 and 640 nm) on Temperature Increase and Depth of Tissue Lesions in an Ex Vivo Study.

BACKGROUND: Lasers are widely used in medicine in soft and hard tissue surgeries and biostimulation. Studies found in literature typically compare the effects of single-wavelength lasers on tissues or cell cultures. In our study, we used a diode laser capable of emitting three components of visible light (640 nm, red; 520 nm, green; 450 nm, blue) and combining them in a single beam. The aim of the study was to assess the effects of laser radiation in the visible spectrum on tissue in vitro, depending on the wavelength and pulse width. METHODS: All irradiations were performed using the same output power (1.5 W). We used various duty cycles: 10, 50, 80 and 100% with 100 Hz frequency. Maximum superficial temperature, rate of temperature increase and lesion depth were investigated. RESULTS: Maximum superficial temperature was observed for 450 + 520 nm irradiation (100% duty cycle). The highest rate of increase of temperature was noted for 450 + 520 nm (100% duty cycle). Maximum lesion depth was observed in case of three-wavelength irradiation (450 + 520 + 640 nm) for 100, 80 and 50% duty cycles. CONCLUSIONS: The synergistic effect of two-wavelength (450 + 520 nm) irradiation was observed in case of maximum temperature measurement. The deepest depth of lesion was noted after three-wavelength irradiation (450 + 520 + 640 nm).

Laugier-Hunziker syndrome: a case report of the pediatric patient and review of the literature.

Laugier-Hunziker syndrome (LHS) is a rare, idiopathic pigmentary disorder especially affecting the lips and oral mucosa. At present, no more than 200 cases of patients diagnosed with LHS syndrome have been described worldwide. To date, three patients under the age of 20 have been described, including the youngest patient who is a 12-year-old child. The exact etiology of LHS still remains uncertain, as there is no evidence of systemic symptoms or increased cancer risk. The final diagnosis of LHS is possible after the exclusion of other, more serious diseases involving skin-mucosal hyperpigmentation, mainly Peutz-Jeghers syndrome (PJS) and Addison's disease (AD). Herein, we present a 16-year-old patient who has been diagnosed with oral hyperpigmentation since the age of 13. We reviewed the clinical and histological findings. In addition, we discussed the differential diagnosis of mucocutaneous hyperpigmentation.

Photodynamic diagnosis and photodynamic therapy in basal cell carcinoma using a novel laser light source.

The aim of the present study was evaluating the effects and safety of new laser light source in PDD and PDT of basal cell carcinoma, BCC. The patients presented challenging localizations of the tumor or tumor combined with Gorlin syndrome. The PDD and PDT was performed in 50 patients with 54 histologically confirmed BCCs. The photosensitizer precursor, 5-ALA in cream, was used and the tumors were then illuminated, for PDD at 405 nm, and for PDT at 638 nm by means of newly designed laser. The novel feature of the laser was the combination of violet and red light in a single fiber output which enabled us to perform PDD and PDT alternatingly. The patients received one or more PDT sessions and they were observed during the next 36 months. The complete responses (CR, remissions) of the lesions were considered as no visible tumor after that time period. CR were observed in 87 % of the lesions in the entire group of patients. The results of present study show that the new laser allowing for both PDD and PDT was effective in producing satisfactory responses in the treatment of basal cell carcinoma.

Paradoxical Skin Reaction to Certolizumab, an Overlap of Pyoderma Gangrenosum and Psoriasis in a Young Woman Treated for Ankylosing Spondylitis: Case Report with Literature Review.

INTRODUCTION: Biologic agents form an indispensable part of modern therapeutic regimens for the treatment of severe inflammatory diseases, especially in the fields of rheumatology, dermatology and gastroenterology. They are favoured by both physicians and patients due to their high effectiveness, good patient tolerance and safety. However, interference in the regulation and dynamics of inflammatory cytokines can on occasion lead to an onset of a dermatological condition also known as paradoxical skin reaction. Here, we present a case of paradoxical skin reaction induced by certolizumab. CASE REPORT: A young woman with ankylosing spondylitis developed a severe and complex cutaneous reaction after 6 months of otherwise successful treatment with certolizumab. The diagnosis of a rare paradoxical cutaneous reaction post anti-tumour necrosis factor alpha treatment was based on overlapping features of pyoderma gangrenosum and palmoplantar pustular psoriasis. Alopecia developed and there was also nail involvement. Treatment proved to be challenging as the disease did not remit after the patient ceased treatment with certolizumab. The patient was started on a combination of secukinumab and methotrexate to control the symptoms, with a promising outcome. CONCLUSION: Paradoxical skin reactions are an emerging clinical entity that require further research in order to establish risk factors and best personalized treatment.

Xanthoma-like Skin Changes in an Elderly Woman with a Normal Lipid Profile.

Dear Editor, An 83-year-old woman developed yellow-brownish infiltrates, nodules, and tumors mimicking xanthomas, mostly involving the periorbital and chest area within three months (Figure 1). She had no abnormalities in serum cholesterol or triglycerides levels. A detailed laboratory analysis revealed the presence of mild monoclonal gammopathy with a presence of immunoglobulin G (IgG) kappa light chains; however, according to hematologist consultation, it did not require medical intervention. Imaging assessment and ultrasound examination did not show any specific involvement of internal organs. The skin biopsy demonstrated necrobiotic areas alternated with foci of xanthogranulomatous infiltration throughout the reticular dermis with extension into subcutaneous tissue. The granulomatous infiltrate was composed of epithelioid, foamy histiocytes in addition to conspicuous giant cells of the Touton type and foreign body type, as well as variable numbers of lymphocytes, plasma cells, and neutrophiles. Lipid vacuoles were seen within the foci of necrobiosis and xanthogranulomatous infiltration (Figure 2). Two months after first admission to our department, the first signs of necrosis within the lesions were noted, and massive necrosis of skin lesions occurred after the following 5 months (Figure 1). Based on the clinical manifestation and histological and laboratory findings, the diagnosis of necrobiotic xanthogranuloma (NXG) was established. In our patient, the extremely late onset of the disease, its very aggressive course, and the absence of malignant hematological disorder were remarkable. The general condition improved after local treatment and a low dose of prednisone. However, patient anamnesis revealed myocardial infarction in the past, congestive heart failure, and atrial fibrillation. Eventually, the patient died due to acute heart failure before alkylating agents could be administered; we consider the patient's death to have been unrelated to NXG. NXG is a rare, chronic granulomatous disorder which was first described in 1980 by Kossard and Winkelmann (1). Currently, less than one hundred fifty cases of this syndrome have been reported in the literature worldwide (2,3). The disease occurs during adulthood, slightly more frequently in women, and usually after the age of 60 years, although the youngest reported patient was 17 years old (3). The disease initially manifests as xanthoma-like eruptions of yellowish or red-orange papules and nodules that coalesce into indurated plaques (4). The size of the lesions typically increases over time or with the next recurrences. In comparison to hyperlipemic and normolipemic xanthomas, the lesions are firmer, more prominent, and more polymorphic (3) with superficial telangiectasias, sometimes erythematous and/or violaceous borders, and atrophy (5). Ulcerations of the lesions were observed in about 50% of patients and tended to be extensive and progressive (4). Skin lesions of NXG can occur anywhere on the body. However, about two-thirds of patients had periorbital involvement, particularly on the upper and/or lower eyelids or elsewhere on the face. The second most commonly affected site was the trunk, predominantly the chest (3-6). However, many skin lesions first appear on the trunk or extremities and subsequently involve the periorbital area (4). More than one body area was affected in about 90% of the published cases (3,4). In individual cases, the occurrence of NXG was noted within scars, after trauma, or in a previously X-ray irradiated area (5). Lesions may be asymptomatic; however, over half of patients asked reported various symptoms, predominantly itching but also burning, tenderness, and even pain (4,5). Periorbital skin lesions are often accompanied by ophthalmic manifestations, mainly scleritis, choroiditis, or conjunctivitis (3), and with complications such as blepharoptosis, restricted ocular motility, and proptosis (4,5). Extracutaneous lesions are most commonly seen in the respiratory tract, including the lungs and larynx, followed by the myocardium, oral cavity, skeletal muscles, kidneys, ovaries, intestine, and other sites (5,6). Extracutaneous involvement was reported in less than 20% of cases (3), but its frequency seems to have increased in recent years (5). Regarding laboratory abnormalities, the majority of patients with NXG (70% and up to 90% depending on the studied population) have a monoclonal gammopathy (more often IgG-kappa than IgG-lambda). Elevated erythrocyte sedimentation rate, anemia, leukopenia, low C1 and C4 levels, and cryoglobulinemia are also frequently present (3-6). Incisional biopsy is recommended to confirm the diagnosis of NXG, but correlations between the clinical presentation and specific histopathologic findings have been poorly characterized so far. The histopathology shows an inflammatory infiltrate composed of macrophages, foam cells, plasma cells, and other inflammatory cells as well as Touton and foreign body-type giant cells in the dermis and subcutaneous tissue. Necrobiosis is usually present, and nodular lymphoid aggregates are common. Cholesterol clefts or asteroid bodies are rare or absent. The epidermis may be atrophic or normal. Special stains are not helpful in establishing the diagnosis of NXG, but immunohistochemistry for CD68 is positive while it is always for CD1a and PS100 negative, like in non-X histiocytosis (4,5). In patients without a known myeloproliferative disorder, bone marrow biopsy may reveal atypical or increased plasma cells and, very rarely, true multiple myeloma (5). As mentioned above, NXG can be a manifestation of multiple myeloma. However, chronic lymphocyte leukemia, B-cell lymphoma, and other lymphoproliferative diseases have also been reported in patients with NXG (3). Remarkably, hematological disorders may emerge many years before or after the onset of skin lesions (even up to 11 years) (4). According to available literature data, the course of the disease is usually chronic and slowly progressive, and the prognosis is relatively good in the absence of co-occurrence of malignant hematological disorders ([5-7). Aside from hyperlipemic and normolipemic xanthomas, the differential diagnosis of NXG includes multifocal necrobiosis lipoidica, granuloma annulare, foreign-body granuloma, juvenile xanthogranuloma, rheumatoid nodules, and amyloidosis (4). In 5 cases from the literature, xanthoma and NXG were present at the same time (3). Despite several hypotheses, the etiopathogenesis of NXG remains unknown (3,4,8). For that reason and due to the rarity of the disease, the optimal therapy has not been not defined. Frequently, chlorambucil or melphalan have been used alone or in combination with prednisone (4). Treatment may result in remission of symptoms on the skin, but it does not provide a permanent cure (8). There are also single reports of the successful use of thalidomide, lenalidomide, cyclophosphamide, dexamethasone, interferon 2a and 2b, plasmapheresis and hydroxychloroquine, azathioprine, infliximab, and autologous bone marrow transplantation (3). Methotrexate seems to be ineffective (9). Local therapy, including local steroids, laser CO2, or radiotherapy, results in partial improvement (3,4). Skin lesions which relapsed or were unresponsive to treatment could be excised surgically and the defects resurfaced with skin grafts. [2].

Diffuse melanosis cutis related to dermal micrometastases as the first clinical symptom of distant metastatic malignant melanoma: Case report.

RATIONALE: Diffuse melanosis cutis (DMC) is a very rare sign of malignant melanoma progression. The condition usually develops after approximately one year from melanoma diagnosis in a patient with metastatic tumors and after anticancer treatment with cytostatic medications. PATIENT CONCERNS: A 72-year old Caucasian man was admitted to the Department of Dermatology with DMC for 4 months and the history of two melanomas treated surgically 30 years and 9 months before present hospitalization. DIAGNOSIS: Histological and immunohistochemical examinations of DMC biopsy indicated melanoma metastatic cells as well as free deposits of melanin and melanophage presence in the dermis. INTERVENTIONS: The patient refused to the treatment. OUTCOMES: The patient died eight months after DMC appeared. LESSONS: DMC is a rare presentation of advanced MM and is a bad prognostic factor. The pathomechanisms of the discoloration of the skin are not fully explained. The role of micrometastases, as well as melanin precursors, released during lysis of MM metastases, and growth factors may play a role in the development of the symptom.