Cutaneous Toll-like Receptor 9 Pre-Defines Hydroxychloroquine Dosage in Patients with Both Discoid and Subacute Lupus Erythematosus.

Background and Objectives: Cutaneous lupus erythematosus (CLE) presents clinically heterogeneous manifestations, partially explained by the different expression of Toll-like receptors (TLRs) type 8 and 9, located to endosomal compartments where they are poised to recognize microbial nucleic acids. This disease is empirically treated with hydroxychloroquine (HCQ), which is hallmarked with a safe and effective profile, but induces a slow and sometimes clinically insufficient therapeutic response. Currently, no biomarkers predictive of response are validated or even proposed in the scientific literature. We aimed to evaluate endosomal TLR type 7, 8 and 9 as predictive biomarkers of HCQ efficacy. Materials and Methods: We conducted a case-control study comparing CLE patients retrospectively assigned to three subgroups based on 3-6-month Cutaneous LE Disease Area and Severity Index (CLASI) reduction upon treatment with HCQ (I = <40% vs. II = 40-80% vs. III = >80%). Before HCQ, lesional skin specimens were collected in untreated CLE and through immunohistochemistry; TLR-7, -8 and -9 expression was evaluated in the epidermis and the lymphocytic infiltrate was evaluated in the dermis. Results: Sixty-six lesional skin biopsies were compared with healthy controls. CLE patients displayed lower epidermal expression of total TLR 8 and 9 as well as infiltrating TLR-8, TLR9 + lymphocytes compared to controls. High HCQ responders differed from low responders for TLR-9 positivity (high vs. low) and for the lymphocytic dermal infiltrate (high vs. low). Conclusions: TLR9 could be envisaged as a possible biomarker to predict HCQ response level and dosage in CLE patients.

Scalp vascularization as a marker of topical minoxidil treatment efficacy in patients with androgenetic alopecia.

Introduction: Androgenetic alopecia is the most common type of non-cicatricial hair loss both in male and female patients. The pathomechanism of the disease involves chronic and progressive miniaturization of hair follicles, which leads to the conversion of terminal hair to vellus hair. Minoxidil is a first-line drug in the treatment of female pattern hair loss (FPHL). Aim: The study is aimed at verifying whether the degree of scalp vascularization has an impact on the efficacy of topical 5% minoxidil treatment. Material and methods: The study involved a group of 76 patients diagnosed with FPHL, who underwent a scalp biopsy for a histological examination of their scalp vascularization. The patients were divided into two groups, with rich and poor scalp vasculature. In all patients, topical treatment with 5% minoxidil was applied for a minimum of 6 months, followed by video-trichoscopic assessment. Results: A significant increase in the total count was observed 6 months into the treatment as compared with baseline, and a decrease in the number of single hair per follicle. It was observed that the number of single hair units had gone down in 50.67% of patients. The study also demonstrated an increase in the total hair count in 57.33% of patients as well as no drops in the total count in 68% of patients, following 6 months of treatment. Conclusions: Patients responded equally well to the applied topical minoxidil treatment, irrespectively of the number of blood vessels in the scalp.

Dendritic cells may help differentiate discoid lupus erythematosus alopecia from lichen planopilaris.

Introduction: Primary cicatricial alopecia (PCA) encompasses a heterogeneous group of inflammatory diseases characterized by the replacement of hair follicle structures by fibrous tissue. Discoid lupus erythematosus (DLE) and lichen planopilaris (LPP) are the most common causes of scarring alopecia. The distinction between both entities is often challenging because of significant clinical and histopathological overlap. Aim: We hypothesized that dendritic cells which are implicated in PCA pathogenesis can provide a reliable histopathological clue to distinguish between these two entities. Material and methods: In a retrospective cohort study including 51 patients diagnosed with LPP and DLE we mapped and quantified the distribution of dendritic cells. Cell count in lesional skin was performed on immunohistochemistry by using characteristic monoclonal antibodies to specific subpopulations of dendritic cells. Results: We demonstrated that almost all subpopulations of dendritic cells were highly expressed in lesional skin of discoid lupus erythematosus patients in comparison with lichen planopilaris ones. Conclusions: In the light of this observation, dendritic cells might be used as an additional clue in differential diagnosis of PCA.

Dermoscopic features causing confusion between melanoma and benign nevi in clinical diagnosis - case series.

The vast majority of melanoma lesions show typical dermoscopic features such as the presence of atypical pigmented network, the variety of colors within nevi, the asymmetry of structures and the presence of structureless areas. The clinical appearance of melanocytic lesions evolving over time also constitutes a clue to discover their malignant potential. Albeit there are some cases that do not exhibit typical dermoscopic and clinical findings suggesting their malignant potential. A CASE REPORT: We report 4 cases of melanoma with their equivocal dermoscopic images and ambiguous clinical pictures. We acknowledge dermoscopic features such as: the presence of variform, peripheral globules suggesting the possible growth of the nevus, the presence of terminal hair within the melanoma lesion and we confirm that only on the basis of this criterion we cannot qualify such melanocytic lesions to the benign category. We also report the case of the two-component lesion consisted of reticular-homogenous pattern and concentrated globules in the superior pole of the nevus with no significant signs of evolution during one year period of surveillance and the case of the two-component lesion consisted of reticular - homogenous pattern with focal areas of higher density network and the presence of polymorphous, dotted, coiled, comma-like vessels which met the criterion of the ugly duckling sign. Dermoscopy is the most useful noninvasive diagnostic tool designed to discriminate skin nevi. Despite its benefits, the interpretation of a dermoscopic image is not always unequivocal. Some melanoma lesions exhibit only single features included in the assessment algorithms used in everyday dermatological practice such as: the ABCDE rule, the pattern analysis, the 7-points Glasgow checklist, the Menzies method, the 3-point checklist. The presence and the shape of vessels within nevi also constitute an important diagnostic indicator of melanoma. Dotted vessels are related to early stages of melanoma and polymorphous, elongated, linear, vessels are connected with more advanced stages. Therefore, dermoscopic examination should be performed by trained physicians. In case when predicted biological potential of melanocytic lesions is uncertain the excision of suspected lesions followed by histopathological examination should be carried out.

The role of family history and its influence on the onset time in female pattern hair loss.

INTRODUCTION: Female pattern hair loss (FPHL) is one of the most common causes of hair loss in women. Genetics plays an important role in the development of the disease, but the etiopathogenesis and the inheritance pattern in women remain unexplained. AIM: To determine the extent to which FPHL is of genetic origin in women from the Polish population and whether a positive family history is a risk factor for its earlier onset. MATERIAL AND METHODS: Family histories of 111 unrelated female patients with FPHL and 129 female patients without hair thinning were analysed. FPHL was diagnosed based on a detailed medical history, the clinical picture and trichoscopic features. RESULTS: A positive family history was noted in 69 (62.2%) patients with FPHL. In 32 (28.8%) patients from that group, more than one person in the family suffered from hair loss, whereas in the healthy group, the same was true of only 4 patients (3.1%) (p < 0.0001). A positive family history on the mother's side proved statistically significant for FPHL patients. In the case of 20 (18%), hair loss had been identified in their grandparents, while the healthy group had a negative history in that respect. A positive family history of hair loss in grandparents was three times more frequent in the group of patients with the disease onset before 40. CONCLUSIONS: A positive history on the mother's side may be of great significance for FPHL development. Hair loss in more than one family member and in one's grandparents may also indicate a higher risk of disease development.

Leukaemia cutis for clinicians, a literature review.

Leukaemia cutis (LC) describes infiltration of the skin by leukaemia cells, resulting in clinically identifiable cutaneous lesions. LC has a wide range of clinical manifestations, which can make it difficult to distinguish LC from other skin changes. In a group of patients, LC can be the first manifestation of leukaemia, therefore skin biopsy is crucial for the diagnosis. In this mini review, we discuss various types of leukaemia most frequently represented in leukaemia cutis, in both children and adults and skin changes in multiple myeloma, focusing on the clinical presentation of LC and prognosis in patients.

Dendritic cells as predictive markers of responsiveness to hydroxychloroquine treatment in primary cicatricial alopecia patients.

Primary cicatricial alopecia (PCA) encompasses a diverse group of inflammatory diseases characterized by the irreversible replacement of hair follicle structures by fibrous tissue. Although the pathogenesis of PCA remains not fully understood, the key to its understanding might be the location of dendritic cells (DCs) inflammatory infiltrate. One of the systemic therapy of choice in PCA patients is hydroxychloroquine (HCQ). We hypothesized that DCs are implicated in PCA pathogenesis and that they might constitute the biological target of HCQ treatment. For these reasons, we investigated whether DCs could affect the antimalarial responsiveness, and if DCs might be used as predictive factor of responsiveness to HCQ. In this retrospective cohort study, 65 patients diagnosed with PCA were grouped accordingly to their response to HCQ therapy. Skin biopsies had been taken before the treatment was started. Cell count was performed on immunohistochemistry by using characteristic monoclonal antibodies to specific subpopulations of DCs. In almost every second patient (47.7%), we observed remission of the disease during HCQ treatment. The number of plasmacytoid and myeloid DCs as well as Langerhans cells in lesional skin of HCQ responders was higher in comparison with HCQ nonresponders. Moreover, in a predictive model receiver operating characteristic (ROC curve) we showed that plasmacytoid DCs might be used as a predictive factor of responsiveness to HCQ. The results of this study are important as identifying biomarkers for responsiveness to a HCQ therapy will be helpful to individualize treatment and make it more effective.

The level of stress and the assessment of selected clinical parameters in patients with androgenetic alopecia.

Androgenetic alopecia is the most common type of hair loss both in male as well as female patients. It is a type of non-cicatricial hair loss. Pathophysiology of the disease remains largely unknown. It is believed that the occurrence of FPHL (female pattern hair loss) is linked with cellular insensitivity to androgens. Human hair does not only represent beauty, health and youth, but it also has a significant impact on one's self-esteem. For many patients, hair loss is a stigmatizing experience, many of them complain about a lower quality of life, anxiety or even depression. AIM: Aim of the study was to evaluate the levels of selected clinical parameters, including exposure to stress and disease progression based on the Ludwig scale, and of the applied therapies in a group of female patients with androgenetic alopecia. MATERIALS AND METHODS: A group of 106 patients with androgenetic alopecia was analyzed with respect to their age, duration of disease, disease progression based on the Ludwig scale, family history of AGA, exposure to stress (with the level of stress subjectively assessed by the patients using a score of 1 to 10), and treatment modality. Comparison of the results will be carried out with the help of the Statistica software, using the Student's t-test or its non-parametric equivalent. RESULTS: Patients reported very high levels of stress exposure: 7 and 8 on a scale of 1 to 10. The type of treatment applied (local vs. systemic) was of no significance with respect to the alleviation of stress. Disease progression was not found to correlate with the level of stress. When analyzing disease progression, using the Ludwig classification scale, most of the patients met the criteria of type I-2 (24.74%). As regards the comparison of treatment modalities in the study group, a great majority of patients was treated with topical agents in the form of scalp massage liquids (80.00%), while 17.14% of the study population underwent systemic treatment. A small percentage of patients also resorted to esthetic medicine procedures (3.81%), and 22.86% of them used dietary supplements or OTC topical agents. CONCLUSIONS: High levels of stress exposure reported by patients most probably stemmed from the symptoms of the disease itself, as the study population was quite diverse in terms of their levels of professional activity and the type of profession performed.

Is hormone testing worthwhile in patients with female pattern hair loss?

Androgenetic alopecia (AGA) is the most common type of hair loss both in male and female patients. As regards its etiopathology, it is postulated that hair follicles grow sensitive to androgens in persons who are genetically predisposed to it. In the pathomechanism of the disease, hair follicles undergo miniaturization. AIM: The aim of the study was to evaluate the levels of selected hormones (sex hormones, adrenal and thyroid hormones), and the results of laboratory tests (iron metabolism) performed in a group of female patients with AGA in order to specify which of those tests should be taken during the diagnostic process in such patients. MATERIALS AND METHODS: Test results and types of therapies have been analyzed for a group of 106 adult female patients (of different age) with female pattern hair loss (FPHL) of different duration. Selected hormone parameters have been analyzed as well as iron metabolism, BMI ( body mass index), and signs of androgenization in the patients' histories (presence of menstrual disorders, hirsutism and acne). Additionally, their insulin levels were measured. RESULTS: The most common hormonal disorders in the study population involved increased concentrations of sex hormone binding globulin (SHBG) in 38.8%, decreased concentration of total testosterone in 25.4%, increased antibody titers against thyroid peroxidase (ATPO) in 17.3%, decreased concentrations of dihydroepiandrostendione (DHEAS) in 15.6%, and increased concentrations of insulin in 12.6%. Increased concentrations of free testosterone were only observed in 6.8 % of the study participants, and increased concentrations of cortisol were revealed in 6.7% of them. 40% of the patients complained about symptoms related to menstrual disorders, hirsutism and acne. Sex hormone concentrations did not correlate with the reported symptoms, and test results in that sub-group were not found to significantly differ from the rest of the patients who did not report signs of hyperandrogenism. CONCLUSIONS: In spite of the fact that nearly half of the patients reported symptoms which may be suggestive of hormonal disorders, no significant abnormalities were revealed in hormone tests.

The impact of therapeutic modalities on patients with atopic dermatitis, psoriasis and vitiligo treated with phototherapy in the Jagiellonian University Outpatient Clinic.

Phototherapy involves repeated exposure of the skin to ultraviolet light and is commonly used in various dermatological diseases such as: psoriasis, atopic dermatitis and vitiligo. It constitutes a highly preferable treatment modality due to acceptable benefit/risk ratio. AIM: The aim of the study is to characterize parameters such as: number of PUVA or NB-UVB sessions, cumulative doses of phototherapy, values of minimal erythema doses (MED), periods of the year during phototherapy sessions in patients with vitiligo, atopic dermatitis and psoriasis attending the Jagiellonian University Outpatient Clinic. MATERIALS AND METHODS: This was a retrospective study of 50 Caucasian patients who attended the Department of Dermatology of the Jagiellonian University Outpatient Clinic over a period of one and a half years (from November 2016 to May 2018). RESULTS: We report that PUVA-therapy is more effective in achieving complete remission (CR) of skin lesions in patients with atopic dermatitis and vitiligo, compared to NB-UVB irradiations. In all patients enrolled to the study, apart from psoriatic patients treated with NB-UVB, the cumulative doses of UVA+P/NB-UVB were significantly higher during autumn/winter time than spring/summer time. Patients with vitiligo required higher cumulative doses and they needed more phototherapy sessions regardless the method of phototherapy in order to achieve CR, compared to other patients. The patients with psoriasis required, statistically significant, faster NB-UVB dose enhancement in order to maintain the efficacy of treatment than those with other diseases. CONCLUSIONS: Phototherapy constitutes an efficient, safe and accessible (in Poland and many other countries) method of therapy but there is still much to be discovered about the factors that affect its efficacy. Finding out more data relating to this issue could enable more effective treatment planning for particular patients and it would have an important economic impact.

Influence of long-term steroid use on lymphocytes subsets in patients with lupus erythematosus.

Glucocorticosteroids (GCS) were used for decades to modulate immune system. Numerous studies were performed to evaluate their effects on cell mediated response and humoral immunity. AIM: The aim of study was to evaluate the potential associations between chronic use of GCS and immunological tests. PATIENTS AND METHODS: A cohort of patients (n=15) from Department of Dermatology of University Hospital of Cracow, Poland with cutaneous lupus erythematous were identified on individual record review. Flow cytometry was performed to determine the counts of circulating subsets of lymphocytes. Additionally, using nephelometry, serum concentrations of immunoglobulins (i.e. IgA, IgM, IgG) were assessed. RESULTS: A cohort of patients (n=15) from Department of Dermatology of University Hospital of Cracow, Poland with cutaneous lupus erythematous were identified on individual record review. Flow cytometry was performed to determine the counts of circulating subsets of lymphocytes. Additionally, using nephelometry, serum concentrations of immunoglobulins (i.e. IgA, IgM, IgG) were assessed. CONCLUSIONS: A cohort of patients (n=15) from Department of Dermatology of University Hospital of Cracow, Poland with cutaneous lupus erythematous were identified on individual record review. Flow cytometry was performed to determine the counts of circulating subsets of lymphocytes. Additionally, using nephelometry, serum concentrations of immunoglobulins (i.e. IgA, IgM, IgG) were assessed.

Autoimmunity in lichen planopilaris patients.

Lichen planopilaris (LPP) is a rare, scarring form of alopecia with lymphocytic pattern. Due to the destruction of epithelial hair follicle stem cells in the bulge, it represents an irreversible condition. Antinuclear antibodies have been used for decades as diagnostic biomarkers of several rheumatological diseases. AIM: The aim of study was to determine the frequency of anti-nuclear antibodies positivity and subsequently analyze the presence of specific antibodies in LPP patients. MATERIALS AND METHODS: 57 patients (aged 28-79, female 96%) were included in the study. Patients with LPP were treated in Department of Dermatology of University Hospital in Cracow, Poland and were identified on individual record review. Antinuclear antibodies were detected using indirect immunofluorescence on HEp-2 cells and immunoblot test. RESULTS: Antinuclear antibodies were detected in sera of 48 out of 57 LPP patients (84,2%). In 22 (46%) patients antinuclear antibodies specificity could be defined, anti-dsDNA and anti-Ro/anti-SSA being most common. CONCLUSIONS: Antinuclear antibodies were detected in sera of 48 out of 57 LPP patients (84,2%). In 22 (46%) patients antinuclear antibodies specificity could be defined, anti-dsDNA and anti-Ro/anti-SSA being most common.

How to Optimize Trichoscopy for Evaluation of Scalp Vessels.

INTRODUCTION: Trichoscopy greatly facilitates clinical diagnosis in patients with hair loss and may decrease the necessity for histopathological examination. Structures which may be revealed by trichoscopy include hair shafts, hair follicle openings, the perifollicular epidermis, and cutaneous microvessels. Cutaneous microvessels revealed in trichoscopy may vary in type and number depending on the scalp area, type of the disease, and its activity. Firm direct pressure (diascopy) might result in their blanching, but as of yet, there are no studies on the types of vessels that do or do not blanch on applying pressure. METHODS: We studied interfollicular twisted loops in 16 cases of biopsy-confirmed scalp psoriasis and 37 cases of arborizing vessels in normal subjects and seborrheic dermatitis patients. RESULTS: We observed that all arborizing red line vessels blanched on applying pressure. Instead, the vast majority of twisted and simple loops, despite their vascular nature, did not blanch on performing diascopy. CONCLUSION: In the light of these findings, diascopy of vascular changes in hair loss patients might provide additional clues for a proper diagnosis, especially in differentiating scalp psoriasis, seborrheic dermatitis, and discoid lupus erythematosus.

The Skin as a Mirror of Internal Disease: Comorbidities and Epidemiology of Acne Vulgaris and Adult Female Acne - A Cross-sectional Study and Current State of Knowledge.

Acne vulgaris is a common skin condition affecting an increasing number of adults and might be a clue to identifying systemic disease. Objective of this study is assessment of the demographic and clinical characteristic, including comorbidities, of patients with acne with a special focus on adult female acne (AFA). This cross-sectional study analyzed the medical records of 354 patients with acne (323 outpatients and 31 hospitalized). Data concerning patient age, sex, lesions morphology and distribution on body areas, duration of the disease, Body Mass Index, and dermatologic and systemic comorbidities were collected. 61% of all patients were female, 45.37% of women were classified as AFA. The median age of patients with acne was 24 years and 32.5 years for AFA. The face was the most commonly affected area; patients with AFA had lesions on their back than less frequently non-AFA. Predominant eruptions were pustules and papules. 38.7% of patients had concomitant systemic chronic disease, 15.25% had an endocrinologic disorder, and 6.21% had thyroid gland dysfunction. Women with AFA had endocrinologic disorders more frequently (P=0.002), whereas cutaneous signs of hyperandrogenism were observed less frequently than in the non-AFA group (P=0.034). AFA possess distinct clinical features and it should raise suspicion towards possible underlying endocrinologic disturbance.