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.

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.

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 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.

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.