Malignancy in systemic lupus erythematosus: relation to disease characteristics in 92 patients - a single center retrospective study.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a variable clinical manifestation, potentially leading to death. Importantly, patients with SLE have an increased risk of neoplastic disorders. Thus, this study aimed to comprehensively evaluate the clinical and laboratory characteristics of patients with SLE and with or without malignancy. METHODS: We conducted a retrospective analysis of medical records of 932 adult Caucasian patients with SLE treated at the University Hospital in Kraków, Poland, from 2012 to 2022. We collected demographic, clinical, and laboratory characteristics, but also treatment modalities with disease outcomes. RESULTS: Among 932 patients with SLE, malignancy was documented in 92 (9.87%), with 7 (7.61%) patients experiencing more than one such complication. Non-hematologic malignancies were more prevalent (n = 77, 83.7%) than hematologic malignancies (n = 15, 16.3%). Patients with SLE and malignancy had a higher mean age of SLE onset and a longer mean disease duration than patients without malignancy (p < 0.001 and p = 0.027, respectively). The former group also presented more frequently with weight loss (odds ratio [OR] = 2.62, 95% confidence interval [CI] 1.61-4.23, p < 0.001), fatigue/weakness (OR = 2.10, 95% CI 1.22-3.77, p = 0.005), and fever (OR = 1.68, 95% CI 1.06-2.69, p = 0.024). In the malignancy-associated group, we noticed a higher prevalence of some clinical manifestations, such as pulmonary hypertension (OR = 3.47, 95% CI 1.30-8.42, p = 0.007), lung involvement (OR = 2.64, 95% CI 1.35-4.92, p = 0.003) with pleural effusion (OR = 2.39, 95% CI 1.43-3.94, p < 0.001), and anemia (OR = 2.24, 95% CI 1.29-4.38, p = 0.006). Moreover, the patients with SLE and malignancy more frequently had internal comorbidities, including peripheral arterial obliterans disease (OR = 3.89, 95% CI 1.86-7.75, p < 0.001), myocardial infarction (OR = 3.08, 95% CI 1.41-6.30, p = 0.003), heart failure (OR = 2.94, 95% CI 1.30-6.17, p = 0.005), diabetes mellitus (OR = 2.15, 95% CI 1.14-3.91, p = 0.011), hypothyroidism (OR = 2.08, 95% CI 1.29-3.34, p = 0.002), arterial hypertension (OR = 1.97, 95% CI 1.23-3.23, p = 0.003), and hypercholesterolemia (OR = 1.87, 95% CI 1.18-3.00, p = 0.006). Patients with SLE and malignancy were treated more often with aggressive immunosuppressive therapies, including cyclophosphamide (OR = 2.07, 95% CI 1.30-3.28, p = 0.002), however median cumulative cyclophosphamide dose in malignancy-associated SLE subgroup was 0 g (0-2 g). Interestingly, over a median follow-up period of 14 years (ranges: 8-22 years) a total of 47 patients with SLE died, with 16 cases (5.28%) in the malignancy-associated SLE group and 31 cases (5.73%) in the non-malignancy SLE group (p = 0.76). The most common causes of death were infections (21.28%) and SLE exacerbation (8.51%). CONCLUSION: The study highlights the relatively frequent presence of malignancies in patients with SLE, a phenomenon that demands oncological vigilance, especially in patients with a severe clinical course and comorbidities, to improve long-term outcomes in these patients.

Clinical and laboratory characteristics of early-onset and delayed-onset lupus nephritis patients: A single-center retrospective study.

BACKGROUND: Lupus nephritis (LN) manifests systemic lupus erythematosus (SLE) and is characterized by various clinical and laboratory features. This study aimed to comprehensively evaluate the characteristics of LN patients according to the time of LN diagnosis: early-onset (LN diagnosed within one year from SLE diagnosis) vs. delayed-onset (LN diagnosed more than one year after SLE diagnosis). METHODS: We conducted a retrospective analysis of medical records from all SLE patients treated at the University Hospital in Kraków, Poland, from 2012 to 2022. We collected data on demographic, clinical, and laboratory characteristics, including histological findings, treatment modalities, and disease outcomes. Statistical analyses were performed to identify factors impacting LN development and prognosis. RESULTS: Among 331 LN patients, early-onset was diagnosed in 207 (62.54%) and delayed-onset was documented in 122 cases (36.86%). In 2 (0.6%) LN cases, the time of first kidney manifestation in the SLE course was unknown. Delayed-onset LN had a higher female-to-male ratio and younger age at SLE diagnosis. This group was associated with more severe clinical manifestations. In turn, studied subgroups did not differ in internist comorbidities, kidney histopathology, and family history regarding autoimmune diseases. Delayed-onset LN exhibited a higher frequency of anti-dsDNA, anti-Smith, anti-Ro, anti-RNP, and anti-cardiolipin IgG autoantibodies. During a 14-year follow-up period, 16 patients died. Mortality rate and causes of death were comparable in both analyzed subgroups. CONCLUSIONS: More severe clinical manifestations in delayed-onset LN prompt strict monitoring of non-LN SLE patients to diagnose and treat kidney involvement early. Also, recognizing the higher frequency of autoantibodies such as anti-dsDNA or anti-Smith in delayed-onset LN underscores the potential value of autoantibody profiling as a diagnostic and prognostic tool.

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.

Molecular Proof of a Clinical Concept: Expression of Estrogen Alpha-, Beta-Receptors and G Protein-Coupled Estrogen Receptor 1 (GPER) in Histologically Assessed Common Nevi, Dysplastic Nevi and Melanomas.

Background and Objectives: Epidemiologic data show significant differences in melanoma incidence and outcomes between sexes. The role of hormonal receptors in the pathogenesis of melanocytic lesions remains unclear, thus we performed this study aiming to assess estrogen receptors expression in different melanocytic lesions. Materials and Methods: We performed a cross-sectional study that included 73 consecutively excised melanocytic lesions. Estrogen receptor alpha (ERα), beta (ERß), and G-protein coupled estrogen receptor (GPER) expression was analyzed in melanocytes and keratinocytes of common nevi, dysplastic nevi, melanoma, healthy skin margin, and in sebaceous and sweat gland cells. Results: ERß expression was higher in dysplastic nevi margin melanocytes compared to common nevi (p = 0.046) and in dysplastic nevi keratinocytes compared to melanoma keratinocytes (p = 0.021). ERß expression was significantly higher in margin melanocytes compared to melanoma melanocytes (p = 0.009). No difference in ERß expression was shown between melanocytes of three types of lesions. GPER expression was higher in nuclei and cytoplasm of dysplastic nevi (p = 0.02 and p = 0.036 respectively) and at the margin compared to melanoma. GPER expression was lower in sebaceous glands of tissue surrounding common nevi (p = 0.025) compared to dysplastic nevi. GPER expression was higher in skin margin tissue melanocytes (p = 0.016 nuclear, p = 0.029 cytoplasmic) compared to melanoma melanocytes. There were no differences in ERα expression between the melanocytic lesions. Conclusion: Further large-scale studies are warranted to investigate the potential role of ERß and GPER in the pathogenesis of melanocytic lesions.

Mask-induced Koebner phenomenon and its clinical phenotypes: A multicenter, real-life study focusing on 873 dermatological consultations during COVID-19 pandemics.

During COVID-19 pandemic, wearing masks for prevention became mandatory but evidence suggest that is also detrimental for skin. Although facial dermatoses due to masks increase in both healthcare workers and general population, a pathogenetic hypothesis remains still elusive. We aimed to evaluate the prevalence of dermatological consultations due to Koebner triggered dermatoses In this prospective, multicenter, real life study carried out in Italy from March 11th to December 11th 2020 during COVID-19 pandemics, dermatological consultations (in-person and telemedicine) to study the prevalence of Koebner (KB) phenomenon due to masks were evaluated. Boyd and Nelder classification was adopted for Koebner phenomenon and Bizzozero's for KB intensity. A total of 229/873 (26.2%) dermatological consultations were KB triggered dermatoses and lesions were located in mask-covered ear area (76 [33.2%]), malar area (73 [31.8%]), perioral area (53 [23.1%]), and nose (27 [11.8%]). The first KB category grouped 142 patients (psoriasis, vitiligo, maskne, and mask rosacea), the second one 24 (warts, molluscum contagiosum, and impetigo), the third one 46 (atopic dermatitis), and the fourth one 17 (eczema). Among previously KB negative psoriatic patients that became KB positive, 9/13 (69.2%) had discontinued or modified the prescribed antipsoriatic treatment. Mask-related Koebner phenomenon is an important clinical sign to orient clinician's therapeutic protocols during COVID-19 pandemic, especially in patients with psoriasis.

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 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.

The PCOS Patients differ in Lipid Profile According to their Phenotypes.

Polycystic ovary syndrome (PCOS) affects 4-18% of women of reproductive age. The number of reports exploring the lipid profiles among PCOS patients and number of studied patients are limited. The aim of our study was to assess the lipid profile separately in lean and non-lean women with polycystic ovary syndrome divided according to hyperandrogenemia, defined as free androgen index (FAI)≥5. The second aim was to compare the lipid profiles among lean and non-lean PCOS patients with respect to hyperandrogenemia and regularity of menstruation cycles. We evaluated 232 patients from Department of Endocrinological Gynecology, Jagiellonian University Medical College in Krakow diagnosed with PCOS. The population consisted of 166 lean and 66 non-lean women. We observed higher levels of total cholesterol, high-density lipoprotein cholesterol (HDL-C) in lean patients with FAI<5 than in lean patients with FAI≥5. There were no differences in lipid profile between non-lean patients with FAI≥5 and non-lean patients with FAI<5. Among lean patients higher total cholesterol levels were observed in those with irregular menstruation cycles and FAI<5 than in patients with FAI≥5 and regular cycles. There were no differences in lipid profiles between four phenotypes among non-lean PCOS patients. CONCLUSIONS: The results of our study showed differences in lipid profile between lean PCOS patients according to their phenotype based on androgens' level. This effect was abandoned by fat tissue mass in non-lean ones. Further studies should be conducted to explore these associations.

Primary cutaneous lymphomas: the analysis of cases treated in the Department of Dermatology University Hospital in Krakow.

Introduction: Primary cutaneous lymphomas are lymphoproliferative skin infiltrates of T-, B- or NK-cells, classified according to the World Health Organization - European Organization of the Research and Treatment of Cancer (WHO-EORTC) criteria. They are the second most common group of extranodal non-Hodgkin lymphomas, that present in the skin with no evidence of systemic involvement at the time of diagnosis. Aims: The aim of the study was the analysis of clinical profile of cutaneous lymphomas in the tertiary referral center in Poland. Material and Methods: We analyzed case records of 63 patients (26 women, 37 men aged 19 - 86) referred to the Department of Dermatology, University Hospital in Cracow for the diagnosis and treatment of cutaneous lymphoma. Results: After analysis of clinical and histological data, the final diagnoses were: mycosis fungoides (42 patients), primary cutaneous CD30+ lymphoproliferative disorder (7), Sezary syndrome (3), parapsoriasis (3), primary cutaneous B-cell lymphoma (1), acute myeloid leukemia (1), Hodgkin lymphoma coexistent with mycosis fungoides (1), generalized allergic contact dermatitis (2) and erythema elevatum diutinum (1). We excluded 2 patients due to incomplete data. The most common location of skin lesions was the lower limb (52.46%) and most common clinical presentation was raised erythematous lesion (26.23%). Pruritus was present in 45.9% of the patients and 39.3% had extracutaneous symptoms, with lymphadenopathy as the most common symptom. 37.7% of patients presented with mild eosinophilia and another 37.7% with mild monocytosis. Prior to referral to our center, general practitioners misdiagnosed the lymphomas commonly as: atopic and contact dermatitis, borreliosis, drug-induced exanthema. Conclusions: The diagnosis of cutaneous lymphoma is often delayed due to their indolent, often recurring course, non-specific symptoms and uncommon appearance. The cooperation of a clinician and pathologist is essential in the diagnostic process.

The role of focal infections in the pathogenesis of psoriasis and chronic urticaria.

INTRODUCTION: The Focal Infection Theory, originally presented at the beginning of the 20(th) century, postulates that systemic diseases can be caused by microorganisms that arise from the focus of infection. Foci of infections have been described as sinuses, adenoids, tonsils, teeth, genitourinary tract, gall bladder and kidneys. A focus of infection is defined as the area that can occur in any part of the body, contains a pathogen (microorganism) and is usually asymptomatic. There are discordant opinions about the role of focal infections in the pathogenesis of psoriasis and urticaria. AIM: To establish whether there is a higher incidence of focal infections in patients with chronic urticaria and psoriasis. MATERIAL AND METHODS: We retrospectively reviewed 129 patients with a history of psoriasis and chronic urticaria: 58 women and 71 men treated in the Department of Dermatology of the Jagiellonian University Medical College in Krakow. RESULTS: In the analyzed group, 11 patients had a dental consultation, 58 - laryngological consultation and 29 women had a gynecological consultation. The most common examples of focal infection were tonsillitis, upper respiratory tract infections, sinusitis, dental caries and genitourinary tract infections. Aggravating factors were similar to previously described. CONCLUSIONS: A high incidence of focal infections in patients with psoriasis and urticaria suggests that infections may play a significant role in the pathogenesis of these skin disorders. Treatment of infection foci may play the key role in the remission of skin changes.

[The role of thyroid antibodies in the pathogenesis of the infertility and miscarriage]. / Rola przeciwcial przeciwtarczycowych w potencjalnej przyczynie nieplodnosci i poronien.

There are discordant opinions about the influence of subclinical hypothyroidism to the fertility of the women. No unequivocal opinion has been presented concerning the purposefulness of the diagnostics process and treatment of the pregnant women with subclinical hypothyroidism. Few clinical studies suggest that there is a connection between thyroid antibodies and infertility, spontaneous miscarriages, implantation failures and fetal malformations.