Cutaneous, systemic features and laboratory characteristics of late- versus adult-onset systemic lupus erythematosus in 1006 Thai patients

Background Age at disease onset may modulate systemic lupus erythematosus (SLE), but its relation to cutaneous/extracutaneous manifestation remains understudied. Objective To compare the cutaneous, systemic features, laboratory characteristics, and disease severity between late- and adult-onset SLE patients Methods Analyses of the cutaneous, systemic involvement, laboratory investigations, SLE disease activity index 2000 (SLEDAI-2K), and disease damage were performed to compare between groups. Results Of 1006 SLE patients, 740 and 226 had adult- (15–50 years) and late-onset (>50 years), respectively. Among 782 with cutaneous lupus erythematosus (CLE), acute CLE (ACLE) and chronic CLE (CCLE) were more common in the adult- and late-onset SLE, respectively ( p = 0.001). Multivariable logistic regression analysis demonstrated that male patients and skin signs, including papulosquamous subacute CLE, discoid lupus erythematosus, and lupus profundus, were associated with late-onset SLE (all p < 0.05). Late-onset SLE had lower lupus-associated autoantibodies, and systemic involvement (all p < 0.05). ACLE, CCLE, mucosal lupus, alopecia, and non-specific lupus were related to higher disease activity in adult-onset SLE (all p < 0.001). There was no difference in the damage index between the two groups. Conclusions Late-onset SLE had a distinct disease expression with male predominance, milder disease activity, and lower systemic involvement. Cutaneous manifestations may hold prognostic values for SLE.

Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart

Lyme carditis is an extracutaneous manifestation of Lyme disease characterized by episodes of atrioventricular block of varying degrees and additional, less reported cardiomyopathies. The molecular changes associated with the response to Borrelia burgdorferi over the course of infection are poorly understood. Here, we identify broad transcriptomic and proteomic changes in the heart during infection that reveal a profound down-regulation of mitochondrial components. We also describe the long-term functional modulation of macrophages exposed to live bacteria, characterized by an augmented glycolytic output, increased spirochetal binding and internalization, and reduced inflammatory responses. In vitro, glycolysis inhibition reduces the production of tumor necrosis factor (TNF) by memory macrophages, whereas in vivo, it produces the reversion of the memory phenotype, the recovery of tissue mitochondrial components, and decreased inflammation and spirochetal burdens. These results show that B. burgdorferi induces long-term, memory-like responses in macrophages with tissue-wide consequences that are amenable to be manipulated in vivo.

Novel Therapeutic Approaches and Treatment Targets for Psoriatic Arthritis

Background: Psoriatic Arthritis (PsA) is the most common extracutaneous manifestation of psoriasis. This chronic inflammatory arthritis is burdened with significant morbidity, leading to irreversible joint damage and disability. In recent years, a deeper understating of its pathogenesis has led to the development of several new drugs targeting different pathways. Objectives: This review aims to highlight the clinical efficacy and safety of the novel agents that have become recently available for the treatment of PsA, as well as new promising therapeutic targets that are being evaluated in clinical trials. Methods: For the purpose of this narrative review, we searched in the MEDLINE and ClinicalTrials. gov databases. Results: After the introduction of the first biological drugs targeting Tumor Necrosis Factor (TNF), several other drugs with different targets have been developed, including anti-Interleukin (IL) 12/23p40, anti-IL17, and, more recently, anti-IL23p19 agents. Conclusions: Data supporting the efficacy of different agents in the major domains of PsA, as well as their safety issues, are summarized here. Finally, the current pipeline, including several novel nonbiological small molecules, such as Janus kinase (JAK) inhibitors, that are currently being evaluated in clinical trials are also presented. Discussion: The availability of newer therapeutic agents has substantially changed the treatment strategy for PsA. In the future, a personalized treatment approach will probably achieve better control of disease manifestations.

Prognostic markers of mycosis fungoides by means of two cases

Cutaneous T-cell lymphoma is a heterogeneous group of malignancies including both indolent and aggressive forms, with an average 5-year disease-specific survival rate of 11-100%. Prognostic factors in cutaneous T-cell lymphoma according to the different subtypes are not clearly defined, however extracutaneous manifestation seems to predict a poor prognosis. Tonsil involvement was revealed as a cause of oropharyngeal complaints in two of our male patients, treated for histologically confirmed tumour stage of mycosis fungoides. In the first case urgent tracheostomy followed by radiotherapy, while in the other case systemic treatment resulted in complete remission of the tonsil involvement. Both patients were subsequently lost due to the progression of mycosis fungoides. Factors predicting an unfavourable prognosis included extracutaneous manifestation, late stage disease, age over 60 years, elevated lactate-dehydrogenase levels, and large cell transformation. With our cases we would like to shed light to the prognostic markers of mycosis fungoides, and to the rare tonsil involvement, which is potentially life-threatening and requires urgent intervention.

Large B - Cell Lymphoma of the Leg – Unfavourable Course with Rituximab/Bendamustin

BACKGROUND: Cutaneous B-cell lymphomas represent about 25% of all cutaneous lymphomas. Peripheral diffuse large B-cell lymphoma of the leg type is the most aggressive subtype seen mainly in elderly patients. Treatment is not standardised. CASE REPORT: An 87-year-old female patient was presented in May 2018 because of the development of painless subcutaneous nodules on the legs since late 2017. On examination, we observed up to 5 cm large erythematous nodules on the legs and a smaller plaque in the left submammary fold. The histology of a skin demonstrated tumour infiltrate that was separated from the overlying epidermis by a grenz zone. It consisted of densely packed, blastoid lymphocytic cells with numerous, and some atypical mitoses. The cells were positive for CD20, CD79A and CD5. Almost 100% of the cells were labelled with Ki67. The diagnosis of a diffuse large B-cell lymphoma (PCLBCL-LT) of the leg was confirmed. Histologic analysis of a bone marrow biopsy demonstrated a hypercellular bone marrow without malignant lymphatic infiltrates. Diagnostic ultrasound of cervical nodes and computerised tomography (CT) scans (native and with contrast medium) of head, neck and trunk excluded an extracutaneous manifestation of the PCLBCL-LT. Treatment with rituximab plus bendamustibe was initiated, but tumour progress was noted after the second course. Suggested palliative therapy with radiation and rituximab was refused. The patient died 7 months after diagnosis. CONCLUSIONS: Although some trials suggested a beneficial effect of immuno-chemotherapy, the prognosis of (PCLBCL-LT) remains poor. Standardised treatment is missing due to the relative rarity of this malignancy.

Screening of Patients with Psoriasis for Psoriatic Arthritis in the Slovak Republic

Global prevalence of psoriasis is ranging from 0.91 % to 8.5 % [1]. Exact numbers are missing for Slovakia. 1-5% range is the most probable while 2 % is also mentioned as an average prevalence for the European population. There is approximately 110 thousand patients suffering from psoriasis when extrapolating from total population of 5.5 million [2]. Extracutaneous manifestation is observed in 11–30 % of patients after years of solely skin symptoms presentation [3, 4, 5, 6].Objective: To estimate prevalence of psoriatic arthritis among psoriatic patients population visiting dermatology out-patient irrelevant of the disease duration and the treatment regimen. To compare the sensitivity of both tests (ToPAS and PASE) used, evaluate possible PsA risk factors.Methods: This was a prospective, non-interventional, epidemiological, observational study conducted using a survey administered to psoriatic patients by their dermatologists. 10–20 consequent outpatients with psoriasis in each center in 43 regional dermatology officies were screened for the presence of extra-cutaneous symptoms (i.e. joint pain, enthesitis, dactylitis, nail involvement) using questionnaire, developed specificaly for this study, and by the PASE and ToPAS questionnaires. Patients without personal history of PsA and „positivity“ of PASE and/or ToPAS were sent to the center for confirmation / exclusion of the diagnosis by applying CASPAR criteria. Outcomes were statistically processed.Results: 177 (21.8 %) of total of 831 psoriatic patients had PsA. 9 of 177 (5.35 %) has been newly diagnosed. There was almost equal number of men (50.5 %) and women (49.5 %).Plaque psoriasis has been most frequent type – 76.9 %. 43.2 % of PsA patients reported the onset of the disease after 40 years of life. Time interval between onset of psoriasis and PsA has been less than 10 years in 20.2 %, 10–20 years in 20.8 % and more than 20 years in 16.1 %. Most frequent co-morbidity in the study population was hypertension 23.2 %, asthma 3 % and diabetes 2.4 %. Average value of BSA and PASI was higher in PsA vs. non-PsA group: 24 vs. 20 and 10 vs 9, respectively. The sensitivity (72.6 % vs 58.9 %, P=0.01) and specificity (81.3 % vs 80.5 %) of ToPAS was higher compared to PASE.Conclusion: 21.8 % PsA prevalence in psoriatic population in Slovakia is within the range observed in other studies. ToPAS test showed comparable results in terms of specificity, but significantly better results in terms of sensitivity and its early application should be of major importance because of the diagnostic process acceleration. The effect of an early diagnosis on the total patient outcome should be an objective of further research. This project was supported from educational grant of Pfizer Inc.