The efficacy of antimalarial drugs in the therapy of selected forms of cicatricial alopecia.

INTRODUCTION: Frontal fibrosing alopecia (FFA) is primary lymphocytic cicatricial alopecia with a clinically characteristic progressive recession of the frontotemporal hairline, perifollicular erythema, as well as symptoms of itching and burning. It occurs mainly in postmenopausal women. FFA is considered as a subtype of lichen planopilaris (LPP). The treatment of those diseases is presently empirical. AIM: To define the efficacy of treating FFA and LPP with hydroxychloroquine. MATERIAL AND METHODS: We performed a retrospective analysis of 95 women, including 35 with FFA and 60 with LPP. We collected the relevant demographic and clinical data. The response to treatment with hydroxychloroquine was assessed using LPPAI. Also, adverse events were monitored. RESULTS: Treatment with hydroxychloroquine has a statistically significant effect on decreasing the disease activity after 6 and 12 months of therapy. The results of statistical tests do not confirm the existence of a relationship between age range and treatment efficacy. However, there is a correlation between the duration and efficacy of treatment (p < 0.05). CONCLUSIONS: Administration of hydroxychloroquine can be considered as one of the treatment methods for FFA and LPP in everyday clinical practice. The presented study is the first attempt at using hydroxychloroquine to treat such large patient groups for FFA and LPP. Hydroxychloroquine efficaciously alleviates the symptoms in LPP patients and gives maximum benefits in long-term therapy (12 months). The preliminary results obtained in the presented retrospective analysis should be confirmed in a randomized prospective clinical trial, which remains a future challenge for researchers.

Factors affecting the concentration of soluble tumour necrosis factor-α receptor type I in the blood serum of patients with localized scleroderma.

AIM: The aim of the study was to assess of sTNFαR1 concentration in the serum of patients with localized scleroderma (in comparison with a control group). MATERIAL AND METHODS: This was a prospective study. The patients with localized scleroderma were divided into two groups: 21 persons treated with PUVA therapy and 20 persons treated with procaine penicillin. In the case of the patients treated with intramuscularly administered procaine penicillin (dose: 2,400,000 IU/day), achievement of a total dose of at least 30 million IU/day was considered as the end of the therapy. In the group of patients treated with photochemotherapy, the single initial dose during a PUVA session was 0.5 J/cm2 and it was increased by 0.5 J/cm2 every other day to reach the maximum value of 10 J/cm2, depending on the clinical condition. The study involved three sessions a week. RESULTS: sTNFαR1 concentration in the serum of patients with localized scleroderma was significantly higher in comparison with the control group and correlated with the skin damage index. The difference in the determined particle level was higher in the group of patients undergoing photochemotherapy (median: 106.25 ng/ml) than in the group taking penicillin (median: 81.50 ng/ml). Patients treated with PUVA sessions demonstrated a greater decrease in sTNFαR1 concentration and an improvement of the clinical condition after therapy completion. CONCLUSIONS: The obtained results suggest a potential role of sTNFαR1 in the pathogenesis of localized scleroderma.

Does adiponectin play a role in the pathogenesis of chronic spontaneous urticaria?

INTRODUCTION: Chronic spontaneous urticaria constitutes an interdisciplinary problem and its pathogenesis is still a subject of debate. Overweight and hyperlipidemia are supposed to be related to chronic spontaneous urticaria. Fatty tissue can be the source of adipokines. AIM OF THE STUDY: To assess the potential role of adiponectin in chronic spontaneous urticaria pathogenesis. MATERIAL AND METHODS: The study included 52 chronic spontaneous urticaria patients and 43 healthy controls. The patients were divided into two subgroups: patients with wheals only, and patients with urticaria and an accompanying angioedema. The adiponectin concentration was measured in all studied subjects. RESULTS: No statistically significant difference in adiponectin level was determined between the studied groups and subgroups. CONCLUSIONS: We are among the first to present the results of study to determine a possible role of adipokines in chronic spontaneous urticaria pathogenesis. We did not observe any difference in adiponectin level. In our opinion, it is necessary to conduct further analyses in this field.

Are new variants of psoriasis therapy (IL-17 inhibitors) safe?

Psoriasis is a chronic, recurrent, inflammatory, and proliferative skin disease. Its etiology has not yet been fully assessed, but undoubtedly it is a multifaceted disease. The key role in its pathomechanism is played by genetic, immunologic, and environmental factors and stress. If traditional methods of psoriasis treatment (phototherapy, methotrexate, retinoids, cyclosporine A) fail, we reach for the following biopharmaceuticals - infliximab, etanercept, adalimumab, or ustekinumab. However, genetic engineering progress discovers new possibilities - the pending clinical trials involve IL-17, IL-23 antagonists, PDE4 and -3 and -1. Psoriasis etiopathogenesis mainly involves the IL-17A, IL-17F, and IL-17A/F subtypes, which affect the keratinocytes. The biological therapy molecularly oriented with the antagonists of interleukin 17 is based mainly on the influence onto the cytokine in the manner that prevents it from binding with the receptor. Three biopharmaceuticals are currently under third phase studies: two fully humanized antibodies neutralizing IL-17 - ixekizumab and secukinumab, and one human monoclonal antibody, brodalumab. The below work will be devoted to the analysis of possible undesirable symptoms, which were observed during the studies. We will try to review the latest literature concerning the most important clinical trials conducted in many centers.

Newer treatments of psoriasis regarding IL-23 inhibitors, phosphodiesterase 4 inhibitors, and Janus kinase inhibitors.

The rapid progress of genetic engineering furthermore opens up new prospects in the therapy of this difficult-to-treat disease. IL-23 inhibitors, phosphodiesterase 4 (PDE4) inhibitors, and Janus kinase (JAK) inhibitors are currently encouraging further research. Two drugs which are IL-23 inhibitors are now in phase III of clinical trials. The aim of the action of both drugs is selective IL-23 inhibition by targeting the p19 subunit. Guselkumab is a fully human monoclonal antibody. Tildrakizumab is a humanized monoclonal antibody, which also belongs to IgG class and is targeted to subunit p19 of interleukin 23 (IL-23). Phosphodiesterase inhibitors exert an anti-inflammatory action and their most common group is the PDE4 family. PDE4 inhibits cAMP, which reduces the inflammatory response of the pathway of Th helper lymphocytes, Th17, and type 1 interferon which modulates the production of anti-inflammatory cytokines such as IL-10 interleukins. The Janus kinase (JAK) signaling pathway plays an important role in the immunopathogenesis of psoriasis. Tofacitinib suppresses the expression of IL-23, IL-17A, IL-17F, and IL-22 receptors during the stimulation of lymphocytes. Ruxolitinib is a selective inhibitor of JAK1 and JAK2 kinases and the JAK-STAT signaling pathway. This article is a review of the aforementioned drugs as described in the latest available literature.

Pregnancy: a therapeutic dilemma.

Treatment during pregnancy is problematic. The Food and Drug Administration established drug categories to help in the treatment process. First-generation antihistamines are considered safe but they have sedative properties. Second-generation antihistamines cause less adverse reactions but besides cetirizine and loratadine they belong to category C. All retinoids should be avoided during pregnancy due to the risk of fetal malformations. Antimalarial drugs should be considered based on the clinical data. Sulfones can be considered as safe for use during pregnancy only with proper monitoring. Prednisone is administered in pregnancy. Other glucocorticosteroids have a different safety profile. Cyclosporine A treatment should be reserved as rescue therapy in severe stages of the disease. Treatment during pregnancy should be precise when it comes to pregnant woman and safe for the fetus.

TNF-α in a molecularly targeted therapy of psoriasis and psoriatic arthritis.

Psoriasis is a chronic immunological skin disease and patients with this disorder typically experience a significant decrease in their quality of life. The disease is traditionally managed with topical and systemic agents (retinoids, ciclosporin A, methotrexate), but these treatment options are often long-term and their effects can be inconsistent and not ideal. The use of biological drugs in dermatological treatment is relatively new and began in the early 2000s. It should be noted that, in most countries, in order for biological treatment to be administered, specific criteria must be met. The current treatment options for psoriasis and psoriatic arthritis include tumour necrosis factor alpha (TNF-α) blockers, interleukin (IL)-12 and IL-23 inhibitors, T cell inhibitors and B cell inhibitors. These classes of biological drugs are characterised by protein structure as well as high molecular weight and their effectiveness is evaluated based on the Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA) and the Dermatology Life Quality Index (DLQI). TNF-α antagonists are one such class of biological drugs which includes infliximad, etanercept and adalimumab. Infliximab is a chimeric protein that is administered via intravenous infusions as a monotherapy in psoriasis vulgaris. Etanercept is indicated for use in both psoriasis vulgaris and psoriatic arthritis and it is the only drug that can be used as a treatment for children under the age of 8 with psoriasis. The drug is administered subcutaneously. Finally, adalimumab is a fully human monoclonal antibody that neutralises both free and membrane-bound TNF-α and is used in the treatment of psoriasis vulgaris and psoriatic arthritis. This article reviews the latest research in the use of TNF-α for the treatment of moderate to severe psoriasis and psoriatic arthritis. The results of research in this field are promising and confirm the effectiveness and safety of biological drugs as dermatological treatments for psoriasis. In particular, adalimumab, etanercept and infliximab are promising therapeutic options for patients with moderate to severe psoriasis and psoriatic arthritis who are unresponsive to conventional treatment strategies and they can significantly improve the quality of lives in patients with this disease.