Fitzpatrickʼs Dermatology in General Medicine

Andrews' diseases of the skin, clinical dermatology

Itch (or pruritus) was not previously recognized as a serious symptom of psoriasis. However, approximately 60–90% of psoriatic patients with pruritus have stated that it deteriorates their quality of life. Since conventional antipruritic therapies, such as antihistamines, only exert limited effects, the establishment of a treatment option for itch in psoriasis is urgently needed. Although a definitive drug is not currently available, various itch mediators are known to be involved in pruritus in psoriasis. In this review, we describe the clinical features of pruritus in psoriasis, classify a wide range of itch mediators into categories, such as the nervous, immune, endocrine, and vascular systems, and discuss the mechanisms by which these mediators induce or aggravate itch in the pathophysiology of psoriasis.

https://www.mdpi.com/1422-0067/21/21/8406/pdf

Molecular and Cellular Mechanisms of Itch in Psoriasis.

Thymic Stromal Lymphopoietin (TSLP) and Interleukin-7 (IL-7) are widely studied cytokines within distinct branches of immunology. On one hand, TSLP is crucially important for mediating type 2 immunity at barrier surfaces and has been linked to widespread allergic and inflammatory diseases of the airways, skin, and gut. On the other hand, IL-7 operates at the foundations of T-cell and innate lymphoid cell (ILC) development and homeostasis and has been associated with cancer. Yet, TSLP and IL-7 are united by key commonalities in their structure and the structural basis of the receptor assemblies they mediate to initiate cellular signaling, in particular their cross-utilization of IL-7Rα. As therapeutic targeting of TSLP and IL-7 via diverse approaches is reaching advanced stages and in light of the plethora of mechanistic and structural data on receptor signaling mediated by the two cytokines, the time is ripe to provide integrated views of such knowledge. Here, we first discuss the major pathophysiological roles of TSLP and IL-7 in autoimmune diseases, inflammation and cancer. Subsequently, we curate structural and mechanistic knowledge about receptor assemblies mediated by the two cytokines. Finally, we review therapeutic avenues targeting TSLP and IL-7 signaling. We envision that such integrated view of the mechanism, structure, and modulation of signaling assemblies mediated by TSLP and IL-7 will enhance and fine-tune the development of more effective and selective approaches to further interrogate the role of TSLP and IL-7 in physiology and disease.

https://biblio.ugent.be/publication/8672946/file/8673302.pdf

Modulation of Signaling Mediated by TSLP and IL-7 in Inflammation, Autoimmune Diseases, and Cancer.

Translational pathology, genomics and the development of systemic therapies for acral melanoma.

Cutaneous tuberculosis (TB) has several clinical manifestations. The most common forms include cervical scrofuloderma and plaque type of lupus vulgaris (LV), otherwise the rare cases including inguinal scrofuloderma, ulcerative LV, and acute miliary TB. The highlight of this case series was to report various rare clinical manifestations of cutaneous TB.

Various cutaneous tuberculosis with rare clinical manifestations: A case series.

Background: Rifampicin is one of the important components in the multidrug therapy (MDT)-World Health Organization regimen for leprosy. Clarithromycin is one of the alternative therapies of rifampicin. Methods: This clinical pilot study was to compare the efficacy of 2,000 mg clarithromycin to 600 mg rifampicin in combination with dapsone and clofazimine for 3 months in multibacillary (MB) leprosy patients. They were divided into an MDT-MB regimen group that consists of rifampicin-dapsone-clofazimine and clarithromycin-dapsone-clofazimine (CDC) regimen group, each group consisted of seven patients. Results: The morphological index (MI) was reduced insignificantly after 3 months therapy in MDT-MB group (P = 0.248). While in the CDC group, the MI decrement showed a significant result (P = 0.004). The comparison of MI reduction in MDT-MB and CDC groups showed an insignificant difference (P = 0.130). Skin discoloration was occurred in both groups, whereas mild-nausea was presented in the CDC group, in addition, red-colored urine was developed in the MDT-MB group. Conclusion: We concluded that 2,000 mg clarithromycin is as effective as 600 mg rifampicin in combination with dapsone and clofazimine regimen in MB leprosy patients. Hence, clarithromycin can be considered as an alternative therapy for leprosy patients who resistance and/or allergy to rifampicin.

Clinical pilot study: Clarithromycin efficacy in multibacillary leprosy therapy.

Thymic stromal lymphopoietin (TSLP) is known to be associated with allergic diseases. It is also suggested that TSLP has a role in autoimmune diseases such as psoriasis; however, the associated pathways remain unknown. There is currently little information on TSLP in psoriasis vulgaris. We investigated TSLP expressions on lesional and non-lesional skin of psoriasis vulgaris patients using reverse transcription- polymerase chain reaction. TSLP level was also investigated in serum from psoriasis vulgaris patients compared to healthy control using enzyme-linked immunosorbent assay. TSLP expression was higher in lesional skin (1.90) compared to non-lesional skin (1.76); however, the difference was not statistically significant (P>0.05). TSLP serum levels were significantly higher in psoriasis patients (287.40 pg/dL) as compared to controls (114.70 pg/dL) (P<0.05). This study concluded that TSLP levels in the serum of psoriasis vulgaris patients are higher than controls. TSLP was also found in keratinocyte of psoriasis patients, the expression was higher in the lesional compared to non-lesional skin; however, this difference is statistically insignificant. These findings suggest that TSLP may play a role in the pathogenesis of psoriasis vulgaris, but its exact role remains unclear.

/pdf/skin-tissue-expression-and-serum-level-of-thymic-stromal-nvc3ssxfzm.pdf

Skin tissue expression and serum level of thymic stromal lymphopoietin in patients with psoriasis vulgaris.

BACKGROUND The tumor microenvironment including immune surveillance affects malignant melanoma (MM) behavior. Nuclear factor κB (NF-κB) stimulates the transcription of various genes in the nucleus and plays a role in the inflammatory process and in tumorigenesis. CD8+ T cells have cytotoxic properties important in the elimination of tumors. However, inhibitory receptors on the cell surface will bind to programmed death-ligand 1 (PD-L1), causing CD8+ T cells to lose their ability to initiate an immune response. This study analyzed the association of NF-κB and PD-L1 expression levels and CD8+ T-cell counts with depth of invasion of acral MM, which may be a predictor of aggressiveness related to an increased risk of metastasis. METHODS A retrospective cross-sectional study was conducted in the Department of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital using 96 cases of acral melanoma. Immunohistochemical staining was performed on paraffin blocks using anti-NF-κB, -PD-L1, and -CD8 antibodies and invasion depth was measured using dotSlide-imaging software. RESULTS The study showed significant associations between the individual expression of NF-κB and PD-L1 and CD8+ T-cell number, with MM invasion depth. NF-κB was found to be a confounding variable of CD8+ T-cell number (p < .05), but not for PD-L1 expression (p = .154). Through multivariate analysis it was found that NF-κB had the greatest association with the depth of invasion (p < .001), whereas PD-L1 was unrelated to the depth of invasion because it depends on the number of CD8+ T cells (p = .870). CONCLUSIONS NF-κB plays a major role in acral MM invasion, by decreasing the number of CD8+ T cells in acral MM.

http://www.jpatholtm.org/upload/pdf/jptm-2018-04-04.pdf

The Major Role of NF-κB in the Depth of Invasion on Acral Melanoma by Decreasing CD8+ T Cells.

Multifocal tuberculosis (TB) is rare. The risk of occurrence of multifocal TB is increasing in immunocompromised patients. Cutaneous entanglement in multifocal TB occurs more infrequently, and its association with multifocal TB is scarcely reported. The aim of this case report was to show a rare case of lupus vulgaris accompanied by multifocal skeletal TB (vertebrae and knee joint) in a 15-year-old girl. There were kyphosis and deformities seen on physical examination. Dermatological status showed an erythematous plaque on the cheek and an erythematous nodule on the index finger of the left hand. The additional examinations such as bacteriological, histopathological, and polymerase chain reaction (PCR) examinations supported the diagnosis of cutaneous TB. Radiographic and PCR examinations confirmed the diagnosis of multiple skeletal TB. Mycobacterium tuberculosis was obtained from GeneXpert® examination of the skin lesion on the right cheek and synovial fluid of the knee. Therefore, multifocal TB could be confirmed in this patient. The uncommonness of the skin involvement in TB infection should warn the clinicians to commit every possible examination to detect the TB involvement in other organs, especially in immunocompromised children with suspected skin lesions.

Reti Hindritiani

Papers

Various cutaneous tuberculosis with rare clinical manifestations: A case series.

Clinical pilot study: Clarithromycin efficacy in multibacillary leprosy therapy.

Skin tissue expression and serum level of thymic stromal lymphopoietin in patients with psoriasis vulgaris.

The Major Role of NF-κB in the Depth of Invasion on Acral Melanoma by Decreasing CD8+ T Cells.

A rare case of multiple lupus vulgaris in a multifocal tuberculosis pediatric patient.