Immunohistochemical Study of the PD-1/PD-L1 Pathway in Cutaneous Lupus Erythematosus

The pathomechanism of various autoimmune diseases is known to be associated with the altered function of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) axis. We aimed to investigate the role of this pathway and inflammatory cell markers in subtypes of cutaneous lupus erythematosus (CLE): discoid lupus erythematosus (DLE), subacute CLE (SCLE) and toxic epidermal necrolysis (TEN)-like lupus, a hyperacute form of acute CLE (ACLE). Ten skin biopsy samples from 9 patients were analyzed with immunohistochemistry regarding the following markers: CD3, CD4, CD8, Granzyme B, CD123, CD163, PD-1, PD-L1. Our group consisted of 4 SCLE (2 idiopathic (I-SCLE) and 2 PD-1 inhibitor-induced (DI-SCLE)), 4 DLE and 1 TEN-like lupus cases. From the latter patient two consecutive biopsies were obtained 1 week apart. Marker expression patterns were compared through descriptive analysis. Higher median keratinocyte (KC) PD-L1 expression was observed in the SCLE group compared to the DLE group (65% and 5%, respectively). Medians of dermal CD4, Granzyme B (GB), PD-1 positive cell numbers and GB+/CD8+ ratio were higher in the DLE group than in the SCLE group. The I-SCLE and DISCLE cases showed many similarities, however KC PD-L1 expression and dermal GB positive cell number was higher in the former. The consecutive samples of the TEN-like lupus patient showed an increase by time within the number of infiltrating GB+ cytotoxic T-cells and KC PD-L1 expression (from 22 to 43 and 30%–70%, respectively). Alterations of the PD-1/PD-L1 axis seems to play a role in the pathogenesis of CLE

Lymphomatoid papulosis type B in a patient with Crohn\u27s disease treated with TNF-alpha inhibitors infliximab and adalimumab

No abstract availabl

Visualization of keratin with diffuse reflectance and autofluorescence imaging and nonlinear optical microscopy in a rare keratinopathic ichthyosis

Funding Information: Funding: This work was supported by grants from the National Research, Development and Innovation Office of Hungary—NKFIH (FK_131916, 2019 (Semmelweis University, M.M.)), EFOP-3.6.3-VEKOP-16-2017-00009 (P.A., S.B.); the New National Excellence Program of the Ministry for Innovation and Technology (ÚNKP-20-4-II-SE-7 (N.K.), ÚNKP-19-3-I-SE-78 (L.F.)); and the European Regional Development Fund project “Time-resolved autofluorescence methodology for noninvasive skin cancer diagnostics” (no. 1.1.1.2/16/I/001, agreement no. 1.1.1.2/VIAA/1/16/014 (I.L., A.L., M.L.)). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Keratins are one of the main fluorophores of the skin. Keratinization disorders can lead to alterations in the optical properties of the skin. We set out to investigate a rare form of keratinopathic ichthyosis caused by KRT1 mutation with two different optical imaging methods. We used a newly developed light emitting diode (LED) based device to analyze autofluorescence signal at 405 nm excitation and diffuse reflectance at 526 nm in vivo. Mean autofluorescence intensity of the hyperkeratotic palmar skin was markedly higher in comparison to the healthy control (162.35 vs. 51.14). To further assess the skin status, we examined samples from affected skin areas ex vivo by nonlinear optical microscopy. Two-photon excited fluorescence and second-harmonic generation can visualize epidermal keratin and dermal collagen, respectively. We were able to visualize the structure of the epidermis and other skin changes caused by abnormal keratin formation. Taken together, we were able to show that such imaging modalities are useful for the diagnosis and follow-up of keratinopathic diseases.publishersversionPeer reviewe

A lupus erythematosus panniculitis lefolyásának jellegzetességei 17 betegünk retrospektív vizsgálata alapján

Bevezetés: A lupus erythematosus panniculitis (LEP) a cutan lupus erythematosus krónikus formájának ritka variánsa, klinikailag tömött, subcutan csomók és erythemás plakkok jellemzik. Az aktív tünetek az arcot és testet torzító ma- radványtünetekkel gyógyulhatnak, rontva a betegek életminőségét. A szisztémás lupus erythematosus (SLE) részjelensége lehet, első tüneteként is kialakulhat. Célkitűzés: A LEP klinikopatológiai képének bemutatása saját beteganyagunk szemléltetésével, a betegség lefolyásá- nak értékelése. Módszerek: A Semmelweis Egyetem Bőr-, Nemikórtani és Bőronkológiai Klinikáján 2000 és 2022 között jelentkezett LEP-betegek összegyűjtése, adataik retrospektív elemzése. Eredmények: A 17 beteg közül 1 férfi, 16 nő, átlagéletkoruk 37,8 év volt. Tüneteik a leggyakrabban a proximalis alsó és felső végtagokon jelentkeztek (alsó: 8/17, felső: 7/17), az arc 4, az emlő 3, a mellkas és a farpofák 2-2, a hát és a lábszár 1-1 esetben volt érintett. A leggyakrabban aktív csomó (11/17), illetve plakk jelentkezett (7/17), 4 esetben lipoatrophia, 3-nál kifekélyesedés, 1-nél kalcifikáció. 6 betegnél a subcutan tünetet discoid plakk fedte. 10 betegnél alakult ki szisztémás tünet: arthritis (4/17), hematológiai eltérés (5/17), veseérintettség (2/17), antifoszfolipid- szindróma (2/17). Az SLE diagnózisát 7 esetben tudtuk felállítani. A szövettani kép 8 esetben kevert típusú panni- culitist, 3-nál lobularist mutatott. Átlagosan 24,3 hónap telt el a diagnózis felállításáig. SLE-s betegeink bőrtünetei regrediáltak az alkalmazott szisztémás immunszuppresszív kezelésekre. A kizárólag bőrmanifesztációt mutató betegeink körében gyakori volt a terápiarezisztencia a cutan lupus erythematosusban alkalmazott kezelésekre. Következtetés: A LEP diagnosztizálása több hónapot, évet vehet igénybe. Szélesebb körű ismerete segítheti a gyorsabb diagnózisalkotást, megelőzhető a maradványtünetek, illetve az esetleges belszervi elváltozások kialakulása. Megfi- gyeléseink alapján SLE nélküli LEP esetén is korai immunszuppresszív terápiát lenne érdemes bevezetni

Scrofuloderma and granuloma annulare-like lesions: Challenges of diagnosing cutaneous tuberculosis in developed countries

Tuberculosis remains a global health concern, as the increasing levels of urban poverty, higher number of immunodeficient patients and the development of drug resistance threaten the overall efforts made to induce a downward trend for the disease. Scrofuloderma, also known as tuberculosis cutis colliquativa is a subtype of cutaneous tuberculosis. Here we detail a case of a 70-year-old female patient presented with unilateral, left-sided, multiple palpable, painful, ulcerated and purulent cervical nodules, accompanied by persistent generalized erythematous popular granuloma annulare-like skin lesions on the upper extremities. Based on the result of the PCR assay, culture, imaging and histopathological findings, the diagnosis of scrofuloderma was established.To achieve prompt diagnosis and early treatment, it is crucial to include scrofuloderma in the differential diagnosis of ulcerated lesions in developed countries as well, and also be aware of the additional clinical symptoms, such as granuloma annulare-like lesions, possibly accompanying cutaneous tuberculosis

Cutaneous malignancies in patients with Parkinson’s disease at a dermato-oncological university centre in Hungary

BackgroundThe possible correlation between melanoma and Parkinson’s disease (PD) has been intensively studied. In this work, we aimed to assess the coincidence of skin malignancies and PD at a dermato-oncological university centre in Central-Eastern Europe, Hungary.MethodsFrom 2004 to 2017, a retrospective analysis of the centre’s database was performed based on International Statistical Classification of Diseases-10 codes.ResultsOut of the patients who visited the clinic during the study period, 20,658 were treated for malignant skin tumours. Over the 14 years, 205 dermatological patients had PD simultaneously, 111 (54%) of whom had at least one type of skin malignancy: melanoma (n=22), basal cell carcinoma (BCC) (n=82), or squamous cell carcinoma (SCC) (n=36) (in some patients, multiple skin tumours were identified). Compared to the age- and sex-matched control group, patients with PD had a significantly lower risk for basal cell carcinoma (OR, 0.65; 95% CI, 0.47–0.89, p=0.0076) and for all skin tumours (OR, 0.74; 95% CI, 0.56–0.98, p=0.0392) but not for melanoma.ConclusionsWe found a decreased risk of all skin tumours and basal cell carcinoma and an unchanged risk of melanoma among patients with PD. However, it should be kept in mind that some large-scale meta-analyses suggest a higher incidence of melanoma after a diagnosis of PD, indicating the importance of skin examination in this vulnerable population

Whole genome sequencing resolves 10 years diagnostic odyssey in familiar myxoma

Abstract Carney complex (CNC) is an ultrarare disorder causing cutaneous and cardiac myxomas, primary pigmented nodular adrenocortical disease, hypophyseal adenoma, and gonadal tumours. Genetic alterations are often missed under routine genetic testing. Pathogenic variants in PRKAR1A are identified in most cases, while large exonic or chromosomal deletions have only been reported in a few cases. Our aim was to identify the causal genetic alteration in our kindred with a clinical diagnosis of CNC and prove its pathogenic role by functional investigation. Targeted testing of PRKAR1A gene, whole exome and whole genome sequencing (WGS) were performed in the proband, one clinically affected and one unaffected relative. WGS identified a novel, large, 10,662 bp (10.6 kbp; LRG_514t1:c.-10403_-7 + 265del; hg19, chr17:g.66498293_66508954del) deletion in the promoter of PRKAR1A in heterozygous form in the affected family members. The exact breakpoints and the increased enzyme activity in deletion carriers compared to wild type carrier were proved. Segregation analysis and functional evaluation of PKA activity confirmed the pathogenic role of this alteration. A novel deletion upstream of the PRKAR1A gene was proved to be the cause of CNC. Our study underlines the need for WGS in molecular genetic testing of patients with monogenic disorders where conventional genetic analysis fails