Pálma Silló

Eosinophilic fasciitis associated with Mycoplasma arginini infection

ABSTRACT Eosinophilic fasciitis (EF) with generalized sclerodermiform skin lesions developed over a 19-month period in a previously healthy 23-year-old man. Although we confirmed EF by skin histology and laboratory tests, the recurrent fevers and the clinical observation of sclerotic prepuce with urethritis indicated further bacteriological analysis by conventional microbiological and DNA-based tests. Urethra cultures were positive for an arginine-hydrolyzing mycoplasma and Ureaplasma urealyticum. The patient also had serum IgM antibodies to Mycoplasma pneumoniae using enzyme-linked immunosorbent assay (ELISA)-based qualitative detection. Mycoplasma arginini was isolated from two independent venous blood serum samples and was identified by conventional microbiological tests and sequencing of the 16S rRNA and rpoB genes (GenBank sequence accession numbers HM179555 and HM179556, respectively). M. arginini genomic DNA also was detected by species-specific PCR in the skin lesion biopsy sample. Treatment with corticosteroids and long-term courses of selected antibiotics led to remission of skin symptoms and normalization of laboratory values. This report provides the first evidence of EF associated with mycoplasma infection and the second report of human infection with M. arginini and therefore suggests that this mycoplasma infection might have contributed to the pathogenesis of the disease.

Rapid systemic and local treatments with the antibacterial peptide dimer A3-APO and its monomeric metabolite eliminate bacteria and reduce inflammation in intradermal lesions infected with Propionibacterium acnes and meticillin-resistant Staphylococcus aureus

When administered intramuscularly, the designer antibacterial peptide dimer A3-APO is highly efficacious in mouse models of Acinetobacter baumannii and Staphylococcus aureus burn infections. Here we compared the efficacy of A3-APO and its monomeric metabolite in mouse models of S. aureus and Propionibacterium acnes intradermal infections following administration as intramuscular (i.m.) or topical treatments. In the animal models, either (i) the ears of CD-1 mice were infected with P. acnes or (ii) S. aureus was injected into burn wounds inflicted to the back. A3-APO or the monomer were injected intramuscularly at 5 mg/kg one to three times or were applied three times as 1% local treatment in phosphate-buffered saline or Vaseline(®). Despite being inactive against the strains in vitro, in vivo the skin conditions of the mice were dramatically improved upon peptide treatment regardless of dosing frequency, administration mode or drug valency. In the P. acnes study, A3-APO statistically significantly reduced ear thickness and ear bacterial counts. The amount of ear connective tissue and epithelial macrophages correlated with therapeutic success. Bacterial load in the lesions was more representative of physical improvement than ear dimensions. In the S. aureus model, both peptides eliminated wound bacteria from >10(7) CFU/mg to almost background levels, with monomer treatment being somewhat more successful. In conclusion, A3-APO and its monomeric metabolite very efficiently ameliorate resistant aerobic and anaerobic intradermal infections, but the protection is apparently not due to direct bacterial killing. Immunostimulatory and anti-inflammatory actions are likely involved. Nevertheless, topical and i.m. administrations are equally effective.

Searching for foreign antigens as possible triggering factors of autoimmunity : Torque Teno virus DNA prevalence is elevated in sera of patients with bullous pemphigoid

Objective:  The Torque Teno virus (TTV), a member of virus genus Anellovirus has been shown to be commonly present in humans, yet without detectable pathogenicity. Recent studies imply that TTV may contribute to provoke autoimmune progresses in systemic lupus erythematosus and idiopathic inflammatory myopathies. We aimed to study the presence of TTV in a group of patients with autoimmune bullous diseases with a further goal to identify long‐lasting foreign antigen, such as TTV as possible triggers of skin‐specific autoimmunity.

Evidence for a role of autoantibodies to heat shock protein 60, 70, and 90 in patients with dermatitis herpetiformis

Heat shock proteins (Hsp) are highly conserved immunomodulatory molecules upregulated when cells are exposed to stressful stimuli, such as inflammation. Their involvement in various autoimmune diseases, including autoimmune bullous diseases and celiac disease, has been increasingly recognized. To further study the role of Hsp in autoimmune bullous diseases, we have investigated for the first time the humoral autoimmune response to Hsp40, Hsp60, Hsp70, and Hsp90 in patients with dermatitis herpetiformis (DH; n = 26), bullous pemphigoid (BP; n = 23), and pemphigus vulgaris (PV; n = 16), the first representing a cutaneous manifestation of celiac disease. While in patients with active BP and PV, serum levels of autoantibodies against these Hsp did not differ from the corresponding age- and gender-matched healthy controls (n = 9–14); circulating autoantibodies against Hsp60, Hsp70, and Hsp90 were found to be increased at the active disease stage of DH. Further analysis of this latter patient subgroup showed that these anti-Hsp autoantibodies decreased in parallel with serum autoantibodies against epidermal and tissue transglutaminase during remission of skin lesions following a gluten-free diet, revealing significantly positive correlations. Although further studies on larger groups of patients will be needed to confirm the present data, our results support the notion that autoantibodies against Hsp60, Hsp70, and Hsp90 deserve attention in the study of the mechanisms that promote the development and maintenance of DH and possibly also the underlying celiac disease as well as potential novel disease biomarkers.

Ureaplasmas: From commensal flora to serious infections

The two existing human pathogen Ureaplasma species containing 14 serovars are associated with a variety of maladies. Colonizing the human urogenital tract, ureaplasmas cause infections mainly in these organs. However, in the special population of immunosuppressed patients or preterm and very low birth weight newborns such serious Ureaplasma infections such as meningitis or pericarditis have been described. Because they lack a cell wall, ureaplasmas are very susceptible to drying and other adverse environmental conditions; therefore, careful attention has to be given to specimen collection and transportation. Commercially available culture based tests made the laboratory diagnosis of Ureaplasma species much easier. PCR methods provide further facilities to get faster diagnosis, simultaneously with serovar identification, quantitation of Ureaplasma or detection of other sexually transmitted infectious pathogens. Although fluoroquinolone, macrolide, and tetracycline resistant strains are known, antibiotic treatment of Ureaplasma infections is not problematic for now. The mechanism of antibiotic resistance has not been entirely understood till now. Biofilm-forming ability of Ureaplasmas can be important in chronic infections and antibiotic resistance. The basic microbiology of Ureaplasma species, such as clinical manifestations, the diagnostic opportunities, and the therapeutic options are reviewed in the current article.

Decreased fibrinolytic potential and morphological changes of fibrin structure in dermatitis herpetiformis

BACKGROUND Recently, high prevalence of cryofibrinogenaemia has been observed in plasma of untreated dermatitis herpetiformis (DH) patients, and the pathological IgA and TG3 deposits in the papillary dermis were found to co-localize with fibrin and fibrinogen. OBJECTIVE To study the fibrinolytic potential in plasma of untreated, dapsone and or/gluten-free diet treated DH patients as well as the in vitro effect of dapsone on the fibrinolytic profile. METHOD Plasma samples of 23 DH patients, 19 healthy subjects and 5 pemphigus vulgaris patients were investigated by a turbidimetric-clot lysis assay. Out of them 5 DH plasma samples representing different fibrinolytic parameters, and 3 healthy controls were selected for parallel fibrin clot preparation. The clot fibrin structure was examined by scanning electron microscopy (SEM), and the diameters of 900 fibrin fibres were determined in each clot. RESULTS A significantly prolonged clot lysis time was detected in untreated DH patients. The turbidity values of DH plasma clots indicated an altered fibrin structure that was also confirmed by SEM: significantly thicker fibrin fibers were observed in untreated, TG3 antibody positive DH patients compared to healthy controls, whereas the fiber diameters of dapsone-treated patients were similar or thinner than the control values. In line with the structural changes of fibrin, the fibrinolytic profile of 5 DH patients under dapsone treatment approached the control values. CONCLUSION This study revealed that the fibrinolytic potential was impaired in the plasma of untreated DH patients, whereas dapsone corrected the fibrinolytic defect. These data suggest a pathogenic role for plasma-derived factors in the development of skin symptoms and add a new aspect to the long-known beneficial, symptomatic effect of dapsone in active DH.

Skin-homing CD8+ T cells preferentially express GPI-anchored peptidase inhibitor 16, an inhibitor of cathepsin K

This study sought to identify novel CD8+ T cell homing markers by studying acute graft versus host disease (aGvHD), typically involving increased T cell homing to the skin and gut. FACS‐sorted skin‐homing (CD8β+/CLA+), gut‐homing (CD8β+/integrinβ7+), and reference (CD8β+/CLA–/integrinβ7–) T cells were compared in patients affected by cutaneous and/or gastrointestinal aGVHD. Microarray analysis, qPCR, and flow cytometry revealed increased expression of peptidase inhibitor 16 (PI16) in skin‐homing CD8+ T cells. Robust association of PI16 with skin homing was confirmed in all types of aGvHD and in healthy controls, too. PI16 was not observed on CLA+ leukocytes other than T cells. Induction of PI16 expression on skin‐homing T cells occurred independently of vitamin D3. Among skin‐homing T cells, PI16 expression was most pronounced in memory‐like CD45RO+/CD127+/CD25+/CD69−/granzyme B− cells. PI16 was confined to the plasma membrane, was GPI‐anchored, and was lost upon restimulation of memory CD8+ T cells. Loss of PI16 occurred by downregulation of PI16 transcription, and not by Phospholipase C (PLC)‐ or Angiotensin‐converting enzyme (ACE)‐mediated shedding, or by protein recycling. Inhibitor screening and pull‐down experiments confirmed that PI16 inhibits cathepsin K, but may not bind to other skin proteases. These data link PI16 to skin‐homing CD8+ T cells, and raise the possibility that PI16 may regulate cutaneous cathepsin K.

Az epidermolysis bullosa szájüregi tünetei és annak ellátása

The aim of this comprehensive article is to provide guidelines for the daily treatment of patients with epidermolysis bullosa, thus contributing to the attainment of their higher quality of life through the improvement of their oral health. Moreover, it is our intention to facilitate the cooperation among Hungarian general practitioners, dermatologists and dentists. Relying on recent research findings of the international literature, we intend to help general practitioners or dermatologists treating epidermolysis bullosa patients on a daily basis by identifying symptoms that require consulting an oral professional on the one hand, and to present the most important prevention strategies and further treatments advised for dentists on the other. Focusing on various aspects of dental treatment, we specify how a dentist can treat the patient without causing additional wounds or pain, and what kinds of therapy are justified by this approach. Orv Hetil. 2017; 158(40): 1577-1583.Absztrakt: Jelen osszefoglalo mű celja, hogy utmutatot adjon az epidermolysis bullosa mindennapi ellatasaban, a betegek oralis egeszsegenek es ezen keresztul eletminőseguk szinvonalanak emeleseben, valamint tamogassa a magyar altalanos orvosok, bőrgyogyaszok es a fogorvosok kozotti kooperaciot. A nemzetkozi irodalom alapjan segitseget szeretnenk nyujtani abban, hogy a beteget gondozo bőrgyogyasz vagy a haziorvos mikor vonjon be szajureggel foglalkozo szakembert, illetve a fogorvosnak, hogy milyen fő prevencios vagy azon tulmutato teendői vannak. A fogorvosi kezeles kulonboző aspektusain keresztul bemutatjuk, hogy egy fogorvos milyen modon lathatja el a pacienseket tovabbi sebek vagy fajdalom okozasa nelkul, valamint milyen beavatkozasokat es hogyan tud szamukra megvalositani. Orv Hetil. 2017; 158(40): 1577–1583.

Tumorőssejtek szerepe a melanoma progressziójában és heterogenitásában

Over the past decade a rare cell population called cancer stem cells has been identified in both solid tumors and hematologic cancers. These cells are reminiscent of somatic and embryonic stem cells and play a critical role in the initiation and progression of malignancies. As all stem cells, they are able to undergo asymmetric cell division and hence renew themselves and create various other progenies with heterogenous phenotypes. A growing body of literature suggested that stem cell subpopulations contribute significantly to the growth and metastatic properties of melanoma. This review gives a comprehensive overview of the current literature on melanoma stem cells, with a special emphasis on the signaling pathways responsible for the homeostatic growth of melanocytes and the uncontrolled proliferation of melanoma cells. The importance of the local microenvironment are demonstrated through summarizing the role of various cell types, soluble factors and cell adhesion molecules in the progression of melanoma and the creation of treatment resistant cancer cell clones. Last but not least, the models of melanoma progression will be introduced and a variety of cellular markers will be presented that may be used to identify and therapeutically target melanoma. Orv. Hetil., 2016, 157(34), 1339-1348.Absztrakt A szolid es hematologiai tumorok legtobbjeben mara olyan sejtpopulaciokat azonositottak, amelyek a daganatok kis szazalekat alkotjak, megis kiemelkedő szerepet toltenek be a daganat terjedesenek előmozditasaban. Ezek az ugynevezett tumorőssejtek a szomatikus es embrionalis őssejtekhez hasonlo viselkedest mutatnak, aszimmetrikus osztodassal onmegujitasra kepesek es heterogen sejtpopulaciokat is letrehoznak. Egyre tobb kutatas alatamasztja, hogy a malignus melanomak progresszioja mogott is tumoros őssejtek allnak. Nem tisztazott kerdes azonban, hogy a tumorigenicitasert vajon kizarolag melanomaőssejtek szubpopulacioi felelősek vagy pluripotens őssejtte barmely melanomasejt dedifferencialodhat. Jelen kozlemeny a pluripotens melanomaőssejtekről kivan atfogo kepet nyujtani, kulonos tekintettel azokra a mechanizmusokra, amelyek a melanocyta-őssejtek differencialodasat szabalyozzak, ugyanakkor a melanomaőssejtekben szabalyozatlanul műkodnek. Bemutatasra kerul a mikrokornyezet sejtjeinek, sejtadhezios m...

Cover Image: Detection of hair follicle-associated Merkel cell polyomavirus in an immunocompromised host with follicular spicules and alopecia.

DEAR EDITOR, A possible contributory role of Merkel cell polyomavirus (MCPyV) in the formation of facial follicular spicules in multiple myeloma is debated. Here we report a case of chronic, widespread follicular papules with spicules and scalp hair loss in an immunocompromised host following double lung transplantation. We demonstrate the presence of MCPyV DNA (small T antigen) and intranuclear large T antigen in CK71 inner root sheath cells of the affected hair follicles. The symptoms resolved completely after initiation of systemic valganciclovir treatment followed by prompt recurrence after stopping therapy. Our findings argue that MCPyV may be an aetiological contributor to non-neoplastic follicular pathology in immunocompromised hosts. This image shows clinical presentation before (a–c) and 5 months after (d–f) initiation of systemic valganciclovir treatment. Immunostaining demonstrates overlap of the large T antigen of MCPyV (red) with the nuclei (blue) of CK71 (green) inner root sheath cells of hair follicles (g). Iterative restoration shows three-dimensional overlap of large T antigen with the nucleus.