Squamous Cell Carcinoma Arising in Discoid Lupus Erythematosus of the Nail Unit.

Introduction: Discoid lupus erythematosus can affect periungual tissues leading to onychodystrophy. Squamous cell carcinoma can occur in persistent scars of discoid lupus; this rare occurrence has not yet been reported on the nail unit. Case presentation: we report a case of squamous cell carcinoma occurring on the distal phalanx of the thumb in a patient with longstanding periungual discoid lupus on several fingernails. Discussion: Periungual discoid lupus erythematosus is rare. The scars caused by this disease can very rarely develop into squamous cell carcinoma. This is the first report of this occurrence at the periungual tissues.

Generation of Cytotoxic T Cells and Dysfunctional CD8 T Cells in Severe COVID-19 Patients.

COVID-19, the infectious disease caused by SARS-CoV-2, has spread on a pandemic scale. The viral infection can evolve asymptomatically or can generate severe symptoms, influenced by the presence of comorbidities. Lymphopenia based on the severity of symptoms in patients affected with COVID-19 is frequent. However, the profiles of CD4+ and CD8+ T cells regarding cytotoxicity and antiviral factor expression have not yet been completely elucidated in acute SARS-CoV-2 infections. The purpose of this study was to evaluate the phenotypic and functional profile of T lymphocytes in patients with moderate and severe/critical COVID-19. During the pandemic period, we analyzed a cohort of 62 confirmed patients with SARS-CoV-2 (22 moderate cases and 40 severe/critical cases). Notwithstanding lymphopenia, we observed an increase in the expression of CD28, a co-stimulator molecule, and activation markers (CD38 and HLA-DR) in T lymphocytes as well as an increase in the frequency of CD4+ T cells, CD8+ T cells, and NK cells that express the immunological checkpoint protein PD-1 in patients with a severe/critical condition compared to healthy controls. Regarding the cytotoxic profile of peripheral blood mononuclear cells, an increase in the response of CD4+ T cells was already observed at the baseline level and scarcely changed upon PMA and Ionomycin stimulation. Meanwhile, CD8+ T lymphocytes decreased the cytotoxic response, evidencing a profile of exhaustion in patients with severe COVID-19. As observed by t-SNE, there were CD4+ T-cytotoxic and CD8+ T with low granzyme production, evidencing their dysfunction in severe/critical conditions. In addition, purified CD8+ T lymphocytes from patients with severe COVID-19 showed increased constitutive expression of differentially expressed genes associated with the caspase pathway, inflammasome, and antiviral factors, and, curiously, had reduced expression of TNF-α. The cytotoxic profile of CD4+ T cells may compensate for the dysfunction/exhaustion of TCD8+ in acute SARS-CoV-2 infection. These findings may provide an understanding of the interplay of cytotoxicity between CD4+ T cells and CD8+ T cells in the severity of acute COVID-19 infection.

Upregulation of PD-1 Expression and High sPD-L1 Levels Associated with COVID-19 Severity.

COVID-19 has several mechanisms that can lead to lymphocyte depletion/exhaustion. The checkpoint inhibitor molecule programmed death protein 1 (PD-1) and its programmed death-ligand 1 (PDL-1) play an important role in inhibiting cellular activity as well as the depletion of these cells. In this study, we evaluated PD-1 expression in TCD4+, TCD8+, and CD19+ lymphocytes from SARS-CoV-2-infected patients. A decreased frequency of total lymphocytes and an increased PD-1 expression in TCD4+ and CD19+ lymphocytes were verified in severe/critical COVID-19 patients. In addition, we found a decreased frequency of total monocytes with an increased PD-1 expression on CD14+ monocytes in severe/critical patients in association with the time of infection. Moreover, we observed an increase in sPD-L1 circulant levels associated with the severity of the disease. Overall, these data indicate an important role of the PD-1/PDL-1 axis in COVID-19 and may provide a severity-associated biomarker and therapeutic target during SARS-CoV-2 infection.

Pseudomonas aeruginosa as an uncommon agent of infectious panniculitis.

Pseudomonas aeruginosa is a Gram-negative bacillus that frequently causes septicemia, abscesses and infections in skin wounds. Panniculitis caused by this microorganism is unusual and there are few well-documented cases, none of them in a patient with systemic lupus erythematosus. The present report describes an immunosuppressed patient with systemic lupus erythematosus who developed panniculitis caused by Pseudomonas aeruginosa, with a review of the literature on this rare presentation.

Pseudomonas aeruginosa as an uncommon agent of infectious panniculitis

Abstract Pseudomonas aeruginosa is a Gram-negative bacillus that frequently causes septicemia, abscesses and infections in skin wounds. Panniculitis caused by this microorganism is unusual and there are few well-documented cases, none of them in a patient with systemic lupus erythematosus. The present report describes an immunosuppressed patient with systemic lupus erythematosus who developed panniculitis caused by Pseudomonas aeruginosa, with a review of the literature on this rare presentation.

Porokeratosis of the Nail Unit: Case Series and Review.

BACKGROUND: The lesions of porokeratosis (PK) lead to skin atrophy and scarring as long as they spread centrifugally. PK affecting the nail unit is seldom described. OBJECTIVE: The aim was to revise the previously reported cases of ungual PK and to present 3 new cases. METHODS: A PubMed search was performed with the keywords "nail" and "porokeratosis." Previously reported cases as well as 3 new cases are depicted in tables. RESULTS: Only 11 cases of ungual PK were found; 3 new cases have been added. All patients presented with typical lesions of PK (Mibelli, isolated, segmental, or ostial eccrine types) that happened to affect nails due to nail matrix or nail bed compromise, resulting in mild to severe nail scarring, including irreversible anonychia. The present 3 case series contrast with the previous single case reports. CONCLUSIONS: PK affecting the nails is exceedingly rare. Changes in nails affected by PK are irreversible, since, as on the skin, this is a chronic scarring process.

Impact of Inflammatory Immune Dysfunction in Psoriasis Patients at Risk for COVID-19.

Psoriasis is an immune-mediated dermatosis usually associated with comorbidities. Treatment varies from topicals to systemic drugs and data on susceptibility to viral infections in psoriatic patients are scarce. The objectives of this study were to analyze psoriatic patients on different therapies who were at risk for COVID-19 for seroprevalence of SARS-COV-2, pro-inflammatory cytokine profile, comorbidities and outcomes in order to unveil the immunological mechanisms involved in the anti-viral response in patients with psoriasis. Seventy-five patients with psoriasis were divided according to treatment: immunobiologics, methotrexate, topicals and acitretin. Twenty healthy controls were included. Plasma samples were collected for: IgG SARS-COV-2 (ELISA); IL-27, IL-29 and IL-18 (ELISA); and IL-1ß, IL-17A, IL-6 and TNF (cytometric array). Seropositivity for SARS-COV-2 was detected in 24 out of 75 psoriasis patients and did not relate to COVID-19 symptoms and/or hospitalization, despite associated comorbidities. Psoriasis patients who were asymptomatic for SARS-COV-2 exhibited immune imbalance with high levels of IL-18, IL-17A and IL-6, and low levels of IL-27 compared to healthy controls. Psoriasis groups showed significant increased cytokine levels only in the group with immunobiologics. Despite immune deviations and lower IL-27, which has a potential antiviral impact, psoriatic patients did not exhibit complications related to COVID-19. An understanding of this kind of proinflammatory profile of psoriatic patients and of the lack of severe outcomes for COVID-19 is essential to establish novel therapeutic approaches and preventive measures, including with regard to the concomitance of viral infections.

SARS-CoV-2 Infection and CMV Dissemination in Transplant Recipients as a Treatment for Chagas Cardiomyopathy: A Case Report.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has infected over 90 million people worldwide, therefore it is considered a pandemic. SARS-CoV-2 infection can lead to severe pneumonia, acute respiratory distress syndrome (ARDS), septic shock, and/or organ failure. Individuals receiving a heart transplantation (HT) may be at higher risk of adverse outcomes attributable to COVID-19 due to immunosuppressives, as well as concomitant infections that may also influence the prognoses. Herein, we describe the first report of two cases of HT recipients with concomitant infections by SARS-CoV-2, Trypanosoma cruzi, and cytomegalovirus (CMV) dissemination, from the first day of hospitalization due to COVID-19 in the intensive care unit (ICU) until the death of the patients.

Case Report: COVID-19 and Chagas Disease in Two Coinfected Patients.

American trypanosomiasis, also named Chagas disease (CD), is an anthropozoonosis caused by the protozoan parasite Trypanosoma cruzi. The disease affects millions of people worldwide, leading yearly to approximately 50,000 deaths. COVID-19, generated by SARS-CoV-2, can lead to lymphopenia and death. We hereby describe the first report of two patients with CD and COVID-19 coinfection, from hospitalization until patients' death.

Anatomical Basis of the Myofascial Trigger Points of the Gluteus Maximus Muscle.

Myofascial pain syndrome is characterized by pain and limited range of motion in joints and caused by muscular contracture related to dysfunctional motor end plates and myofascial trigger points (MTrPs). We aimed to observe the anatomical correlation between the clinically described MTrPs and the entry point of the branches of the inferior gluteal nerve into the gluteus maximus muscle. We dissected twenty gluteus maximus muscles from 10 human adult cadavers (5 males and 5 females). We measured the muscles and compiled the distribution of the nerve branches into each of the quadrants of the muscle. Statistical analysis was performed by using Student's t-test and Kruskal-Wallis tests. Although no difference was observed either for muscle measurements or for distribution of nerve branching among the subjects, the topography of MTrPs matched the anatomical location of the entry points into the muscle. Thus, anatomical substract of the MTrPs may be useful for a better understanding of the physiopathology of these disorders and provide basis for their surgical and clinical treatment.

Adjuvant effect of killed Propionibacterium acnes on mouse peritoneal B-1 lymphocytes and their early phagocyte differentiation.

B-1 lymphocytes are the predominant cells in mouse peritoneal cavity. They express macrophage and lymphocyte markers and are divided into B-1a, B-1b and B-1c subtypes. The role of B-1 cells is not completely clear, but they are responsible for natural IgM production and seem to play a regulatory role. An enriched B-1b cell population can be obtained from non-adherent peritoneal cell cultures, and we have previously demonstrated that these cells undergo differentiation to acquire a mononuclear phagocyte phenotype upon attachment to the substrate in vitro. Nevertheless, the B-1 cell response to antigens or adjuvants has been poorly investigated. Because killed Propionibacterium acnes exhibits immunomodulatory effects on both macrophages and B-2 lymphocytes, we analyzed whether a killed bacterial suspension or its soluble polysaccharide (PS) could modulate the absolute number of peritoneal B-1 cells in BALB/c mice, the activation status of these cells and their ability to differentiate into phagocytes in vitro. In vivo, P. acnes treatment elevated the absolute number of all B-1 subsets, whereas PS only increased B-1c. Moreover, the bacterium increased the number of B-1b cells that were positive for MHC II, TLR2, TLR4, TLR9, IL-4, IL-5 and IL-12, in addition to up-regulating TLR9, CD80 and CD86 expression. PS increased B-1b cell expression of TLR4, TLR9, CD40 and CD86, as well as IL-10 and IL-12 synthesis. Both of the treatments decreased the absolute number of B-1b cells in vitro, suggesting their early differentiation into B-1 cell-derived phagocytes (B-1CDP). We also observed a higher phagocytic activity from the phagocytes that were derived from B-1b cells after P. acnes and PS treatment. The adjuvant effect that P. acnes has on B-1 cells, mainly the B-1b subtype, reinforces the importance of B-1 cells in the innate and adaptive immune responses.

Modulation of the type I hypersensitivity late phase reaction to OVA by Propionibacterium acnes-soluble polysaccharide.

Late phase reaction (LPR) of immediate hypersensitivity is a Th2 response characterized by eosinophil recruitment and related to allergic asthma pathogenesis. Several strategies were developed trying to control the tissue damage observed in this reaction. Recently, we verified that killed Propionibacterium acnes (P. acnes), a Gram-positive bacillus, immunomodulated LPR in a murine model, potentiating or suppressing it depending on the treatment protocol used. However, the bacterium compounds responsible for this effect are not known, leading us to investigate if P. acnes purified soluble polysaccharide (PS) could be a major component involved on the modulation induced by the bacterium. Recently, we demonstrated that PS, like P. acnes, induces adjuvant effect on DNA vaccine, increases bone marrow dendritic cell precursors in vivo and its maturation in vitro, and modulates in vitro macrophage tumoricidal activity. Herein, we determined the chemical PS composition, which is mainly constituted by galactopyranose, ribopyranose, arabinopyranose, glucopyranose, ribofuranose and mannopyranose, and analyzed its capacity to modulate the immediate hypersensitivity in mice. Animals were subcutaneously implanted with coagulated hen's egg white (HEW) and 14 days later challenged with ovalbumin (OVA) in the footpad, developing a typical LPR after 24h. Similarly to the whole bacterium, Th2 response to OVA was potentiated when PS was administered concomitantly to HEW implantation, by increase in footpad eosinophilia and IL-4-producing spleen cells, and decrease in anti-OVA IgG2a titers and IL-12- or IFN-gamma-producing cells. On the other hand, the reaction was abrogated when HEW implantation was performed 1 week after PS-treatment, by decrease in footpad swelling, eosinophilia and anti-OVA IgG1 levels, and increase in IgG2a titers and IL-12-producing cells. These data suggest that PS seems to be the major P. acnes compound responsible for its effects on the modulation of immediate hypersensitivity reaction in mice.