Defects In Cell-mediated Immunity Research Articles

A case of severe folliculitis decalvans

Folliculitis decalvans is a difficult to treat rare neutrophilic dermatosis that affects the scalp and leads to permanent scarring. The pathogenesis is currently not well understood; the influence of S.aureus antigens, a disorder of the skin microbiome, a defect in cell-mediated immunity, and an imbalance of pro-inflammatory cytokines are assumed. This disease is often associated with a marked decrease in quality of life, because in addition to significant external manifestations, the patient may experience pain, itching and burning in the areas of the rash. The main problem is that there is currently no effective therapy for this disease. Treatment options include systemic antibiotics, topical and intralesional corticosteroids, dapsone, isotretinoin, biologics, and photodynamic therapy. We present a brief overview of the main methods of therapy and a clinical case of a long course of severe folliculitis decalvans, refractory to the main methods of treatment.

HIV infection in the practice of a family doctor and the possibility of AIDS therapy

AIDS, or acquired immunodeficiency syndrome, was originally defined by the Centers for Disease Control as "the presence of a reliably diagnosable disease in which there is at least a mild defect in cell-mediated immunity". The modern definition includes the presence of a group of various disorders caused by opportunistic flora, diagnosed presumably or definitively in individuals with laboratory-proven HIV infection in the absence of other reliable causes of immunodeficiency. From a practical standpoint, the clinician should consider HIV infection as a spectrum of disorders ranging from primary infection, with or without acute HIV syndrome, and asymptomatic infection to overt disease. This article is devoted to the issues of classification, clinical symptoms, and approaches to the diagnosis and treatment of secondary immunodeficiency disorders on the example of AIDS caused by the human immunodeficiency virus (HIV).

Cryptococcal Meningoencephalitis and Immune Reconstitution Inflammatory Syndrome in a patient on Tocilizumab Therapy: A Case Report (P1-10.005)

<h3>Objective:</h3> To describe a case of cryptococcal meningoencephalitis complicated by immune reconstitution inflammatory syndrome (IRIS), vasculitis, ischemic strokes, and hydrocephalus. <h3>Background:</h3> Cryptococcus neoformans is the most common cause of fungal meningitis worldwide and typically affects individuals with defects in cell-mediated immunity. A 71-year-old female with giant cell arteritis on daily prednisone and monthly Tocilizumab infusions presented with worsening headaches for 2 weeks and new-onset confusion for 3 days. Initial workup revealed hyponatremia (sodium 125 mmol/L) and community acquired pneumonia. She was treated with antibiotics, but her mental status rapidly declined necessitating endotracheal intubation. MRI Brain demonstrated multifocal areas of diffusion restriction in the bilateral cerebral and cerebellar hemispheres, basal ganglia, and brainstem with diffuse leptomeningeal enhancement. Cerebrospinal fluid (CSF) studies revealed an elevated opening pressure of 28 cm H₂O, positive CSF cryptococcal antigen, and CSF fungal cultures grew cryptococcus neoformans. She was started on empiric liposomal amphotericin B and flucytosine before the cryptococcal antigen and cultures resulted. Despite treatment, her neurological status continued to decline with repeat MRI showing new ischemic infarctions, subarachnoid hemorrhages, and leptomeningeal and parenchymal enhancement. Digital subtraction angiography revealed cerebral vasospasm and possible vasculitis. Repeat lumbar puncture demonstrated persistently elevated opening pressure, continued pleocytosis, and increased protein. She was continued on antifungal therapy and received IV methylprednisolone for IRIS. She additionally underwent ventriculoperitoneal (VP) shunt placement. Despite these interventions, her clinical status continued to deteriorate and she was palliatively extubated. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> N/A <h3>Conclusions:</h3> This patient presented with cryptococcal meningoencephalitis in the setting of immune suppression from prednisone and tocilizumab, a monoclonal antibody that targets the IL-6 receptor. Despite early and appropriate treatment, she continued to worsen with multiple complications including IRIS, a dysfunctional inflammatory response to infection precipitated by immune recovery. In patients treated appropriately for cryptococcal meningoencephalitis, a failure to respond should raise concern for complicating conditions. <b>Disclosure:</b> Dr. Navalkar has nothing to disclose. Dr. Sui has nothing to disclose. The institution of Dr. Bashir has received research support from NIH. The institution of Dr. Bashir has received research support from PICORI. The institution of Dr. Bashir has received research support from Sanofi. Dr. Bashir has received research support from GWSP. The institution of Dr. Bashir has received research support from Roche. The institution of Dr. Bashir has received research support from Novartis. The institution of Dr. Bashir has received research support from Hoffmann-La Roche.

Comparative study on the effectiveness of intralesional Measles, Mumps, and Rubella vaccine and intralesional vitamin D3 injection in the treatment of verruca

Background: Human papillomavirus (HPV) is the causative agent of verruca and is contagious, recurrent, and recalcitrant due to defects in cell-mediated immunity. No single mode of treatment is completely effective. The most commonly used treatment options are destructive and lead to scarring. The emerging new modality of treatment is immunotherapy, which acts by enhancing cell-mediated immunity (CMI) against HPV to clear treated as well as remote warts. Objectives: The objective was to compare the efficacy of intralesional Measles, Mumps, and Rubella (MMR) vaccine and intralesional vitamin D3 in cutaneous warts. Materials and Methods: A randomized, hospital-based, single-blind study on forty patients divided into two groups (groups A and B), comprising twenty patients each, was conducted. In group A, intralesional MMR vaccine 0.5 mL was injected into the base of warts. In group B, intralesional vitamin D3 0.5 mL was injected into the base of warts after achieving local anesthesia. Sessions were performed in two-week intervals for a maximum number of five sessions. The patients were followed for sixteen weeks. Results: In group A (MMR vaccine), a complete response was seen in 75% (15/20) of the patients, a moderate response in 15% (3/20), a partial response in 5% (1/20), and no response in 5% (1/20). In group B (vitamin D3), a complete response was seen in 65% (13/20) of the patients, a moderate response in 15% (3/20), a partial response in 10% (2/20), and no response in 10% (2/20). No recurrence was noticed after follow-up in either of the two groups. Conclusion: Immunotherapy is an option that is easy, safe, cost-effective, and well-tolerated with minimal side effects. Key words: Verruca; Intralesional MMR; Intralesional vitamin D3; Immunotherapy

Septic arthritis by Nocardia farcinica: Case report and literature review

Nocardiosis is a bacterial infection caused by organisms of the Nocardia genus. The disease typically involves the skin, central nervous system or pulmonary system. Very rarely nocardiosis can cause disease of other organs including bone and joints. Nocardiosis is typically a chronic, somewhat indolent infection, occurring in patients with defective cell mediated immunity. We describe a 78-year-old female with right shoulder septic arthritis resulting from Nocardia farcinica with associated involvement of her skin and lungs as well. She was treated with surgical debridement and combination antibiotic therapy. We also share a literature review of bone and joint infection caused by the N. farcinica species, highlighting its rarity. Understanding uncommon manifestations of nocardiosis allows for early recognition and treatment of the condition and optimal patient care.

Cryptococcal Meningoencephalitis in an Immunosuppressed Patient with Chronic Lymphocytic Leukemia

Cryptococcal meningoencephalitis, an invasive fungal infection caused by an encapsulated fungus Cryptococcus neoformans should be suspected in immune compromised individuals with defective cell-mediated immunity and patients on immunosuppressive drugs with recent development of fever, confusion and loss of consciousness. A rapid diagnosis is fundamental for decreasing morbidity and mortality from cryptococcal disease. Cerebrospinal fluid (CSF) study and simple stain like India Ink Stain can be performed for diagnosis of cryptococcal meningoencephalitis. Here, we report a case of cryptococcal meningoencephalitis in chronic lymphocytic leukemia (CLL) patient on immunosuppressive drugs diagnosed by CSF study and India ink stain which responded dramatically with antifungal agents after diagnosis. JAFMC Bangladesh. Vol 16, No 2 (December) 2020: 87-89

Non-tuberculous mycobacteria infections in peritoneal dialysis: Lessons from a 16-year single-centre experience

Dear Editor, Non-tuberculous mycobacteria (NTM) infections in peritoneal dialysis (PD) patients are uncommon, but they have been increasingly recognised as causes of morbidity. NTM are generally non-pathogenic, but given their abundance in the environment, they pose a threat to PD patients who have broken integument, indwelling devices and relative defects in cell-mediated immunity.1 The growth

Enhanced Spontaneous Anti-Tumor Cytotoxicity of Natural Killer Cells in Cutaneous T-Cell Lymphoma Patients

Cutaneous T-cell lymphoma (CTCL) is characterized by the expansion of malignant CD4+ T cells in the skin. There are two main subtypes of CTCL, mycosis fungoides (MF) and Sézary syndrome (SS). Previous studies have demonstrated defects in cell-mediated immunity, including altered cytokine profiles and decreased neutrophil function, and patients often have recurring bacterial and viral infections. Recent studies have shown increased expression of interleukin (IL)-15 in malignant CD4+ T cells in CTCL patients (Mishra et al., Cancer Discovery, 2016). Since IL-15 can enhance NK cell differentiation and activation, we hypothesized that NK cells from CTCL patients might have phenotypic and functional alterations due to these changes in homeostatic IL-15 levels.To evaluate the absolute number of NK cells in CTCL patients, CD56+Lineage- lymphocytes were quantitated by flow cytometry. SS patients had significantly fewer NK cells as compared to normal donors (mean ± SEM of absolute cell numbers in normal donors=0.2442 ± 0.02, n=51; SS=0.1072 ± 0.02, n=9; MF=0.2161 ± 0.01, n=112; unpaired t-test normal vs. SS, p=0.007). NK cell counts were significantly associated with overall survival, with the short-term risk of death increasing by 87.5% for every increase in 0.1 of absolute NK cell counts on univariate analysis utilizing the Cox proportional hazards model (Figure 1A; p=0.0413). We then examined the cytotoxic capacity of NK cells (CD56+Lineage-) freshly purified from both MF and SS patients by standard chromium release assay. There was a significantly higher level of specific lysis of tumor cells (K562 target cells) by NK cells from CTCL patients as compared to normal donors (Figure 1B, at 50:1 ratio mean ± SEM of percent NK cell cytotoxicity in normal vs CTCL = 27.47 ± 4.76, n=13 vs. 52.54 ± 4.88, n=12, unpaired t-test, p=0.001). Upon further transcript analysis of NK cell cytolytic mediators from CTCL patients compared to normal donors, we observed significantly increased levels of perforin (mean ± SEM of relative RNA in normal vs CTCL = 91.39 ± 9.18, n=3 vs. 485.7 ± 43.15, n=7, unpaired t-test, p=0.0004) and granzyme B (143 ± 23.79, n=3 vs. 431 ± 68.13, n=7 unpaired t-test, p=0.03). In addition, we observed increased levels of interferon-gamma and Fas Ligand (5.149 ± 0.4775, n=3 vs.13.93 ± 1.52, n=7; unpaired t-test p=0.007), indicating NK cells from CTCL patients exhibited consistently elevated activation patterns as compared to normal donor NK cells. We then examined the expression pattern of the IL-15 receptor complex on NK cells in CTCL patients as compared to normal donors by RNA sequencing. There was a significant elevation in IL-15Rα (mean ± SEM of relative RNA in normal vs CTCL = 0.8677 ± 0.1018, n=3 vs. 1.772 ± 0.2055, n=7; p=0.03) and IL-15Rγ (57.02 ± 7.525, n=3 vs. 154.7 ± 12.14, n=7; p=0.001), while IL-15Rβ was also elevated (128 ± 23.68, n=3 vs. 223.2 ± 25.43, n=7; p=0.056). Next we evaluated protein levels of phosphorylated signal transducer and activator of transcription 5 (p-STAT5) in fresh whole blood as the surrogate marker of IL-15 signaling. Preliminary findings demonstrate an increase in p-STAT5 in CTCL patients as compared to normal donors (mean ± SEM of fluorescent intensity in normal donors vs CTCL patients =1506 ± 90.82, n=5 vs. 1270 ± 50.59, n=4; unpaired t-test; p=0.07).These data suggest that NK cell activation is enhanced in patients with CTCL, including MF patients with disease localized to the skin. Further investigations aimed at understanding the disconnect between NK cell numbers, activation, and disease control in CTCL patients are warranted. [Display omitted] DisclosuresPorcu:Kiowa: Research Funding; Miragen: Research Funding; Celgene: Research Funding; Tetralogic: Research Funding; Innate Pharma: Research Funding; Kura: Research Funding; Galderma: Research Funding; Cell Medica: Research Funding. William:Miragen: Consultancy, Honoraria.

Clinicopathologic features of Good’s syndrome: Two cases and literature review

BackgroundGood’s syndrome (GS) is an immunodeficiency disease, causing thymoma, low or absent B-cells, hypogammaglobulinemia, and defects in cell-mediated immunity. The most common clinical presentation is recurrent infection, followed by refractory diarrhea, due to the immunodeficiency. However, there are only few reports on intestinal endoscopy and pathology.Case summaryWe report here two typical GS cases with diarrhea as the prominent manifestation. Both cases presented with thymoma combined with immunodeficiency, characterized by hypogammaglobulinemia, low or absent B lymphocytes, and decreased T-cells with inverted CD4+/CD8+ T-cell ratio, while two GS patients were evaluated by endoscopy revealed mucosal edema and fine-granular or nodular appearance changes in the small intestine. Histological examination showed chronic inflammation and villous atrophy. A very interesting finding is that the inflammatory cell infiltration in the two GS cases was different. In one case, predominantly CD138+ plasma cells with only scattered CD3+ T-cells infiltration were revealed, while in another, it showed predominantly T-cells infiltration without plasma cells in the lamina propria. Although GS cases shared various clinical characteristics with common variable immunodeficiency (CVID) cases, they still differed from CVID cases in terms of its late onset, lack of familial clusters, low or absent peripheral blood B lymphocytes, absence of lymphoid hyperplasia, and plasma cells infiltration in the lamina propria in some patients. Although both patients had been diagnosed previously with recurrent diarrhea, respiratory infection, and thymoma, the association between these conditions and the possibility of GS was not recognized. The patients had remained misdiagnosed for 2 and 4 years, respectively, even after receiving the diagnosis of thymoma. The rarity of GS was likely the primary cause for the lack of disease recognition. Reporting of these cases will help to alert clinicians and raise awareness of this disease.ConclusionGS should be considered among the differential diagnoses for patients with unexplained recurrent diarrhea and opportunistic infection. Although it was regarded as a subset of CVID with thymoma, GS had a different clinical-pathological feature from CVID.

A Study of Awareness and Knowledge about Epidermodysplasia Verruciformis-A Genetic Disorder

Tree man syndrome is a rare inherited skin disorder, including persistent infection caused by human papillomavirus, as a result of which a defect in cell-mediated immunity takes place. This infection results in the growth of scaly macules and papules, mostly on the feet and hands. It is a lifelong disorder that can be treated in surgical and nonsurgical ways. A questionnaire or awareness-based study was conducted among the population of Karachi, Pakistan (both medical and non-medical). It was attended by 506 individuals. To raise the consciousness of this illness. The questions evaluated their knowledge of tree man illness, the possible consequences of the condition and the latest therapies. More than 80% of people were totally unaware of tree man disorder. Only 10% of people were aware or just heard about this disease. The awareness of Tree man syndrome was very low among the people. Steps should be taken to increase awareness about this rare but life-threatening disease.

Disseminated Deep Dermal Trichophyton Rubrum Infection in a Heart Transplant Recipient

<h3>Introduction</h3> The dermatophyte Trichophyton rubrum (T. rubrum) is one of the most common causes of superficial cutaneous mycoses. Although these are often seen in immunosuppressed heart transplant recipients, reports of deep dermatophytoses are rare. Accounts of extensive T. rubrum are even scarcer. We report a case of disseminated deep T. rubrum infection in a heart transplant patient, successfully treated with itraconazole. <h3>Case Report</h3> A 62 year-old systemically well male one year post-cardiac transplantation presented with a 4-month history of painless discharging erythematous nodules. These ranged from 1 to 6 cm in diameter on his upper limbs, lower abdomen, perineum and upper thighs. Histology from skin biopsy showed deep dermal granulomatous inflammation with filamentous fungal hyphae. Mycological studies isolated T. rubrum. This was treated with oral itraconazole and careful dose reduction of tacrolimus. After one month, the patient described a reduction in size of nodules and absence of new lesions. Following three months of itraconazole, the patient achieved a near complete response. The infection remained adequately controlled two months after itraconazole cessation. <h3>Summary</h3> There have been 5 published reports of deep T. rubrum infection over the last 10 years in PubMed, MEDLINE and EMBASE¹. A condition distinct from superficial dermatophytosis, deep dermatophytosis occurs in immunosuppressed individuals with defective cell-mediated immunity². Cases in solid-organ transplant recipients have been described predominantly in kidney recipients³. Disseminated infection has been reported in various bodily sites with the presentation of papulo-nodular lesions⁴ alongside invasive and extensive forms³. Careful monitoring of immunosuppressant level is required to prevent complications when itraconazole (an enzyme inhibitor) is added⁵. Deep dermatophytosis such as T. rubrum should be included in the differential diagnosis of erythematous skin nodules in immunosuppressed patients.

Clinical characteristics and risk factors of Talaromyces marneffei infection in human immunodeficiency virus-negative patients: A retrospective observational study.

To investigate the clinical characteristics and risk factors of human immunodeficiency virus (HIV)-negative patients with Talaromyces marneffei (T. marneffei) infection. We retrospectively collected the clinical information of HIV-negative patients with T. marneffei infection from January 1, 2010 to June 30, 2019, and analyzed the related risk factors of poor prognosis. Twenty-five cases aging 22 to 79 years were included. Manifestations of T. marneffei infection included fever, cough, dyspnea, chest pain or distress, lymphadenopathy, ear, nose, and throat (ENT) and/or skin lesions, bone or joint pain, edema and pain in the lower extremities, digestive symptoms, icterus, malaise, and hoarseness. Two cases had no comorbidity, while 23 cases suffered from autoimmune disease, pulmonary disease, cancer, and other chronic diseases. Sixteen cases had a medication history of glucocorticoids, chemotherapy or immunosuppressors. Pulmonary lesions included interstitial infiltration, nodules, atelectasis, cavitary lesions, pleural effusion or hydropneumothorax, bronchiectasis, pulmonary fibrosis, pulmonary edema, and consolidation. The incidence of osteolytic lesions was 20%. Eight patients received antifungal monotherapy, and 11 patients received combined antifungal agents. Fifteen patients survived and ten patients were dead. The Cox regression analysis showed that reduced eosinophil counts, higher levels of blood urea nitrogen (BUN), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactic dehydrogenase (LDH), myoglobin (Mb), procalcitonin (PCT), and galactomannan were related to poor prognosis (hazard ratio [HR]>1, P<0.05). Bone destruction is common in HIV-negative patients with T. marneffei infection. Defective cell-mediated immunity, active infection, multiple system, and organ damage can be the risk factors of poor prognosis.

Septic Pulmonary Embolism in a Patient with Generalized Salmonellosis: a Clinical Case and Meta-Analysis

Nontyphoid Salmonella are gram-negative bacteria that induce Th1-mediated immunity. They rarely lead to a generalized infection, primarily developing in immunocompromised patients with cellular immunity defects. Septic pulmonary embolism is also a rare condition in which emboli contain microorganisms from extrapulmonary infective foci. The article presents a rare clinical case of a patient with pulmonary embolism and generalized nontyphoid salmonellosis due to the presence of Asp299Gly and Thr399Ile genetic polymorphisms in the TLR4 gene. Such a defect of cell-mediated immunity was a trigger for destructive changes in the lung parenchyma, prothrombotic state, and generalization of the infectious process.

Retro-orbital nocardiosis masquerading as a neoplasm- A case report

Nocardiosis caused by an aerobic gram positive, weakly acid fast actinomycete is a localized or disseminated infection. The disease usually affects patients with defective cell mediated immunity. These infections are infrequent but pose a great challenge in terms of diagnosis and treatment as the treatment is prolonged and relapse is known to occur. The incidence has been increasing recently which can be attributed to the improvements in diagnostic facilities and increased prevalence of patients with HIV, chronic alcoholism, diabetes mellitus, patients receiving aggressive antineoplastic chemotherapy, long standing corticosteroid therapy and patients undergoing organ transplantation with immunomodulator drugs. Nocardiosis has been described in patients with underlying chronic pulmonary diseases. Primary nocardial infection includes pulmonary (60-70%), brain, musculoskeletal system and cutaneous or subcutaneous lesions. Disseminated disease is defined by the nocardial involvement in two or more organs. Nocardiosis associated with HIV usually appears in patients with advanced disease with CD4 counts less than 50 cells/mm3. Sulfonamides like trimethoprim-sulfamethoxazole are the drugs of choice for nocardiosis and are successfully used for treatment. Nocardiosis has been described to mimic tuberculosis, aspergillosis, bronchogenic and metastatic lung carcinomas, brain and musculoskeletal tumours. Here we describe an unusual presentation of retro-orbital nocardiosis masquerading as a neoplasm which was successfully treated with cotrimoxazole and ceftriaxone. Keywords: Nocardiosis, Actinomycete, Antineoplastic drugs, HIV, Cotrimoxazole.

Invasive Nocardiosis: Disease Presentation, Diagnosis and Treatment - Old Questions, New Answers?

Nocardia spp. is an environmental filamentous Gram-positive bacterium that may cause infections in humans and, despite recent progress, many challenges remain regarding the management of nocardiosis. This review aims at describing most recently published data regarding the diagnosis, treatment and follow-up of patients with invasive nocardiosis. As nocardiosis mainly affects patients with cell-mediated immunity defects, a comprehensive workup is mandatory in case of invasive nocardiosis occurring in ”apparently healthy patients”. Indeed, invasive nocardiosis might reveal an unknown primary immunodeficiency or the presence of anti-GM-CSF autoantibodies. Even if the diagnosis of nocardiosis mostly relies on direct examination and bacterial culture, a genus-specific PCR may be used for the detection of Nocardia, when directly performed on a clinical sample. Brain imaging should always be performed, even in the absence of neurological symptoms. Cotrimoxazole (trimethoprim/sulfamethoxazole), linezolid, parenteral cephalosporins, carbapenems and amikacin may be used as initial antibiotics to treat nocardiosis. Cotrimoxazole or linezolid can be used as monotherapy in selected patients without brain involvement. Although treatment duration has historically been set to at least 6 months in the absence of central nervous system involvement, shorter durations (<120 days) seem to be associated with a favourable outcome.

Susceptibility of the obese population to COVID-19

•Obesity is a risk factor for disease severity in individuals with coronavirus disease (COVID-19). However, the increased susceptibility of this population to COVID-19 is unclear. We outline several underlying mechanisms that may explain the relationship between obesity and COVID-19 severity. Obesity has an adverse effect on respiratory physiology because increased intra-abdominal adipose tissue can interfere with lung expansion, resulting in reduced lung compliance. Further, fat accumulation in the soft tissue of the pharynx can increase inspiratory resistance, and obesity may be associated with sleep apnea. Obesity is associated with several defects in cell-mediated immunity, including increased levels of pro-inflammatory cytokines. Impaired adipocyte-mediated immune function results in chronically high leptin levels, low adiponectin levels, and anti-inflammatory adipokines. Reduced physical activity can impair several steps of the immune response to viruses. Obesity also promotes a hypercoagulable state, leading to severe consequences. These factors may synergistically play a role in promoting the severity of the disease in obese individuals. A better understanding of the mechanisms by which obesity contributes to the severity of COVID-19 is important for developing more effective treatments.

Immune Complex-Driven Generation of Human Macrophages with Anti-Inflammatory and Growth-Promoting Activity.

To maintain homeostasis, macrophages must be capable of assuming either an inflammatory or an anti-inflammatory phenotype. To better understand the latter, we stimulated human macrophages in vitro with TLR ligands in the presence of high-density immune complexes (IC). This combination of stimuli resulted in a broad suppression of inflammatory mediators and an upregulation of molecules involved in tissue remodeling and angiogenesis. Transcriptomic analysis of TLR stimulation in the presence of IC predicted the downstream activation of AKT and the inhibition of GSK3. Consequently, we pretreated LPS-stimulated human macrophages with small molecule inhibitors of GSK3 to partially phenocopy the regulatory effects of stimulation in the presence of IC. The upregulation of DC-STAMP and matrix metalloproteases was observed on these cells and may represent potential biomarkers for this regulatory activation state. To demonstrate the presence of these anti-inflammatory, growth-promoting macrophages in a human infectious disease, biopsies from patients with leprosy (Hanseniasis) were analyzed. The lepromatous form of this disease is characterized by hypergammaglobulinemia and defective cell-mediated immunity. Lesions in lepromatous leprosy contained macrophages with a regulatory phenotype expressing higher levels of DC-STAMP and lower levels of IL-12, relative to macrophages in tuberculoid leprosy lesions. Therefore, we propose that increased signaling by FcγR cross-linking on TLR-stimulated macrophages can paradoxically promote the resolution of inflammation and initiate processes critical to tissue growth and repair. It can also contribute to infectious disease progression.

The impact of diabetes on COVID‐19 infection

The impact of diabetes on <scp>COVID</scp>‐19 infection

CAVITARY LUNG LESION AFTER RENAL TRANSPLANT

SESSION TITLE: Monday Fellow Case Report Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: Opportunistic infections are serious complications that can occur after renal transplant. While potent immunosuppressive therapy has improved graft survival after transplantation, susceptibility to infections remains a significant concern – particularly pulmonary infections. CASE PRESENTATION: A 54-year-old female with a history of lupus nephritis status-post deceased donor kidney transplant 9 months prior presented to clinic with two weeks of fevers, nonproductive cough, and tender subcutaneous nodules on her breast and thigh. Her post-transplant course had been complicated by CMV viremia. She was undergoing evaluation for declining renal function, concerning for graft rejection, and had required adjustment of her tacrolimus for supratherapeutic levels. On evaluation, her chest x-ray showed a right apical infiltrate, and she was admitted to the hospital when chest computed tomography demonstrated a right upper lobe cavitary lesion. She underwent bronchoscopy with bronchoalveolar lavage (BAL) of the right upper lobe and biopsy of her thigh subcutaneous nodule. Within 72 hours, the BAL fluid and wound culture grew Nocardia farcinica, suggesting disseminated Nocardia infection. Magnetic resonance imaging of the brain was performed, which showed no evidence of central nervous system (CNS) involvement. She was treated with intravenous trimethoprim/sulfamethoxazole and imipenem-cilastin. DISCUSSION: Nocardia is a Gram-positive filamentous bacterium that primarily affects hosts with defects in cell-mediated immunity. The incidence of nocardiosis in solid organ transplant recipients varies from 0.7% to 3.5%. Significant risk factors include high-dose corticosteroids, CMV disease in the preceding 6 months, and high levels of calcineurin inhibitors in the preceding 30 days. Pulmonary nocardiosis infection typically occurs from inhalation of contaminated particles in soil, decaying vegetation, or water. Cavitation within the pulmonary nodules occurs in approximately 1/3 of cases. Disseminated disease occurs in about 30% of patients, with the most frequent extra-pulmonary sites being the subcutaneous tissues and the brain. Biopsy of subcutaneous lesions yields a diagnosis in approximately 24% of patients, and BAL in 20%. Initial treatment should include two agents effective against Nocardia and have the ability to penetrate the CNS. Duration of treatment is a minimum of 6 months, and at least 12 months if there is CNS involvement. CONCLUSIONS: Nocardia is a rare opportunistic infection that most frequently occurs in the first 12 months post-transplant. It is a severe disease that confers a mortality rate of approximately 20% in solid organ transplant recipients. Therefore, early recognition and treatment is essential in this population. Reference #1: Coussement J, Lebeaux D, et al. Nocardia Infection in Solid Organ Transplant Recipients: A Multicenter European Case-control Study. Clin Infect Dis 2016;63:338-345. Reference #2: Horl MP, Schmitz M, Ivens K, Grabensee B. Opportunistic infections after renal transplantation. Curr Opin Urol 2002;12(2):115-123. Reference #3: Wilmes D, Coche E, Rodriguez-Villalobos H, Kanaan N. Bacterial pneumonia in kidney transplant recipients. Resp Med 2018;137:89-94. DISCLOSURES: No relevant relationships by Jeannette Collins, source=Web Response No relevant relationships by Nikhil Huprikar, source=Web Response No relevant relationships by Paul Robben, source=Web Response

New Insights Into Cryptococcus Spp. Biology and Cryptococcal Meningitis.

Defective cell-mediated immunity is a major risk factor for cryptococcosis, a fatal disease if untreated. Cryptococcal meningitis (CM), the main presentation of disseminated disease, occurs through hematogenous spread to the brain from primary pulmonary foci, facilitated by yeast virulence factors. We revisit remarkable recent improvements in the prevention, diagnosis and management of CM. Cryptococcal antigen (CrAg), main capsular polysaccharide of Cryptococcus spp. is detectable in blood and cerebrospinal fluid of infected patients with point of care lateral flow assays. Recent World Health Organization guidelines recommend 7-day amphotericin B plus flucytosine, then 7-day high dose (1200mg/day) fluconazole for induction treatment of HIV-associated CM. Management of raised intracranial pressure, a consequence of CM, should rely mainly on daily therapeutic lumbar punctures until normalisation. In HIV-associated CM, following introduction of antifungal therapy, (re)initiation of antiretroviral therapy should be delayed by 4-6weeks to prevent immune reconstitution inflammatory syndrome, common in CM. CM is a fatal disease whose diagnosis has recently been simplified. Treatment should always include antifungal combination therapy and management of raised intracranial pressure. Screening for immune deficiency should be mandatory in all patients with cryptococcosis.