Today's Kaposi sarcoma is not the same as it was 40 years ago, or is it?

This review will provide an overview of the notion that Kaposi sarcoma (KS) is a disease that manifests under diverse and divergent circumstances. We begin with a historical introduction of KS and KS-associated herpesvirus (KSHV), highlight the diversity of clinical presentations of KS, summarize what we know about the cell of origin for this tumor, explore KSHV viral load as a potential biomarker for acute KSHV infections and KS-associated complications, and discuss immune modulators that impact KSHV infection, KSHV persistence, and KS disease.

Hiv-Related Kaposi Sarcoma in East Africa: Contemporary Update on Stage and Survival

Background: Stage at time of diagnosis and survival after diagnosis are critical parameters regarding the control of any cancer in any geographical setting. Unlike in resource-rich settings where publicly funded cancer surveillance routinely monitors these parameters, these data are non-existent through routine means in resource-limited areas. This is particularly relevant for Kaposi sarcoma (KS) in East Africa, for which recent changes in HIV treatment and chemotherapy guidelines as well as the COVID-19 pandemic dictate an update regarding stage and survival. Method(s): From October 2021 to August 2022, we evaluated HIV-infected adults (age >= 18 years) with a new diagnosis of KS made in 4 different primary care facilities (or their associated inpatient units) in Kenya and Uganda using a process of rapid case ascertainment. KS diagnosis was confirmed by pathology. Participants were examined, at time of biopsy, to document the extent of lesions and subsequently monitored longitudinally for vital status. Result(s): Among 180 HIV-infected adults identified with new onset KS, 31% were women, and the median (IQR) age was 35 (29-42) years. At time of KS diagnosis, 95% of the participants were taking ART, and the median (IQR) CD4+ T cell count was 197 (46-354) cells/mm3;46%, 20%, 11% and 23% had plasma HIV RNA of < 40, 40-1000, 1001-10,000 and >10,000 copies/ml, respectively. The median number of anatomic sites with KS lesions per participant was 7 (4-11);26% of participants had oral KS lesions that interfered with either eating or speaking, 74% had KS-associated edema, and 86% had ACTG stage T1 (advanced KS). Over a median follow-up of 2.6 months (IQR: 0.75 to 5.5), 56 participants died, and only 3 lost to follow-up. Cumulative incidence of death (95% CI), via Kaplan-Meier estimation, at 2 months, 6 months and 8 months following KS diagnosis was 24% (18%-31%), 33% (26%-42%), and 38% (29- 49%), respectively (Figure). Conclusion(s): In a recently assembled community-based sample of adults with newly-diagnosed HIV-related KS in East Africa, the majority have advanced KS at the time of KS diagnosis, and survival is poor. The findings are stark in absolute terms for the Treat-All era and unchanged from parameters obtained in the 5 years prior, indicating no improvement in these aspects of the control of KS in the region. Along with primary prevention of KS (i.e., reducing its incidence), novel approaches are needed for earlier detection, more efficient linkage to oncologic care, and more potent therapy. Survival Among Adults with HIV-Related Kaposi Sarcoma in East Africa.

A historical review of pandemics with a dermatological perspective

We present a literature review of dermatology features in historical pandemics. A pandemic is an epidemic occurring worldwide, or over a very wide area, crossing international boundaries and affecting a large number of people. Smallpox was the first documented pandemic, around 10 000 BC, spread by the inhalation of airborne droplets. A few days after an initial high fever, headache and fatigue, a mucocutaneous maculopapular eruption appeared, which then developed pustules and erosions. The last outbreak occurred in the USA in 1949. Smallpox was eradicated in 1980, following a vaccination programme. Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), an ongoing global pandemic. The earliest documentations were 3300 years ago. In 2020, the World Health Organization (WHO) provisionally estimated 1.5 million deaths globally. Most commonly affecting the lungs, cutaneous TB may present with inflammatory papules, plaques, suppurative nodules and chronic ulcers. Requiring long, complex antibiotic regimens, multidrug resistant TB is an increasing problem. Now extremely rare, yet still with recent outbreaks in 2021 in Madagascar, bubonic plague arrived in Europe in 1346 causing 75-200 million deaths. It is caused by the bacterium Yersinia pestis, transmitted through fleas that have fed on infected rodents. Clinical features include papules, pustules, ulcers and eschars, tender lymphadenopathy and systemic symptoms, and it responds to antibiotics. Syphilis, caused by the bacterium Treponema pallidum, is sexually transmitted. The first known outbreak was during warfare in 1494-5 in Naples, Italy. In 2020, the WHO estimated that, globally, seven million people had new infections. Primary syphilis typically produces a painless, genital ulcer (or chancre). Secondary syphilis presents with a nonitchy, maculopapular erythema over the trunk, palms and soles. Early recognition and antibiotic treatment usually lead to good outcomes. Estimated by the WHO to affect 37.7 million people in 2020, HIV is thought to have mutated from simian immunodeficiency virus by the 1960s in sub-Saharan Africa, spreading to the Caribbean and USA by the late 1960s. Initial symptoms include a fever, headache and lymphadenopathy. Dermatological features are common, including opportunistic cutaneous infections, nonspecific exanthemas, seborrhoeic dermatitis and Kaposi sarcoma. Advances in antiretroviral therapies mean people with HIV can have an excellent prognosis, although the WHO estimated in 2020 that more than 200 000 people with HIV died from concomitant TB. Since 2019, COVID-19 has had a considerable global impact on healthcare. With more than 300 million cases and 5.5 million deaths to date, some services have been overwhelmed owing to large case numbers, variable vaccine uptake, workplace changes to reduce transmission and staff shortages. Cutaneous features include perniosis, urticarial, purpuric, vesicular or maculopapular eruptions. Pandemics throughout history have been repeatedly shown to present with an element of skin involvement. We can utilize this to promote education and early recognition of these features, to facilitate diagnosis and raise awareness of the potential complications of serious diseases.

Melanized (dematiaceous) fungal infections simulating skin cancer in African organ transplant recipients

Fungi are the most frequent skin infections in organ transplant recipients (OTRs) and usually present as superficial mycoses. Deeper infections are much less common, potentially more serious and the incidence is higher in the first few months post-transplant. We report two African OTRs with deep fungal infections caused by dematiaceous (melanized, pigmented or black) fungi, who both presented with suspected skin malignancies. A 60-year-old Nigerian man developed a painful, ulcerated, amelanotic, bleeding nodule on his right fourth toe 2 months after renal transplantation. Clinical differential diagnoses included Kaposi sarcoma (KS), amelanotic acral melanoma and subungual squamous cell carcinoma (SCC). However, histology showed pseudoepitheliomatous hyperplasia, extensive mixed inflammation, multinucleated giant cells and pigmented septate hyphae with rounded 'budding' forms. Periodic acid-Schiff, Grocott and Masson-Fontana stains were positive, and Alcian blue stain was negative, consistent with infection by a dematiaceous fungus. Fungal 18S polymerase chain reaction (PCR) was positive and culture identified Nigrograna mackinnonii. Treatment with oral itraconazole was supervised virtually during the COVID-19 pandemic. After 6 months there was minimal response and he opted for amputation of the digit. A 61-year-old Nigerian man presented 2 months after renal transplantation with a 2-cm diameter nodule on his left thigh at the site of a previous burn. This failed to respond to antibiotics. Magnetic resonance imaging was suggestive of possible malignancy, but surgery was deferred because of the COVID-19 pandemic. Two months later the lesion was 5 cm in diameter and verrucous with an 8-cm sessile, purplish plaque on his right forearm. Atypical KS, lymphoma and chronic burns-associated SCC were all considered. However, histology from both lesions was similar to the first patient. Fungal culture and 18S PCR confirmed infection with the dematiaceous fungus Alternaria alternata. At his request, the right thigh lesion was excised. The lesion on his forearm has partially responded to 8 months of ongoing oral itraconazole. In our African OTR cohort, KS is more common than deep fungal infection. However, despite this suspicion of skin malignancy, both patients had phaeohyphomycoses caused by dematiaceous fungi. Characterized by the presence of melanin in their cell walls, > 130 species of these plant pathogens and soil saprophytes are implicated in human disease, particularly in immunocompromised individuals. Although localized skin diseases (phaeohyphomycoses, chromoblastomycosis and mycetoma) are the most common manifestations, rare disseminated, central nervous system and pulmonary infections may prove fatal. Although uncommon, deep fungal infection should be considered in atypical skin lesions in OTRs;histology, tissue culture and fungal PCR are critical to confirming this diagnosis.

Antiviral Potential of the Genus Panax: An updated review on their effects and underlying mechanism of action.

Viral infections are known as one of the major factors causing death. Ginseng is a medicinal plant that demonstrated a wide range of antiviral potential, and saponins are the major bioactive ingredients in the genus Panax with vast therapeutic potential. Studies focusing on the antiviral activity of the genus Panax plant-derived agents (extracts and saponins) and their mechanisms were identified and summarized, including contributions mainly from January 2016 until January 2022. P. ginseng, P. notoginseng, and P. quinquefolius were included in the review as valuable medicinal herbs against infections with 14 types of viruses. Reports from 9 extracts and 12 bioactive saponins were included, with 6 types of protopanaxadiol (PPD) ginsenosides and 6 types of protopanaxatriol (PPT) ginsenosides. The mechanisms mainly involved the inhibition of viral attachment and replication, the modulation of immune response by regulating signaling pathways, including the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway, phosphoinositide-dependent kinase-1 (PDK1)/ protein kinase B (Akt) signaling pathway, c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) pathway, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. This review includes detailed information about the mentioned antiviral effects of the genus Panax extracts and saponins in vitro and in vivo, and in human clinical trials, which provides a scientific basis for ginseng as an adjunctive therapeutic drug or nutraceutical.

Immune Reconstitution Inflammatory Syndrome Presenting as Disseminated Kaposi Sarcoma.

We present a patient who was previously diagnosed with HIV and had multiple violaceous skin lesions at the time of his diagnosis. Following the initiation of antiretroviral therapy (ART), the number of lesions increased significantly and he developed shortness of breath, which prompted hospital admission for further workup. Biopsy of the skin lesions confirmed the diagnosis of Kaposi sarcoma (KS). Bronchoscopy with biopsy revealed KS lesions in his respiratory system. Imaging and biopsy confirmed KS invasion of lymph nodes. Due to widespread KS, he was diagnosed with immune reconstitution inflammatory syndrome (IRIS). Because of the lack of improvement on ART alone, he was started on chemotherapy, which decreased the size of existing skin lesions, stalled the development of new skin lesions, and led to symptom improvement. As a result of this case, we recommend that treatment teams have close follow-ups of patients started on ART and that they remain mindful of the possibility of IRIS. Disseminated KS may warrant a prompt response with chemotherapy to improve outcomes.

Glucose and mannose analogs inhibit KSHV replication by blocking N-glycosylation and inducing the unfolded protein response.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent for Kaposi's sarcoma (KS), an HIV/AIDS-associated malignancy. Effective treatments against KS remain to be developed. The sugar analog 2-deoxy- d-glucose (2-DG) is an anticancer agent that is well-tolerated and safe in patients and was recently demonstrated to be a potent antiviral, including KSHV and severe acute respiratory syndrome coronavirus 2. Because 2-DG inhibits glycolysis and N-glycosylation, identifying its molecular targets is challenging. Here we compare the antiviral effect of 2-DG with 2-fluoro-deoxy- d-glucose, a glycolysis inhibitor, and 2-deoxy-fluoro- d-mannose (2-DFM), a specific N-glycosylation inhibitor. At doses similar to those clinically achievable with 2-DG, the three drugs impair KSHV replication and virion production in iSLK.219 cells via downregulation of viral structural glycoprotein expression (K8.1 and gB), being 2-DFM the most potent KSHV inhibitor. Consistently with the higher potency of 2-DFM, we found that d-mannose rescues KSHV glycoprotein synthesis and virus production, indicating that inhibition of N-glycosylation is the main antiviral target using d-mannose competition experiments. Suppression of N-glycosylation by the sugar drugs triggers ER stress. It activates the host unfolded protein response (UPR), counteracting KSHV-induced inhibition of the protein kinase R-like endoplasmic reticulum kinase branch, particularly activating transcription factor 4 and C/EBP homologous protein expression. Finally, we demonstrate that sugar analogs induce autophagy (a prosurvival mechanism) and, thus, inhibit viral replication playing a protective role against KSHV-induced cell death, further supporting their direct antiviral effect and potential therapeutic use. Our work identifies inhibition of N-glycosylation leading to ER stress and UPR as an antienveloped virus target and sugar analogs such as 2-DG and the newly identified 2-DFM as antiviral drugs.

Impact of COVID-19 pandemic in the care of people living with HIV and cancer at an oncologic center in Mexico.

BACKGROUND: People living with HIV(PLWH) and cancer are among the most vulnerable patients and require constant access to medical services. We compared the characteristics of PLWH and cancer in Mexico, before and during the COVID-19 pandemic. METHODS: Patients admitted 1 year before (pre-pandemic) and 1 year after the start of the pandemic (pandemic) were included. Clinical characteristics, HIV-related variables, and 90-day mortality were compared. Data are described a proportions (N,%) and central tendency measures. A multiple regression model for variables associated with 90-day mortality was performed. RESULTS: Seventy-nine patients were seen in the pre-pandemic period; 92 during the pandemic. Main diagnoses were Kaposi Sarcoma and lymphoma. CD4+ cell count at diagnosis was lower during the pandemic: 81 cells/mm3 vs. 128 cells/mm3, p = .035. CD4+<100 cells/mm3 at first consultation increased from 41% to 58% during the pandemic (p = .041). Only BMI <20 kg/m2 was associated to death (aOR 8.27, 95%CI 1.74-39.25) (p = .008). The pandemic period was not associated with a higher 90-day mortality. CONCLUSIONS: PLWH and cancer presented to care with advanced disease overall. This was more pronounced during the pandemic period. Mortality was associated with AIDS-related variables regardless of study period. This underscores the need for strategies to maintain in-person access to health-care services for PLWH.

COVID-19 in a patient with HIV and Kaposi sarcoma

A 53 year old male diagnosed with HIV, SARS-CoV-2 and Kaposi sarcoma developed a purple-brown maculopapular rash on the left calf approximately 6 months before hospitalization and was diagnosed with venous ulcer. The lesions grew in size, spread on the whole body and also appeared on the palate. During this time the patient did not ask for a second opinion and was not monitored by a medical specialist. In De-cember 2020, he developed a severe form of COVID-19 with acute respiratory failure and was admitted to the hospital. He was simultaneously diagnosed with HIV and severe immunosuppression. The skin biopsy confirmed Kaposi sarcoma in the nodular stage. Antiretroviral therapy (ART) was initiated and the patient later received liposomal doxorubicin chemotherapy. The patient slowly recovered whilst showing improvement of his clinical condition and immunological status. © 2021, Amaltea Medical Publishing House. All rights reserved.

Detection of SARS-CoV-2 and HHV-8 from a large pericardial effusion in an HIV-positive patient with COVID-19 and clinically diagnosed Kaposi sarcoma: a case report.

BACKGROUND: Pericardial effusion is a late manifestation of HIV more commonly observed in individuals with depressed CD4 counts. Although Mycobacterium tuberculosis remains to be one of the most frequently identified pathogens in the pericardial fluid among people living with HIV, less commonly described etiologies include SARS-CoV-2 that causes coronavirus disease and human herpesvirus-8 which is associated with Kaposi sarcoma. Isolation of more than one pathogen in normally sterile sites remains challenging and rare. We report the first documentation of both SARS-CoV-2 and HHV-8 in the pericardial fluid. CASE PRESENTATION: We present the case of a young man in his 20s with a recent history of clinically diagnosed pulmonary tuberculosis who was admitted for progressive dyspnea and cough. He had multiple violaceous cutaneous lesions on the face, neck, and trunk and diffused lymphadenopathies. He tested positive for SARS-CoV-2 on admission. The patient was clinically diagnosed with pneumonia, Kaposi sarcoma, and HIV/AIDS. Empiric broad spectrum antimicrobial regimen was subsequently initiated. HIV with low CD4 count was confirmed during hospitalization. Echocardiography revealed a large pericardial effusion, in impending cardiac tamponade. Frond-like fibrin strands, extending to the parietal pericardium, were also observed. Pericardiostomy yielded hemorrhagic, exudative effusion with lymphocytic predominance. SARS-CoV-2 and HHV-8 were detected in the pericardial fluid, and bacterial, fungal, and tuberculous studies were negative. The patient had clinical improvement after pericardial drainage. However, despite our best clinical care, he developed a nosocomial infection leading to clinical deterioration and death. CONCLUSION: Detection of SARS-CoV-2 and HHV-8 in the pericardial fluid is rare, and interpretation of their significance in clinical care is challenging. However, coronavirus disease and Kaposi sarcoma must be considered and adequately addressed in immunocompromised adults presenting with large pericardial effusion.

LESIONS MIMICKING KAPOSI SARCOMA IN A WOMAN LIVING WITH HIV FOLLOWING PFIZER-BIONTECH COVID- 19 VACCINATION

Introduction A spectrum of skin reactions following mRNA COVID vaccinations have been reported that can mimic dermatological manifestations of Human Immunodeficiency Virus (HIV) infection. Case Description A 47-year-old Zimbabwean female living with HIV since 2011 (nadir CD4 366 cells/mm3) was seen in our HIV clinic with a widespread rash and raised, itchy lesions over her body measuring approximately 5-7mm which appeared three weeks after her first Pfizer-BioNTech COVID-19 vaccine. There was no systemic involvement. Her CD4 count was 641 cells/mm3 (44%) with a fully suppressed viral load on antiretroviral therapy since June 2015 with no other pertinent medical history. There was no response to topical anti-fungal therapy but symptomatic relief with anti-pruritic and anti-histamine was noted. Treatment with oral erythromycin 500mg four times a day for two weeks decreased the size of the lesions and improved the rash. A punch biopsy of pale brown skin at this time was performed with appearances in keeping with those of a lichenoid pattern of inflammation. Our patient continues to improve with erythromycin.Topical or systemic corticosteroid therapy can be considered to further ameliorate her condition. Discussion Lichenoid drug eruptions are well recognized. Our case demonstrates such a reaction to the Pfizer-BioNTech COVID-19 vaccination which adds to cases described in the contemporary medical literature. It is vital to recognize this complication in our specialty as lesions may mimic lichen planus clinically and histologically and may be mistaken for dermatological manifestations associated with HIV, including Kaposi Sarcoma (KS) and bacillary angiomatosis, which can manifest regardless of immune status.

Pulmonary Kaposi Sarcoma as an Unusual Etiology of Acute Hypoxemic Respiratory Failure in the Era of Highly Active Antiretroviral Therapy: A Case Report.

Kaposi sarcoma (KS) is caused by human herpesvirus 8 (HHV-8). Epidemic KS is described in the human immunodeficiency virus (HIV) population with acquired immune deficiency syndrome (AIDS). It primarily affects the skin, but it may uncommonly disseminate to involve extracutaneous sites such as the gastrointestinal (GI) tract, liver, and lungs. In this case report, the authors report a 26-year-old homosexual male who was admitted with acute hypoxemic respiratory failure. He was diagnosed with an HIV infection about five months before index presentation, and he was commenced on highly active antiretroviral therapy (HAART). Physical examination was remarkable for diffuse cutaneous nodules over the lower extremities, back, and oropharynx. Chest imaging revealed diffuse bilateral infiltrates, mediastinal adenopathy, and a persistent bilateral pleural effusion. Extensive diagnostic workup was negative for underlying infectious etiology. Transbronchial biopsy demonstrated proliferated spindle cells that stained positive for HHV-8 in keeping with pulmonary KS. Skin biopsies also concurred with the diagnosis of cutaneous KS. Interestingly, the cluster of differentiation 4 (CD4) count was 647 cells/mm3, and HIV viral load (VL) was 500 copies/ml. This case demonstrated an atypical natural history of pulmonary KS in an HIV patient as pulmonary and disseminated mucocutaneous KS occurred with a relatively higher CD4 count (≥500 cells/mm3). It also reminds pulmonologists and infectious disease specialists to consider pulmonary KS as a differential diagnosis of acute hypoxemic respiratory failure in HIV patients, even in the absence of other clinical and laboratory criteria that define the AIDS stage.

Pulmonary Kaposi Sarcoma without Respiratory Symptoms and Skin Lesions in an HIV-Naïve Patient: A Case Report and Literature Review.

Kaposi sarcoma (KS) is a multifocal lympho-angioproliferative, mesenchymal low-grade tumor associated with a γ2-herpesvirus, named Kaposi sarcoma-associated virus or human herpesvirus (KSHV/HHV8). The lung is considered a usual anatomical location of KS, despite being infrequent, often in association with extensive mucocutaneous lesions and very uncommonly as an isolated event. We report a case of a pulmonary KS (pKS) in a human immunodeficiency virus (HIV) naïve patient, which was atypical due to a lack of cutaneous involvement and an absence of respiratory symptoms. The pKS was initially identified as a tumoral suspected nodular lesion and only after immunohistochemical analysis was it characterized as KS. Furthermore, the diagnosis of pKS led to the discovery of the HIV-seropositive status of the patient, previously unknown. Our report underlines the importance of considering pKS even without skin lesions and as a first manifestation of HIV infection. We also reviewed literature on the current knowledge about pKS in people living with HIV (PLWH) to underline how one of the most common HIV/acquired immunodeficiency syndrome (AIDS) associated tumors can have a challenging localization and be difficult to recognize.

Adrenal Insufficiency: A Unique Presentation of Multicentric Castleman Disease with Human Herpes Virus 8 Positivity and Concomitant Kaposi Sarcoma

Introduction: Multicentric Castleman Disease (MCD) is a lymphoproliferative disorder involving multiple lymph nodes and can be associated with human herpes 8 virus (HHV-8). Hyaline vascular (HV) MCD is rare, occurring in < 10% of cases. MCD with concomitant HIV negative Kaposi Sarcoma (KS) is also uncommon and can peculiarly present with adrenal insufficiency. Case Description: 53-year-old male with biopsy proven diagnosis of HHV-8 positive KS was transferred to our institution with persistent hypotension requiring pressor support. He described a two-week history of night sweats, 20 Ib weight & appetite loss, fatigue, muscles aches, and subjective fevers. Vitals: BP: 99/50 mmHg, HR: 90 bpm, RR: 19 and T: 103oF. Physical exam revealed multiple violaceous, non-blanching plaques on his body, tender inguinal & axillary lymphadenopathy, and bilateral lower extremity edema. Initial labs: Na: 137 mmol/L, K: 3.6 mmol/L, WBC: 5.6 k/uL, Hg: 7.1 gm/dL, Hct: 21%, Plt: 91 k/uL, AM cortisol: 12.5 mcg/dL (5.3-22.5), ACTH < 1 pg/mL, TSH: 7.5 uIU/mL, FTF: 0.63 ng/dL, PRL: 7 ng/mL, Total testosterone: 20 ng/dL, FSH: 4.2 mIU/mL, LH: 8.3 mIU/mL, IGF-1: 77 ng/mL (64-218), ESR >85 mm/hr (< 20), and CRP: 76 mg/dL (< 3). HIV and COVID-19 tests were negative. He was started on oral Levothyroxine and IV Hydrocortisone with significant improvement in his BP leading to discontinuation of pressor support. CT chest/abdomen/pelvis showed diffuse lymphadenopathy consistent with KS with normal adrenal glands. Left axillary lymph node biopsy revealed HV MCD. Additional labs;IL-6: 11.5 pg/mL (< 2), IgG4: 45 mg/dL (1-123), normal CD4 count, renin and aldosterone levels. 21 alpha hydroxylase antibody, T-spot, extensive autoimmune and infectious work-up were negative. Pituitary MRI could not be obtained due to a metal object behind his right orbit. Head CT was negative for pituitary abnormality. He failed his ACTH stimulation test with cortisol level: 13 mcg/dL at 90 minutes (baseline ACTH was not obtained). Thus, he was discharged on physiological oral Hydrocortisone upon clinical improvement. He began chemotherapy 1 week post discharge, however he succumbed to his disseminated and aggressive disease 20 days later. Discussion: MCD with concomitant KS is a rare and rapidly progressive disease which can cause death within weeks. IL-6 overproduction is thought to be associated with its symptom progression. Worse clinical outcomes are correlated with HIV or HHV-8 positivity. It can uncommonly be associated with either primary or secondary adrenal insufficiency requiring prompt evaluation and treatment with systemic steroids to prevent development of adrenal crisis.

COVID-19 infection and mortality in patients with skin malignancies receiving systemic anti-cancer therapy (SACT): The Guy's Cancer Centre experience

Background: The COVID-19 pandemic has influenced treatment decisions in cancer patients. There is increasing evidence that not all oncology patients are at increased risk of COVID-19 infection or death. This study aimed to look at rate of SARS-CoV-2 infection and mortality in patients with skin malignancies receiving systemic anti-cancer therapy (SACT) during the pandemic in Guy's Cancer Centre. Methods: All patients with skin cancer receiving SACT at Guy's Cancer Centre between March 1st and May 31st 2020 were included. Demographic data: sex, age, socio-economic status (SES), ethnicity, comorbidities, medications and smoking history were collected along with cancer characteristics: cancer type, stage, treatment paradigm, modality and line. COVID-19 infection was confirmed by PCR and severity defined by the World Health Organisation classification. Patients with radiological or clinical diagnoses alone were excluded. Results: Of 116 skin cancer patients on SACT over the 3-month period, 89% had Melanoma, 5% Kaposi's Sarcoma (KS), 3% Squamous Cell, 2% Merkel Cell, 1% Basal Cell Carcinoma and 1% Angiosarcoma. 53% were male and 78% were of low SES. 62% were being treated with palliative intent and 70% of these were on first line palliative treatment. The median age was 57.6 years in COVID-19 positive patients (n=3) compared to 60.3 years in the negative group (n=113). 58.6% received immunotherapy, 28.4% targeted therapy, 7.8% chemotherapy and 4.3% combined treatment. Of the 3 patients (2.6%) with confirmed COVID-19 infection, the two patients with KS were receiving liposomal doxorubicin hydrochloride and the other paclitaxel chemotherapy and the patient with Melanoma was receiving encorafenib and binimetinib. All COVID-19 positive patients were of low SES, 2 females and 1 male. There was a low rate of co-morbidities with hypertension in 1 COVID-19 positive patient and none in the negative group. All 3 confirmed COVID-19 patients developed severe pneumonia and were diagnosed within 7 days of the onset of symptoms. There were no COVID related deaths and one disease-related death in the negative cohort. Conclusion: There was a low rate of COVID-19 infection in the 116 skin cancer patients on SACT (2.6%) with 60% of patients on immunotherapy. All 3 confirmed cases had severe pneumonia with no COVID-19 related deaths (0%);2 were receiving chemotherapy and 1 on targeted therapy. Patients on treatment were encouraged to shield between hospital attendances during this period which may account for the reduced rate of SARS-CoV-2 infection. This data supports the emerging observations that immunotherapy does not confer an increased risk of severe COVID-19 infection in cancer patients. This observation is confounded by the relatively young age and low co-morbidity rates in the cohort which may have contributed to the low infection and mortality rate.

Environmental determinants of Kaposi's sarcoma-associated herpesvirus (KSHV) transmission in rural Uganda (ENDKU study): Contributions to research on KSHV infection and reactivation in African children; A longitudinal cohort study.

BACKGROUND: The Environmental Determinants of KSHV transmission in rural Uganda (ENDKU) study began enrollment in February 2020 with the purpose of defining the relationship between malaria, primarily caused by Plasmodium falciparum in sub-Saharan Africa, and KSHV susceptibility and reactivation. Uganda is an ideal study site, because both malaria and KSHV are endemic and widespread, even among young children. METHODS: ENDKU is a longitudinal cohort study of infants enrolled at six months of age and followed until three years of age. The main study, and one smaller sub-study, is nested within the General Population Cohort (GPC), a long-standing population cohort in rural Uganda. The ENDKU study was created to test the hypothesis that P. falciparum malaria increases an infant's susceptibility to KSHV infection. A sub-study to evaluate the effects of P. falciparum on KSHV reactivation involves an additional cohort of 5-10-year-old children with and without acute malaria who presented to the GPC study clinic. For each study, participants provided demographic and behavioral data through administered questionnaires and blood and saliva samples. RESULTS: Despite barriers presented by the COVID-19 pandemic, the study team was able to leverage the long-standing relationship of the UK Medical Research Council and the Uganda Virus Research Institute (MRC/UVRI) with the community, a strong commitment to research, and a multi-disciplinary team of experts to successfully implement the ENDKU study. CONCLUSION: The results of this multi-pronged approach will answer important questions about the etiology and transmission of KSHV in sub-Saharan Africa and the data and samples collected will be an important future resource for scientific research in the region.

Disseminated Kaposi sarcoma following COVID-19 in a 61-year-old Albanian immunocompetent man: a case report and review of the literature.

BACKGROUND: COVID-19 and its related anti-inflammatory treatment (steroids, immunomodulators) may induce the reactivation of latent bacterial, parasitic, and viral infections. According to our knowledge, no case of disseminated HHV-8-related Kaposi sarcoma (KS) after COVID-19 and its treatment has been described so far. Only one case of cutaneous KS concurrently with COVID-19 has been previously reported. CASE PRESENTATION: We describe a case of disseminated KS in a 61-year-old immunocompetent Albanian man after hospitalization for COVID-19. METHODS FOR LITERATURE RESEARCH: We used PubMed as biomedical database for the literature research. We selected keyword combinations including "Kaposi sarcoma," "HHV-8," "immunocompetent," "COVID-19," "SARS-CoV-2," and "steroids." No time or language limitation was set. Titles and abstracts of selected articles were systematically screened. Articles were included in the examination if they were published under free access through the digital library of the University of Brescia (Italy), and provided full text. Articles were excluded if the topic was beyond the aim of our study. Finally, we selected 15 articles. RESULTS: We describe a case of KS in COVID-19 patient and postulate that Interleukin-6 (IL-6) activity and steroid-induced immunodeficiency may play a major role in KS emergence. No published case of disseminated KS following COVID-19 in otherwise healthy individuals was found through the systematic literature review, despite the high incidence of COVID-19 in areas with medium-high prevalence of HHV-8 infection. This observation might be explained by the role of individual genetic susceptibility factors. CONCLUSIONS: SARS-CoV-2 infection and its treatment may lead to reactivation of several latent infections, including HHV-8 and its related clinical syndrome, Kaposi sarcoma.

DIAGNOSING KAPOSI'S SARCOMA IN ABSENCE OF CUTANEOUS LESIONS IN THE HAART ERA

TYPE: Case Report TOPIC: Chest Infections INTRODUCTION: Kaposi sarcoma (KS) is very commonly associated with Human Immunodeficiency Virus (HIV) infection. The clinical course of HIV associated KS could be indolent with muco-cutaneous or aggressive with visceral organ system involvement. It is extremely uncommon for the visceral involvement to occur in the absence of mucocutaneous manifestations. CASE PRESENTATION: A 45-year male with HIV, presented with fatigue, exertional dyspnea, cough. Vital signs showed low grade fever and hypoxia. On physical exam the pertinent positive finding was diffuse inspiratory crackles. The CT chest showed multiple irregular nodular infiltrates in the lungs. Blood and sputum cultures were collected, and the patient was started on empiric antibiotics and fluconazole. The viral load and the absolute CD4 count were 64,360 and 17, respectively. The transesophageal echocardiogram was negative for vegetations. SARS-COVID19, blood culture and three sputum acid fast bacilli were negative. The patient continued to worsen. The bronchoscopy showed a friable mass in the left lower trachea. The immunohistochemistry analysis of the lesions was positive for CD34, CD31, HHV-8, FLI-1 which was diagnostic of KS. The patient was started on Highly Active Antiretroviral Therapy (HAART) and was discharged on HAART with a scheduled follow up. DISCUSSION: The introduction of HAART has decreased the incidence of KS to 0.03 per 1000 patient years in the HAART era. 15.5 % of patients have pulmonary KS in the absence of mucocutaneous lesions. These rates of pulmonary KS in autopsy findings were noted in the pre-HAART era. CONCLUSIONS: To establish a diagnosis of pulmonary KS in the absence of the characteristic cutaneous lesions is challenging. DISCLOSURE: Nothing to declare. KEYWORD: Kaposi Sarcoma

New-onset cutaneous kaposi's sarcoma following SARS-CoV-2 infection.

BACKGROUND: COVID-19 is associated with several cutaneous manifestations, including chilbain-like lesions, urticaria, erythema multiforme, and maculopapular lesions. Dermatoses may be directly linked to the viral infection or also represent a consequence of systemic therapies administrated for COVID-19. A potential role of SARS-CoV-2 in triggering the reactivation of other viruses, such as HHV-6, HHV-7 and Epstein-Barr virus has been hypothesized. OBJECTIVE: To better understand and hypothesize possible pathogenetic correlations of COVID-19 with other dermatological conditions. METHODS: We report the case of an 83-year-old woman hospitalized in a nursing home for several years. On November 2020, the patient had been diagnosed with SARS-CoV-2 infection, with repeated positive swabs until January 2021. After a month, new-onset asymptomatic cutaneous purplish macular lesions and violaceous patches occurred bilaterally on the feet. RESULTS: An incisional cutaneous biopsy and the histological examination of the plantar lesion revealed the diagnosis of Kaposi Sarcoma. CONCLUSION: We report a unique case of new-onset bilateral Kaposi's sarcoma following COVID-19, speculating on a possible role of SARS-CoV-2 in the reactivation of human herpes virus-8 (HHV-8) infection.