Visceral Involvement Research Articles

Pembrolizumab in combination with gemcitabine for patients with HER2-negative advanced breast cancer: GEICAM/2015–04 (PANGEA-Breast) study

BackgroundWe evaluated a new chemoimmunotherapy combination based on the anti-PD1 monoclonal antibody pembrolizumab and the pyrimidine antimetabolite gemcitabine in HER2- advanced breast cancer (ABC) patients previously treated in the advanced setting, in order to explore a potential synergism that could eventually obtain long term benefit in these patients.MethodsHER2-negative ABC patients received 21-day cycles of pembrolizumab 200 mg (day 1) and gemcitabine (days 1 and 8). A run-in-phase (6 + 6 design) was planned with two dose levels (DL) of gemcitabine (1,250 mg/m2 [DL0]; 1,000 mg/m2 [DL1]) to determine the recommended phase II dose (RP2D). The primary objective was objective response rate (ORR). Tumor infiltrating lymphocytes (TILs) density and PD-L1 expression in tumors and myeloid-derived suppressor cells (MDSCs) levels in peripheral blood were analyzed.ResultsFourteen patients were treated with DL0, resulting in RP2D. Thirty-six patients were evaluated during the first stage of Simon’s design. Recruitment was stopped as statistical assumptions were not met. The median age was 52; 21 (58%) patients had triple-negative disease, 28 (78%) visceral involvement, and 27 (75%) ≥ 2 metastatic locations. Progression disease was observed in 29 patients. ORR was 15% (95% CI, 5–32). Eight patients were treated ≥ 6 months before progression. Fourteen patients reported grade ≥ 3 treatment-related adverse events. Due to the small sample size, we did not find any clear association between immune tumor biomarkers and treatment efficacy that could identify a subgroup with higher probability of response or better survival. However, patients that experienced a clinical benefit showed decreased MDSCs levels in peripheral blood along the treatment.ConclusionPembrolizumab 200 mg and gemcitabine 1,250 mg/m2 were considered as RP2D. The objective of ORR was not met; however, 22% patients were on treatment for ≥ 6 months. ABC patients that could benefit of chemoimmunotherapy strategies must be carefully selected by robust and validated biomarkers. In our heavily pretreated population, TILs, PD-L1 expression and MDSCs levels could not identify a subgroup of patients for whom the combination of gemcitabine and pembrolizumab would induce long term benefit.Trial registrationClinicalTrials.gov and EudraCT (NCT03025880 and 2016–001,779-54, respectively). Registration dates: 20/01/2017 and 18/11/2016, respectively.

Progressive aortic enlargement in medically managed acute type B aortic dissections with visceral aortic involvement.

Aortic remodeling of the thoracic aorta has been studied in patients treated with medical or endovascular therapy for the treatment of acute aortic dissections; however, particular attention has not yet focused on identifying specific growth patterns and rates across all aortic zones. Additionally, previous studies have not delineated between dissections with and without visceral aortic involvement, and we hypothesize that these two cohorts may exhibit distinct differences. The aim of this study is to investigate aortic behavior over time in medically managed acute Society for Vascular Surgery/Society of Thoracic Surgeons (SVS/STS) type B dissections with visceral aortic involvement and identify potential associations of subsequent aortic behavior with clinical outcomes. A single-center retrospective review was performed of all patients between 2010 and 2020 with acute SVS/STS type B aortic dissections with visceral aortic involvement that were not surgically managed. Short-axis centerline measurements of the true/false lumen and total aortic diameter (TAD) were taken at standardized locations relative to aortic anatomy within each aortic zone, including nondissected zones. Measurements were taken at the time of diagnosis and at six subsequent yearly intervals. Diameter changes over time were evaluated using repeated measures mixed models linear growth analysis. Aortic enlargement was classified by growth in TAD ≥5mm in either the thoracic (thoracic segment enlargement [TSE], zone 0-4) or visceral segments (visceral segment enlargement [VSE], zone 5-9). A total of 78 patients were identified with a median length of follow-up of 3.3years (interquartile range [IQR], 1.3-6.6years). Follow-up past 5years was seen in 31% of the cohort. For the entire cohort, mean thoracic growth in TAD was 2.0± 2.0mm/year, and visceral growth in TAD was 2.5± 2.4mm/year. TSE was observed in 65% of patients, with a median time until onset of 0.8years (IQR, 0.4-2.3years). VSE was observed in 57% of the cohort, with a median time until onset of 1.6years (IQR, 0.9-3.3years). Repeat measures mixed models linear growth analysis identified significant predictable linear growth in all aortic zones except for the nondissected zones 0-2. Odds for TSE are significantly increased in patients with known genetically triggered aortic conditions (odds ratio [OR], 2; 95% confidence interval [CI], 1.8-4.5; P= .044) and in cases where the dissection entry tear was in either zone 1 or 2 (OR, 4.8; 95% CI, 1.2-8.4; P= .044). In adjusted regression analysis, odds for intervention in the thoracic aorta were significantly increased in patients with rapid TSE in zone 3 (OR, 3.6; 95% CI, 1.1-8.4; P= .045). Similarly, odds for intervention targeting the visceral aortic segment were significantly increased in patients with zone 9 VSE (OR, 9.3; 95% CI, 1.1-13.3; P= .014). Odds for 5-year all-cause mortality were significantly increased in cases with large thoracic aneurysms (OR, 6.1; 95% CI, 1.1-14.9; P= .042). Aortic enlargement was present in the majority of patients with medically managed acute SVS/STS Type B aortic dissections with visceral aortic involvement, with analysis demonstrating predictable linear growth in all dissected zones. Patients with aortic enlargement demonstrated higher gross changes in diameter in addition to higher yearly rates of change compared with all comers. Odds for enlargement were impacted by both patient demographic and anatomic dissection characteristics. Growth in zone 3 and zone 9 significantly increased odds for aortic intervention. Odds for 5-year mortality were significantly increased in the presence of large thoracic aneurysms. Results highlight risk of progressive degeneration beyond acute phase in SVS/STS Type B aortic dissections with visceral aortic involvement, with life-long surveillance remaining crucial in management of dissections.

Excision of triple compartment deep infiltrating endometriosis with visceral involvement

Background: Excision of multi-compartment deep infiltrating endometriosis with visceral involvement is challenging. We illustrate an interdisciplinary approach to complete minimally invasive excision in a single surgery. Case: We present a case of deep infiltrating endometriosis with visceral involvement in the anterior, middle, and posterior compartments. A collaborative surgical approach was taken with gynecologic, colorectal, and urologic surgeons to perform a robot-assisted total laparoscopic hysterectomy, bilateral salpingectomy, ovarian cystectomy, and unilateral oophorectomy with concurrent segmental resection of rectosigmoid and excision of transmural bladder and vaginal nodules. Conclusion: Thorough preoperative evaluation and an interdisciplinary approach to surgical planning involving radiology, gynecology, colorectal surgery, and urology allowed for complete simultaneous resection of bladder, rectosigmoid, and pelvic deep infiltrating endometriosis without complications via a minimally invasive route.

Progressive aortic enlargement in medically managed acute type B aortic dissections with visceral aortic involvement: Presented at the 2022 Vascular Annual Meeting of the Society for Vascular Surgery, Boston, MA, June 15-18, 2022.

Progressive aortic enlargement in medically managed acute type B aortic dissections with visceral aortic involvement: Presented at the 2022 Vascular Annual Meeting of the Society for Vascular Surgery, Boston, MA, June 15-18, 2022.

An uncommon diagnosis of a common clinical presentation – Visceral Niemann–Pick disease

Niemann–Pick (NP) disease is a diverse spectrum of disorders, autosomal recessive in nature, characterized by failure to thrive, visceral involvement in the form of hepatosplenomegaly and neurodegenerative changes. It is caused by an inherited deficiency of acid sphingomyelinase enzyme, leading to deposition of sphingomyelin and cholesterol within the lysosome of reticuloendothelial cells of various organs. We present a 16-month-old developmentally normal, well-grown girl with progressive, insidious onset abdominal distension, and no other symptoms. She was initially misdiagnosed as sepsis, but, on further evaluation was found to be genetically proven NP disease with autosomal recessive inheritance with sphingomyelin phosphodiesterase-1 gene positivity.

Primary Cutaneous Gamma-Delta T-Cell Lymphoma (PCGDTCL) Descriptors and Clinicopathologic Determinants of Survival: Analysis of a Pooled Database

Introduction Primary Cutaneous Gamma-Delta T-cell Lymphoma (PCGDTL) is a rare clinical entity that represents <1% of all cutaneous lymphomas. It is characterized by clonal proliferation of mature, activated T-cells expressing the T-cell receptor (TCR) γ/δ and cytotoxic molecules. PCGDTL is often resistant to conventional chemotherapy and is usually associated with poor prognosis. We have conducted this pooled database analysis to delineate key disease characteristics and clinicopathologic determinants of survival in this rare cutaneous T-cell lymphoma. Methods To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 140 cases. Kaplan-Meier survival curves were constructed. Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results A total of 140 patients with confirmed PCGDTCL were identified. The median age was 54 years with peak incidence between ages 52 and 65 years. There was no sex preponderance. The median duration of symptoms prior to diagnosis was 9 months. Eighty percent of patients presented with >4 lesions with an average size of 3.4cm. The disease involved mostly the lower extremities followed by the upper extremities, trunk, and lastly the face. Almost all the lesions involved the dermis with 48% involving the epidermis. Twenty-four percent of the lesions presented with ulceration and 30% had fat necrosis. Patients presented with constitutional symptoms in 28%, splenomegaly 6%, lymphadenopathy 16%, and hemophagocytic syndrome (HPS) 13%. Compared to no treatment, combination chemotherapy and stem cell transplant (SCT) were statistically superior with median OS months of 2, 16, and not reached respectively (p<0.0001). Age inversely correlated with survival while time from symptoms to diagnosis has a positive correlation. CD30+ imparted a survival advantage while HPS was detrimental to OS, both at borderline significance. Visceral involvement was also associated with a worse median OS (9.5 vs 18 months). OS was not impacted by sex, size of the lesions, or subcutaneous involvement. While solitary disease and absence of constitutional symptoms and bone marrow involvement seemed to have better OS, they did not reach statistical significance. Conclusions This study presents an updated clinicopathologic data from a pooled cohort of patients with PCGDTCL. It details the features of this rare disease and identifies the clinical, immunohistochemical, and treatment modalities that are major determinants of OS.

Characterizing Outcomes in Visceral Cutaneous T-Cell Lymphoma: A Real-World Retrospective Study

Introduction: Visceral Cutaneous T-Cell Lymphoma (vCTCL) is a rare and understudied complication of CTCL. Visceral involvement is associated with a poor prognosis, with a median survival of less than 1.5 years. We aimed to assess clinical characteristics, treatment, and outcomes associated with vCTCL. Methods: We conducted a retrospective review of patients with vCTCL from a CTCL database of 656 patients seen at the Winship Cancer Institute at Emory University from 1990-2022. vCTCL was defined as stage 4B or M1 disease that was pathologically confirmed or clinically suspected. Clinical data collected from the electronic medical record included baseline demographics, disease characteristics, pathologic characteristics, laboratory values, and treatment patterns. Descriptive analysis was performed for covariates. Clinical outcomes were measured as overall survival (OS) and progression-free survival (PFS) using the Kaplan-Meier method and univariable Cox regression analysis. Statistical analysis was performed using SAS with significance at the 0.05 level. Results: Twenty-six patients had vCTCL of which 42.3% were black and 57.7% were white. There was an even distribution among male (53.8%) and female patients (46.2%) [Table 1]. Median age at diagnosis of vCTCL was 58.5 years (47-66). Eight patients (30.8%) had ECOG PS ≥2. The most common diagnosis was mycosis fungoides (73.1%) and Sézary syndrome (11.5%), others being primary cutaneous anaplastic large cell (n=1), cytotoxic T cell (n=1), and gamma-delta T cell lymphoma variants (n=1). At the time of initial diagnosis, TNMB stage was 1B in 7 patients (33.3%), 2A/2B in 6 (28.6%), 3A in 2 (9.5%), 4A1/A2 in 4 (19%), and 4B in 7 (33.3%). Four patients (15.4%) had N2 involvement and 8 patients (30.8%) had N3 involvement. Eight patients had stage B2 disease (30.8%). Approximately half of the cohort had large cell transformation (LCT) with 61.5% having concurrent biopsy-proven LCT with visceral metastasis. Eleven patients (60%) had matched skin and blood TCR positivity. Twenty-three patients had biopsy-proven vCTCL with the most common sites being lung (42.3%), liver (19.2%), bone marrow (11.5%), and CNS (11.5%). Nine patients (34.6%) had at least 2 sites of metastases. Liver metastases were associated with a higher rate of subsequent disease progression (HR 3.29, p=0.031). Other metastases (23%) involving the thyroid, kidney, pleural or peritoneal compartments were associated with decreased survival (HR 8.91, p<0.001) and progression (HR 4.28, p=0.009). Median follow-up was 28.4 months (mo). The median time to visceral involvement from diagnosis was approximately 1 year. Nearly all patients (96.2%) received treatments after vCTCL diagnosis. Median time to first treatment of vCTCL was 2.3mo. Median number of systemic therapies after vCTCL diagnosis was 2. Two patients had complete response (7.7%) and one had partial response (3.8%) with the rest having progressive disease (88.5%). There was no difference in OS or PFS by race, and black patients had a trend toward improved outcomes. Median OS in black and white patients was 18.2mo and 11.4mo respectively (HR 0.5, p = 0.097, Figure 1). Median PFS in black and white patients was 8.7mo and 4.3mo respectively. Black patients had higher median lactate dehydrogenase levels at vCTCL diagnosis (p=0.018) and trended towards an earlier age at diagnosis (54 years vs 62 years) and a shorter time to metastasis (7.9mo vs. 13.3mo) but these factors were not associated with survival outcomes. Most patients received multi-agent chemotherapy (n=13), total electron beam therapy (n=11), and brentuximab vedotin (n=6). Black and white patients had similar time to first treatment and total number of treatments. White patients were more likely to receive combination chemotherapy (66.7% vs 27.3%, p=0.047). Two patients in our cohort had durable complete response to therapy. The first patient developed CNS metastases and achieved durable response with HD-MTX. The second patient had concurrent pulmonary vCTCL and LCT and developed durable response with allogeneic transplantation. Treatments, other demographic information, ECOG, histopathology, LCT were not associated with survival outcomes. Conclusions: Our analysis of a large CTCL cohort from a 30-year period confirms the rarity and poor outcomes in patients with visceral CTCL disease. More prospective studies and clinical trials are needed to guide treatment. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Thalidomide and Sucralfate Reduce Gastrointestinal Bleeding in Adults with Hereditary Hemorrhagic Telangiectasia: The Mexican Experience

Introduction Hereditary hemorrhagic telangiectasia (HHT) is the second most common inherited bleeding disorder, occurring in 1/5,000 to 1/10,000 persons. Has an autosomal dominant transmission and can occur de novo. Telangiectases occurs at characteristics sites: lips, oral cavity, fingers and nose; but visceral lesions are common, affecting gastrointestinal tract (GIT), liver, lung, brain and spinal arteriovenous formations. Nosebleed and GIT can lead to iron deficiency anemia. HHT is an underrecognized disease and delay in diagnose can increase morbidity and mortality as more telangiectases develop with aging. Thalidomide treatment for moderate and severe bleedings, that are defined by requirements of intravenous iron replacement and/or transfusions, has been used since more than a decade with good results (Blood 2021;137:888-895 and Hematology Am Soc Educ Program 2021;1:469-477). Material and methods Anemic adults with HHT based in Curaçao clinical diagnosis criteria, three to four from: a) telangiectases, b) epistaxis, c) visceral involvement and d) direct family history (Am J Med Genet 2009;91:66-67); and positive endoscopic study with moderate to severe GIT bleeding; some patients had a full body CT Scan and showed telangiectasi in al GIT as in Figure 1, the bone window reveal fill blooded telangiectasia. Thalidomide was initiated at 100 mg daily for a month and increased to 200 mg daily if tolerated for 12 months; aspirin 100 mg daily for thrombosis prevention; and omeprazole 20 mg with sucralfate 1 gr twice a day for GIT mucosal protection; transfusion to maintain hemoglobin level at 7-8 g/L and iron carboxymaltose to increase Hb levels and maintain ferritin above 50 ng/mL End points before and after treatment: a) number of episodes of GIT bleeding, b) number of red blood cells transfusions, and c) hemoglobin levels. Results Fifteen patients were included, 9 men and 6 females. Age from 28 to 74 years, median 56. All patients tolerated thalidomide 200 mg daily with minimum side effects and no hematologic toxicity, and completed 12 months period. The number episodes per month of GIT bleeding for all the group before treatment were 28, all patients have at least one monthly episode and two patients more than three; after three months and until end of treatment the number of episodes per month reduced to 5 for all the group. The number of red blood cells transfusion for all the group before treatment were 65 units per month, after three months of treatment reduced to 9 units and at end of treatment to 4 units. The mean of Hb level before treatment were 5.86 g/L, after three months of treatment were 9.2 g/L, and at end of treatment were 11.7 g/L. As a secondary observation the nosebleed episodes were reduced to zero after three months of treatment, from 9 episodes before treatment. No thrombotic complications were observed. Median time to increase the GIT bleeding was 9 months after end of treatment. Discussion In HHT, GIT bleeding is a common symptom in older adults over than 50 years due many factors: nosebleed had received various lines of treatment, ageing of the GIT mucosa that leads to the development of more telangiectases and use of medications for chronic diseases, among others. In this case thalidomide with sucralfate are tolerated and have very good results diminishing the GIT bleeding and the red blood cells transfusions, allowing to increase the Hb levels using IV iron. The response is observed in the three first months of treatment and is maintained until nine months after the end of it. Thalidomide as antiangiogenic and Sucralfate as a local healing substance are useful as an option in this kind of patients in low income countries because Bevacizumab, Pomalidomide and other antiangiogenics are more expensive. More trials using thalidome alone or in combination would help to have strong data in results and improve the quality of life of these patients. Finally, after ellectronic search this is the only Mexican experience in the treatment of HHT. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Profil épidémiologique des toxidermies à Dakar : Etude de 200 cas

Background: Previous studies in Africa have shown severity of toxidermia with a risk of mortality and mucosal synechia. Our objective was to study the epidemiological, clinical, etiological and evolutionary aspects of toxidermia in Dakar. Methods: A cross-sectional retrospective study was conducted at the Department of Dermatology of the Hospital Le Dantec from January 2001 to December 2015. She identified all of the toxidermia cases of hospitalization in this department. The diagnosis was based on the French criteria for drug accountability. Results: Two hundred cases of toxidermia were recorded. The hospital frequency was 9.2%. The sex ratio was 0.61. The average age was 33 years. Clinical forms of bullous toxidermia were Stevens Johnson/Lyell in 54% (n = 108), erythema multiforme in 3% (n = 6), and fixed pigmented erythema in 2% (n = 4). Mucosal involvement was noted in 56.5% (n = 113). Visceral involvement was noted in 15% (n = 30) with respiratory involvement in 24 cases of SSJ/NET and 6 cases of DRESS. The drugs identified were antibiotics in 38,7% (n = 53), analgesics in 15,3% (n = 21), anti-comitials in 13,1% (n = 18), antiretrovirals in 11,7% (n= 16), antituberculosis drugs in 9,5%% (n = 13) and medicinal plants in 11,7% (n = 16). The outcome was favorable in 62.5% (n = 125). Death was noted in 12%. Conclusion: Toxidemia in Dakar are characterized by predominance in severe clinical forms in young adults and mortality was related to infectious and hydro electrolyte complications.

Female Patient with Ceftriaxone-Induced Drug Eruption with Eosinophilia and Systemic Symptoms in Second Level Care. Case Report

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a hypersensitivity reaction. Therefore, the case of a 51-year-old woman with no history of drug allergies is presented. In empirical treatment with Ceftriaxone, presenting 15 days later pruritic maculopapular rash on the chest, abdomen and extremities accompanied by temperature rises of up to 39°C. Laboratories with leukocytes of 47.38/uL, with eosinophils of 27.07/uL, and skin biopsy report with inflammatory infiltrate in the dermis at the expense of eosinophils. regiSCAR and J-SCAR with results of 8 and 6 points respectively. Administering methylprednisolone 250 mg every 24 hours for 3 days, continuing with prednisone 50 mg per day. Improvement of skin lesions and laboratory abnormalities at 72 hours. DRESS induced by this antibiotic is rare. Appropriate assessment of the indications and diagnostic assumption of side effects is important because the manifestations are potentially reversible.of rash, fever, facial edema, lymphadenopathy, hematologic abnormalities, and visceral involvement.

Infantile Periarteritis Nodosa (About 5 Cases and Review of the Literature)

PAN is an inflammatory and necrotizing vasculitis affecting small and medium caliber arteries of the body, rarely described in children. Its pathophysiology is complex and remains poorly elucidated, involving the deposition of circulating immune complexes in the vascular wall, neutrophil anti-cytoplasmic antibodies, the role of cytotoxic lymphocytes, cytokines, environmental factors (infections), as well as genetic susceptibility (mutations in ADA 2 and the MEFV gene). There are two main forms: a classic systemic form with visceral involvement (60% of cases) and a cutaneous form with lesions limited to the skin and muscles (30%), which usually evolve less severely. Positive diagnosis is based on the Eular/Printo/Pres criteria. The treatment depends on the form of PAN, and relies essentially on NSAIDs, colchicine, corticotherapy and immunosuppressants: azathioprine and cyclophosphamide. Our work is a retrospective study of 5 cases of PAN, collected at the IV pediatric department and the pediatric rheumatology consultation of the children's hospital of Rabat between 2009 and 2014: The diagnosis was retained on the criteria of Eular/Printo/Pres. The clinical picture was dominated by skin and joint involvement. One of our patients presented an atypical picture of PAN associated with infective endocarditis and large vessel involvement. All of our patients received corticosteroid therapy, and one of our patients benefited́ in addition to colchicine.

Concept of Cutaneous T Cell Lymphoma in Ayurveda Perspective and its Management by Sodhana, Samana and Rasayana: A Review Article

Cutaneous T cell lymphoma (CTCL) are a rare group of diseases caused by uncontrolled proliferation of T cells which belongs to mature T cell lymphoma having indolent nature. Two thirds of the CTCL are comprised of Mycosis Fungoides (MF) and Sezary Syndrome (SS). They are characterized by macules and patches which on later progresses to tumors or nodules with adenopathy and other organ infiltration. If left untreated the risk of developing infection increases with visceral involvement of skin, GI tract, lungs and adrenals. Diagnosis is done by histopathological appearance, cytogenetic analysis, etiology and the functional biology of neoplastic cells. Imaging techniques (MRI and CT) are widely done to assess the staging of disease and other tissue involvement. Radiotherapy, chemotherapy and retinoids have been in use since long time, but possess many side effects. According to Ayurveda, CTCL can be caused by Ahara like Virudha, Agantuja bhavas, Beeja-beejabhaga-beejabhagavayava dushti and Ojas/bala hani. The clinical features can be related with Kushta and in later stage simulates Dhatugata kushta and Granthi-arbuda. The etiopathogenesis of CTCL can be considered as formation of Ama, Agnimandhya, Srothovaigunya, and Balahani. Management will be preventive, curative and palliative with Sodhana, Samana and Rasayana therapies

S3585 Don’t Forget the Gut: A Case of Gastrointestinal Kaposi Sarcoma

Introduction: Kaposi sarcoma (KS) is a low grade vascular tumor associated with Human Herpesvirus-8 (HHV8) infection. The disease course is indolent with manifestations ranging from cutaneous to fulminant, visceral involvement. In the United States, KS is most often seen in those with AIDS and with increased access to highly active antiretroviral therapy (HAART) the incidence has been decreasing. GI tract involvement of KS is uncommon and few have GI symptoms; therefore, gastrointestinal Kaposi sarcoma (GI-KS) remains under-diagnosed. This case describes a patient with cutaneous involvement of KS found to have GI-KS with no GI symptoms. Case Description/Methods: A 49-year-old African American male presented with shortness of breath, non-productive cough and a 60-lb unintentional weight loss over the past year. He was diagnosed with HIV in 1999 and has been intermittently compliant with HAART therapy. In the past two years, he was started on Bictegravir/emtricitabine/tenofovir alafenamide but was non-compliant. He recently noticed the development of bilateral non-painful and non-pruritic lower skin lesions (Figure a). His CD4 count was low at 88 cells/mm3 with an elevated HIV viral load. His lower extremity skin lesion biopsy showed irregular blood vessels lined by atypical endothelial cells with an infiltrating growth pattern consistent with KS. CT chest demonstrated multiple ground glass opacities and bronchoscopy with FNA were negative for any malignancy. CT abdomen/pelvis was unremarkable. EGD and colonoscopy was done to to rule out systemic involvement which demonstrated scattered moderate mucosal changes characterized by erythema, granular nodularity in the gastric body and nodular mucosa in the rectum (Figure b/c). Biopsies demonstrated spindle cell proliferation involving the lamina propria consistent with KS. Discussion: Kaposi sarcoma is an AIDS-defining rare vascular tumor. Current recommendations for endoscopy are reserved for patients suspicious for GI involvement. This patient had poorly controlled HIV with no GI symptoms and was found to have GI-KS during endoscopy. Management of KS differs based on cutaneous versus systemic involvement. HAART therapy is the first line in management of cutaneous KS while HAART therapy and chemotherapy is first line in management for systemic KS. Therefore, undiagnosed GI-KS in patients with cutaneous KS negatively affects morbidity and mortality. Therefore, clinicians should maintain a high suspicion for GI-KS in those with AIDS and/or cutaneous KS.Figure 1.: a. Lower extremity cutaneous lesions Figure b. Gastric lesions Figure c. Rectal lesions.

S2598 Gastric Kaposi Sarcoma Presenting as Acute Upper Gastrointestinal Hemorrhage in a Heart Transplant Patient

Introduction: Kaposi sarcoma (KS), a multifocal neoplasm of lymphatic cells, occurs more often in organ transplant patients, and its pathogenesis is related to use of immunosuppressive (IS) medications. Acute gastrointestinal hemorrhage due to KS is exceedingly rare and has never been reported in a heart transplant patient. We report a case of KS presenting as gastrointestinal hemorrhage in a heart transplant patient whose bleeding resolved with supportive care and treatment of his underlying KS. Case Description/Methods: A 63-year-old man originally from Sudan with a history of non-ischemic cardiomyopathy requiring heart transplant on IS presented with melena and acute anemia. Medical history included cutaneous KS of the right leg diagnosed 1 year following transplant previously treated with paclitaxel and in clinical remission. He was treated with intravenous proton-pump inhibitor and blood transfusions. EGD showed a patch of nodular mucosa on the lesser curvature of the stomach. Pathology of the nodule showed dilated capillaries with spindle cells in the lamina propria, and staining for human herpesvirus-8 (HHV-8) was positive in the spindled cells, supporting a diagnosis of recurrent KS. He had no further bleeding, hemoglobin stabilized, and he was discharged. He was resumed on paclitaxel for recurrent KS after discharge and had no further bleeding (Figure 1). Discussion: We report a case of KS presenting with GI bleeding in a patient on chronic IS following heart transplant. While GI bleeding from KS has been reported in renal transplant recipients, this is the first such report we are aware of in a heart transplant patient. The GI tract is a common site of visceral involvement in KS, and presentation can include vomiting, diarrhea, and occult blood loss. Overt GI bleeding in KS is rare. Endoscopic appearance varies from flat lesions to polypoid or nodular growths, and histopathology shows spindle cells positive for HHV-8. Management of GI bleeding in KS depends on severity, and in less severe cases, the role of endoscopy is to confirm the visceral spread of KS with biopsy. Thereafter, management includes IS reduction and chemotherapy for refractory disease. Though KS is a rare cause of overt GI bleeding, it should be considered in patients with immunodeficiency or on chronic IS, and biopsy for suspicious lesions should be performed to confirm diagnosis.Figure 1.: Lesser curvature gastric nodule.

S2431 A Rare Case of Esophageal Kaposi Sarcoma Causing Dysphagia

Introduction: Kaposi sarcoma (KS) is an angioproliferative disorder(low grade vascular tumor) caused by human herpesvirus-8 in immunocompromised patients. The disease is multifocal, ranging from indolent skin manifestations to extensive visceral involvement. We are describing a rare case of esophageal KS causing dysphagia. Case Description/Methods: A 57-year-old bisexual male with a medical history of hypertension, syphilis and recent diagnosis of HIV (untreated) admitted for hypotension, tachycardia, nausea, vomiting,hemoptysis and dysphagia to soilds. He was noted to have oropharyngeal lesions and biopsy of the lesions were obtained. An EGD performed for evaluation of dysphagia (denied odynophagia) showed circumferential erythema, purplish plaques and friability of the esophagus. Biopsies were obtained from esophagus. Pathology from tongue, gingiva, proximal and distal esophagus returned positive for Kaposi sarcoma with positive staining for HHV-8 and CD31. CD4 count was 31/uL and HSV8 PCR showed 1,000,000 copies. Patient was treated with Bictegravir, emtricitabine and tenofovir alafenamide. Hematology was consulted for potential pulmonary KS and patient was started on liposomal doxorubicin. He developed Ventricular fibrillation and cardiac arrest. He was revived and intubated. Patient improved initially but developed neutropenic fever. Infectious disease treated him with empirical antibiotics and antivirals. Patient further developed Castleman’s disease, respiratory failure, acute kidney failure requiring CRRT, and altered mental status. Despite aggressive measures patient did not survive (Figure). Discussion: AIDS-related KS varies in clinical progression and occurs in 20% of patients with AIDS. The CD4 count will typically be less than 150 cells per cubic millimeter with a high viral load ranging from greater than 10,000 copies per millimeter. Gastrointestinal manifestation is the most common extra-cutaneous site of KS in AIDS-related cases though rarely does it occur without cutaneous involvement. The majority of the patients are asymptomatic, roughly 75%. Symptomatic patients present with nonspecific findings such as abdominal discomfort, cramps, nausea, vomiting, diarrhea, and upper or lower GI bleed. KS lesions causing dysphagia are extremely rare. The mainstay of therapy is combined antiretroviral therapy (ART). Local intralesional chemotherapy can be utilized to manage limited lesions. Systemic therapy with liposomal anthracyclines is recommended for patients with advanced or rapidly progressive disease.Figure 1.: Kaposi Sarcoma Lesions.

Therapeutic options in refractory anti-MDA5 dermatomyositis triggered by SARS-CoV-2 infection

Anti-MDA-5 dermatomyositis (DM) is a rare disease subtype characterized by rapidly progressive interstitial lung disease alongside skin, vascular and visceral involvement. The severity of the pulmonary disease is corelated with a weaker prognosis. A 31-year-old female patient was admitted for hand arthritis, upper girdle pain and multiple erythematous papular facial lesions on the face, digital ulcerations and Raynaud’s. The symptoms started immediately after the onset of the SARSCoV-2 infection. Positive anti-MDA5 and anti-centromere antibodies were identified, thus amyopathic DM - CREST syndrome overlap diagnosis was placed. Due to pulmonary involvement, corticosteroids, immunomodulatory drugs (mycophenolate mofetil, hydroxychloroquine, cyclophosphamide) were initiated, with no clinical benefits. Lack of response led to initiation of rituximab, oral tacrolimus and nintedanib with no apparent progression of the disease. Refractory cases require escalation of the standard therapeutic approach. SARS-CoV-2 infection can represent a trigger of autoimmunity in DM which needs to be further assessed.

Congenital Cutis laxa: Two pediatric cases

The Cutis laxa syndrome is a group of rare heterogeneous disorders of the elastic tissue characterized mainly by wrinkled, loose skin giving an aged appearance, which may be associated with skeletal abnormalities, developmental abnormalities, and even severe systemic involvement. Cutis laxa syndrome (CL) is either acquired or congenital. There are several forms of congenital cutis laxa distinguished according to the mode of transmission, the extent of visceral involvement, associated anomalies, and the severity of the disease: autosomal dominant CL, autosomal recessive CL, X-linked CL. In the light of data from the medical literature and through the observation of 2 sisters followed up in a pediatric dysmorphology consultation for congenital cutis laxa, the authors underline the clinical, paraclinical, etiogenotypic, therapeutic, and evolutionary peculiarities of this rare disease.

Influence of MRI-based boundary conditions on type B aortic dissection simulations in false lumen with or without abdominal aorta involvement.

Most computational hemodynamic studies of aortic dissections rely on idealized or general boundary conditions. However, numerical simulations that ignore the characteristics of the abdominal branch arteries may not be conducive to accurately observing the hemodynamic changes below the branch arteries. In the present study, two men (M-I and M-II) with type B aortic dissection (TBAD) underwent arterial-phase computed tomography angiography and four-dimensional flow magnetic resonance imaging (MRI) before and after thoracic endovascular aortic repair (TEVAR). The finite element method was used to simulate the computational fluid dynamic parameters of TBAD [false lumen (FL) with or without visceral artery involvement] under MRI-specific and three idealized boundary conditions in one cardiac cycle. Compared to the results of zero pressure and outflow boundary conditions, the simulations with MRI boundary conditions were closer to the initial MRI data. The pressure difference between true lumen and FL after TEVAR under the other three boundary conditions was lower than that of the MRI-specific results. The results of the outflow boundary conditions could not characterize the effect of the increased wall pressure near the left renal artery caused by the impact of Tear-1, which raised concerns about the distal organ and limb perfused by FL. After TEVAR, the flow velocity and wall pressure in the FL and the distribution areas of high time average wall shear stress and oscillating shear index were reduced. The difference between the calculation results for different boundary conditions was lower in M-II, wherein FL did not involve the abdominal aorta branches than in M-I. The boundary conditions of the abdominal branch arteries from MRI data might be valuable in elucidating the hemodynamic changes of the descending aorta in TBAD patients before and after treatment, especially those with FL involving the branch arteries.

Flare-up of mucocutaneous leishmaniasis following infliximab discontinuation and antiparasitic therapy in a patient with juvenile idiopathic arthritis.

A 25-year-old patient had been treated for 4 years with infliximab for JIA. He was admitted for nodular and erythematosquamous lesions of the face and ears that had been evolving for 1 year (Fig. 1A). A skin biopsy with PCR allowed the diagnosis of Leishmania infantum mucocutaneous leishmaniasis (MCL). There was no visceral involvement. The patient lived in the south of France and had not travelled to another endemic area. Infliximab was discontinued and, 10 weeks after the last infusion, treatment with liposomal amphotericin-B 18 mg/kg was initiated. On the third day of treatment, he had a sudden but transient worsening of the lesions (Fig. 1B). One month later, he had complete response to the disease and infliximab was reintroduced (Fig. 1C). No recurrence occurred at a 6-month follow-up. TNFα mediates immune control of Leishmania infection but is also responsible for induced tissue damage. About 50 cases of MCL/cutaneous leishmaniasis have been reported in patients with anti-TNFα in the Mediterranean basin [1]. We report the first case of paradoxical worsening of MCL, which could be explained in two ways: immune restoration following anti-TNFα discontinuation, leading to inflammatory tissue destruction, as has been described in HIV-infected patients with leishmaniasis after highly active antiretroviral therapy (HAART) introduction [2]; and/or a ‘pseudo-Herxheimer’ type reaction related to Leishmania lysis.

Drug rash with eosinophilia and systemic symptoms syndrome masquerading as a lymphoproliferative disorder in a young adult on immunosuppressive therapy for rheumatoid arthritis: a case report

BackgroundThis case reveals a novel presentation of drug rash with eosinophilia and systemic symptoms syndrome that mimics a lymphoproliferative disorder. The heterogeneous clinical presentation of drug rash with eosinophilia and systemic symptoms syndrome gives rise to a broad differential diagnosis that includes a multitude of infectious, inflammatory, and autoimmune conditions. This patient was diagnosed with drug rash with eosinophilia and systemic symptoms syndrome 4 weeks after starting sulfasalazine and 5 weeks after starting hydroxychloroquine for rheumatoid arthritis. Both of these medications have been shown to cause drug rash with eosinophilia and systemic symptoms syndrome, albeit more rarely in the context of hydroxychloroquine. This patient’s history, physical examination, and workup illuminate a case of drug rash with eosinophilia and systemic symptoms syndrome that masquerades as a lymphoproliferative disorder despite its adherence to the RegiSCAR criteria.Case presentationA 22-year-old African-American female with an atopic history and rheumatoid arthritis presented for evaluation of a rash, unremitting fevers, and syncope. She was found to have drug rash with eosinophilia and systemic symptoms syndrome. A syncope workup was unremarkable. Computed tomography of the chest/abdomen/pelvis confirmed extensive lymphadenopathy and revealed a small right pleural effusion (Fig. 5). These imaging findings accompanied by fevers and a rash in the setting of eosinophilia, leukocytosis, and transaminitis led to the clinical suspicion for drug rash with eosinophilia and systemic symptoms syndrome. Steroids were subsequently initiated. Broad-spectrum antibiotic therapy was implemented to cover for possible skin/soft tissue infection due to initial paradoxical worsening after discontinuation of the culprit drugs. Lymph node biopsy ruled out a lymphoproliferative disorder and instead demonstrated necrotizing lymphadenitis. An extensive infectious and autoimmune workup was noncontributory. Clinical improvement was visualized, antibiotics were discontinued, and she was discharged on a steroid taper.ConclusionThis case reflects how drug rash with eosinophilia and systemic symptoms syndrome can masquerade as a lymphoproliferative disorder. Additionally, it highlights the extent to which rapid identification and treatment optimized the patient’s outcome. It calls into question how immunogenetics may factor into a patient’s susceptibility to acquire drug rash with eosinophilia and systemic symptoms syndrome. This case is unique because of the early onset of visceral organ involvement, the type of internal organ involvement, the hematopoietic features, and the lymphadenopathy associated with a disease-modifying antirheumatic drug.