Transplant Graft TMA Injury Post COVID-19 Vaccination

Purpose: Vaccination against SARS-CoV-2 is essential. Complicating this effort are reports of a suboptimal response to the SARS-CoV-2 spike protein in patients on immunosuppressive medications and possible thrombotic microangiopathy (TMA) in renal transplant patients who receive the mRNA type vaccines. Method(s): 48 year old male with end stage renal disease who received a living unrelated transplant in 2015. Pre-operative creatinine was 10.42 mg/dL and decreased to 2.48 mg/dL within a week. Patient received Basiliximab induction and maintained on tacrolimus and mycophenolate (MMF). One month post-transplant patient was diagnosed with TMA. Tacrolimus was stopped and patient was switched to Sirolimus and continued on MMF. Patient was followed closely by transplant nephrology for the next 5 years with a baseline creatinine of 1.9 mg/dL, protein to creatinine ratio below 0.5 mg/mg and well controlled diabetes. No DSA Class I or II detected on regular testing. Patient was compliant with all prescribed medications. On January 25 2021 patient received Pfizer Vaccine. Second Pfizer vaccine administered on February 18 2021. A week later creatinine was noted to be 3.44 mg/dL. Repeat creatinine of 4.27 mg/dL. Biopsy revealed diffuse lymphocytic interstitial inflammation, peritubular capillaritis, and C4D negative. Findings consistent with chronic TMA. DSA testing revealed Class II DSA:DQ2 (SI-5933), Allosure 1.2 %. BK < 500 and CMV undetected. Patient received therapeutic plasma exchange, IV Ig infusion and steroids while on MMF and sirolimus. His creatinine decreased to 2.9 mg/dL on discharge. Over the next 6 months graft function deteriorated. He is now CKD stage 5 and under evaluation for a second transplant. Result(s): There are case reports of COVID-19 vaccine administration and transplant graft dysfunction. A possible mechanism involves the mRNA lipid nanoparticleencapsulated platform producing such a robust CD4 and CD8 T-cell response that pro-inflammatory cytokines are activated or that immune complex associated glomerular disease occurs resulting in the development of TMA in susceptible patients. Conclusion(s): A possible link between SARS CoV-2 vaccination and kidney transplant TMA warrants the implementation of close surveillance of vaccinated transplant patients, particularly susceptible individuals. More research is needed to determine if this link exists.

A CASE OF GRANULOMATOSIS WITH POLYANGIITIS

SESSION TITLE: Critical Systemic Disease Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Granulomatosis with polyangiitis(GPA) is an autoimmune small vessel vasculitis that is included in the group of anti-neutrophilic cytoplasmic antibody(ANCA)- associated small vessel vasculitides (AAVs). GPA is a systemic disease, however acronym ELK is used to describe the most common involvement of Ear, nose, throat, Lungs, and Kidneys. We report a case of GPA, highlighting its presentation. CASE PRESENTATION: 59-year old female presented with vaginal bleeding, malaise, blurry vision, non productive cough and shortness of breath few days after receiving COVID-19 vaccine. Physical exam was remarkable for bilateral conjunctival injection with right sided ptosis and inguinal lymphadenopathy. Laboratory findings were significant for acute kidney injury and anemia. Computed tomography (CT) of chest revealed bilateral bronchovascular nodules and masses with interlobular septal thickening and enlarged mediastinal lymph nodes. Fine needle aspiration of left inguinal lymph node was negative for malignancy. Bronchoscopy with bronchial brush revealed alveolar hemorrhage with capillaritis;bronchoalveolar lavage(BAL) showed hemosiderin laden macrophages. Tissue biopsy was negative for malignancy. Testing for pulmonary renal syndrome was positive for C-ANCA and proteinase-3 (PR-3) antibodies. Anti-GBM antibody and anti-MPO antibody was negative. Plasmapheresis (PLEX) and pulse dose steroids were initiated however the patient was unable to tolerate the treatment. Her clinical condition continued to decline requiring multiple pressors, broad spectrum antibiotics and continuous renal replacement therapy. She was transitioned to comfort care per family's wishes and passed away. DISCUSSION: GPA is a rare necrotizing granulomatous vasculitis of small to medium sized vessels that can affect any organ but mainly involves the upper and lower respiratory tract. Necrotizing glomerulonephritis is common. Pulmonary involvement can include consolidation, tracheal or subglottic stenosis, diffuse alveolar hemorrhage, pleural effusion and interstitial lung disease. Lymphadenopathy, as seen in our patient is a rare presentation. Tissue biopsy is crucial for the diagnosis. Association with PR-3 ANCA is seen in more than 80% of GPA patients. Cases of AAVs after administration of COVID vaccine have been reported in the literature, although it is difficult to demonstrate causal relationship. Treatment of GPA with immunosuppression, usually corticosteroids, rituximab or cyclophosphamide, is recommended. The role of PLEX continues to evolve with emerging data, but use of this therapy is reasonable for patients with severe kidney injury and DAH secondary to active vasculitis refractory to immunosuppressive therapy. CONCLUSIONS: Early diagnosis of GPA is challenging as it can mimic metastatic lung malignancy. It should be considered in a broad range of differentials when evaluating patients presenting with pulmonary nodules. Reference #1: Greco A, Marinelli C, Fusconi M, Macri GF, Gallo A, De Virgilio A, Zambetti G, de Vincentiis M. Clinic manifestations in granulomatosis with polyangiitis. Int J Immunopathol Pharmacol. 2016 Jun;29(2):151-9. doi: 10.1177/0394632015617063. Epub 2015 Dec 18. PMID: 26684637;PMCID: PMC5806708. Reference #2: Kitching, A. R., Anders, H. J., Basu, N., Brouwer, E., Gordon, J., Jayne, D. R., Kullman, J., Lyons, P. A., Merkel, P. A., Savage, C., Specks, U., & Kain, R. (2020). ANCA-associated vasculitis. Nature reviews. Disease primers, 6(1), 71. https://doi.org/10.1038/s41572-020-0204-y Reference #3: Szymanowska-Narloch, A., Gawryluk, D., Błasińska-Przerwa, K., & Siemińska, A. (2019). Atypical manifestations of granulomatosis with polyangiitis: the diagnostic challenge for pulmonologists. Advances in respiratory medicine, 87(6), 244–253. https://doi.org/10.5603/ARM.2019.0062 DISCLOSURES: No relevant relationships by Sean Davidson No relevant relationships by Eric Flenaugh No relevant relationships by Marilyn Foreman No relevant relationships by KOMAL KAUR No relevant relationships by Gabriela Oprea-Ilies

DIFFUSE ALVEOLAR HEMORRHAGE: A NOVEL ETIOLOGY?

SESSION TITLE: Pathologies of the Post-COVID-19 World SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Diffuse Alveolar Hemorrhage (DAH) is a pathological lung condition that can result in rapid respiratory failure and death, with classic cases revolving around autoimmune pathology. However, new information regarding immune dysregulation post- covid infection continues to develop. Here we describe the case of a woman diagnosed with post-covid DAH with no prior autoimmune conditions. CASE PRESENTATION: A 49 y/o female with no history of rheumatologic or connective tissue disease history was evaluated in the ED for worsening acute hypoxic respiratory failure. She reported fever, cough without hemoptysis, and shortness of breath. She was recently discharged 7 days prior on 2L of oxygen after a 10 day ICU stay requiring high flow nasal cannula support for Covid pneumonia. A new chest computed tomography (CT) showed no pulmonary embolus, but revealed increased bilateral interstitial and alveolar opacities. Prednisone 60 mg daily and empiric antimicrobial therapy were initiated, and bacterial/fungal serologies were sent. Further deterioration occurred over 2 days resulting in need for mechanical ventilation. Bronchoscopy with bronchoalveolar lavage (BAL) was performed showing increasing bloody return through each cycle raising concerns for DAH. Extensive infectious workup and connective tissue disease/vasculitis panels were negative except for a positive ANA. A steroid burst with 1 gram of solumedrol daily for 3 days was started followed by prednisone 60mg daily with a 10mg weekly taper. Remarkable clinical improvement was seen and while repeat CT showed worsening infiltrates a repeat bronchoscopy 7 days later showed no residual blood on BAL and she was extubated and rapidly titrated down to room air over 24 hours. DISCUSSION: Diffuse alveolar hemorrhage is a rare life-threatening condition brought on by disruption of the alveolar-capillary basement membrane, and carries a high mortality rate of 46% (1). There are 3 main classifications of DAH, based upon histopathologic pattern, including pulmonary capillaritis (PC), bland pulmonary hemorrhage, and diffuse alveolar damage (DAD), as seen in acute respiratory distress syndrome (2-3). In this case, DAH was likely due to a combination PC and DAD, with the former contributing heavily given her response to pulse steroids. There is much to learn about long covid auto-immune dysregulation. Since DAH mimics pneumonia on CT, in those patients returning to the hospital post-covid infection, DAH should be considered as prompt treatment is required (3). CONCLUSIONS: DAH is a rare disease that can be difficult to recognize. Only a minority of patients present with hemoptysis and CT can be mistaken for worsening multifocal pneumonia. With a wide variety of new post-covid infection syndromes being described, auto-immune dysregulation leading to DAH may represent a small but significant proportion of covid readmissions. Reference #1: Bradna P, Manak J, Soukup T, Toms J, Kodeda M. Ab0565 diffuse alveolar hemorrhage, diagnosis, treatment and 3-year prognosis in a group of 32 cases of tertiary centre. Annals of the Rheumatic Diseases. 2016;75(Suppl 2):1098-1098. Reference #2: Franks TJ, Koss MN. Pulmonary capillaritis. Curr Opin Pulm Med. 2000;6(5):430-435. Reference #3: Lara AR, Schwarz MI. Diffuse alveolar hemorrhage. Chest. 2010;137(5):1164-1171 DISCLOSURES: No relevant relationships by Nicholas Germano No relevant relationships by Bryan Krajicek

Transplant Graft TMA Injury Post COVID-19 Vaccination

Vaccination against SARS-CoV-2 is essential. Complicating this effort are reports of a suboptimal response to the SARS-CoV-2 spike protein in patients on immunosuppressive medications and possible thrombotic microangiopathy (TMA) in renal transplant patients. 48-year-old male who received a living unrelated transplant in 2015. Pre-operative creatinine was 10.42 mg/dL and decreased to 2.48 mg/dL within a week. Patient received Basiliximab induction and maintained on tacrolimus and mycophenolate (MMF). One month post-transplant patient was diagnosed with TMA. Tacrolimus was stopped and patient was switched to Sirolimus and continued on MMF. Patient was followed closely by transplant nephrology for the next 5 years with a baseline creatinine of 1.9 mg/dL, protein to creatinine ratio below 0.5 mg/mg and well controlled diabetes. No DSA Class I or II detected on regular testing. Patient was compliant with all prescribed medications. On January 25 2021 patient received Pfizer Vaccine. Second Pfizer vaccine administered on February 18 2021. A week later creatinine was noted to be 3.44 mg/dL. Repeat creatinine of 4.27 mg/dL. Biopsy revealed diffuse lymphocytic interstitial inflammation, peritubular capillaritis, and C4D negative. Findings consistent with chronic TMA. DSA testing revealed Class II DSA:DQ2 (SI- 5933), Allosure 1.2 %. BK < 500 and CMV undetected. Patient received therapeutic plasma exchange, IV Ig infusion and steroids while on MMF and sirolimus. His creatinine decreased to 2.9 mg/dL on discharge. Over the next 6 months graft function deteriorated. He is now CKD stage 5 and under evaluation for a second transplant. There are case reports of COVID-19 vaccine administration and transplant graft dysfunction. A possible mechanism involves the mRNA lipid nanoparticle-encapsulated platform producing such a robust CD4 and CD8 T-cell response that pro-inflammatory cytokines are activated or that immune complex associated glomerular disease occurs resulting in the development of TMA in susceptible patients. A possible link between SARS CoV-2 vaccination and kidney transplant TMA warrants the implementation of close surveillance of vaccinated transplant patients, particularly susceptible individuals. More research is needed to determine if this link exists.

Isolated pauci-immune pulmonary capillaritis associated with an extensive bilateral hemothorax and pleuro-pericarditis

Introduction: Isolated pauci-immune pulmonary capillaritis (IPIPC) is a rare disorder characterized by small vessel vasculitis limited to alveolar capillaries in the absence of systemic manifestations. There are very few case reports of this disorder in the medical literature. Case Report: A 37-yo male with no known history of autoimmune pathology who was admitted to the hospital for evaluation and treatment of dyspnea and thoracalgia. Peripheral blood cultures, serum studies to detect Legionella and Pneumococcus antigens, and a nasopharyngeal swab test for covid-19 were all negative. Chest imaging revealed bilateral pleural effusions from the base to the apices with concomitant atelectasis of the adjacent lung parenchyma. Although the results of an 18F-PET-CT scan revealed no pathological uptake, video-assisted thoracoscopy revealed diffusely edematous pleura with crater-like patches with new onset of venous vessel varicosities, intra-alveolar hemorrhages associated with disordered vascularization, suggesting small vessel vasculitis. Histologic findings included widespread intra-alveolar hemorrhage with organizing injury, hemosiderin-laden macrophages, scattered intra-arterial thrombi, and diffuse perivascular neutrophilic infiltrates consistent with a diagnosis of capillaritis. Conclusions: Given the negative immune studies (save for a weakly-positive lupus anticoagulant and no evidence for extra-pulmonary vasculitis, the diagnosis was Isolated pauci-immune pulmonary capillaritis. The patient recovered in response to immunosuppressive/anti-inflammatory therapy.

An unusual case of systemic lupus erythematosus with Sjögren syndrome and recurring episodes of macrophage activation syndrome in a boy - difficulties to diagnose, difficulties to treat

Introduction: systemic lupus erythematosus with juvenile onset (jSLE), especially in boys, can occur with unusual manifestations, including Sjogren's syndrome (SS), accompanied by unexpected complications and difficulties in choosing therapy. Objectives: to present a rare case of successfully application of abatacept in an jSLE+SS in a boy who had two episodes of macrophage activation syndrome (MAS). Methods: Case report. Results: 4-year-old boy admitted to our clinic for the first time in 2010 presenting the 6-month history of disease. There were fever up to 39°C, polyarthritis, anemia, trombocytopenia, hyperIgG-emia, increase TA (2N), CRP (20 mg/l), RF 30 mg/l at the disease onset. Initially JIA, polyarthicular sybtype, RF+ was diagnosed in regional hospital. Treatment with NSAIDs, GC iv 125 mg No3, methotrexati 7,5 mg weekly was started. During the next 3 weeks laboratory results were constantly getting worse (HB 80 τ/π, trombocytes 145000, leucocytes 1000, increase TA 10N) and new clinical symptoms occurred (maculopapular rash with itching;splenomegaly;febrile fever). He received GC iv + per os 1 mg/ kg with a short-term effect. On 1st admission in our clinic in September of 2010, he had general fatigue and tiredness, classic malar rash, severe cutaneous vasculitis (palpable purpura and digital capillaritis), Raynaud's syndrome, enanthema, myopathy, lymphadenopathy, hepatosplenomegaly, polyarthritis. Data of laboratory tests: Hb 96g/l, ESR 27 mm/h, ANA titer 1:640 h+sp+cytopl, anti-SS-A(Ro)>200 U/ml, RF 230 ME/ml, C4 0.07 g/l. The revision of bone marrow biopsy showed changes typical for MAS. So jSLE was diagnosed as with SLICC criteria, 2012 with MAS at onset according the preliminary diagnostic criteria for MAS Complicating SLE. The initial SLEDAI was 29. Patient failed to respond to GC iv repeating courses, GC per os max 0.7 mg/kg, IVIG repeating courses, DMARDs consequentially: cyclophosphamide iv, azathioprine, mycophenolate mofetil (MMF) + hydroxychloroquine. Rituximab (RTX) was introduced in November of 2013 due to inefficiency of prior therapy in dose 375mg/m2 weekly N2 on course. Concomitant therapy: GC per os 0.5 mg/kg, MMF 500 mg/day, hydroxychloroquine 200 mg/day. Treatment with RTX allowed to decrease the dose of GC to 0.2 mg/kg, to reduce the activity of the disease (SLEDAI=4), but relapses of the disease required a repeat of RTX therapy every 6 months (5 courses in total). Patient developed a recurrent episode of MAS on 6th years of disease (the 8th day after RTX - 5th course, 1st infusion). Therapy of RTX was discontinued. In June 2016 Sjogren's syndrome has been verified (according to parotid sialography, unstimulated sialometry in combination with clinical signs of dry mouth, anti-SS-A(Ro)+, RF+). Correction of therapy was carried out at the expense of the change a dose of GC, the dose of MMF was increased to 750 mg per day. Patient received repeat courses of IVIG due to recurrent infections of mouth. Since October 2017 flare due to fever, polyarthritis, skin and mucosal lesions. The dose of GC has been increased to 0.5 mg/kg. In November 2017, abatacept therapy with 10 mg/kg was started with good safety. Inactive status of the disease was achieved after 12 months of therapy. Now boy receives abatacept during 42 months, continues GC 5 mg per day, hydroxychloroquine 100 mg per day, MMF 750 mg per day. In November 2020, he underwent COVID-19 with minimal manifestations (runny nose, fatigue, positive PCR test) without reactivation of rheumatic disease. Conclusion: This clinical case demonstrates efficacy and safety of abatacept in the rare combination of jSLE, SS and recurring episodes of MAS in boy with early onset.

The evolution of pulmonary pathology in fatal COVID-19 disease: an autopsy study with clinical correlation.

The pandemia of coronavirus disease 2019 (COVID-19) has caused more than 355,000 confirmed deaths worldwide. However, publications on postmortem findings are scarce. We present the pulmonary findings in four cases of fatal COVID-19 with a spectrum of lung pathology reflecting disease course and duration, invasive therapies, and laboratory features. Early disease is characterized by neutrophilic, exudative capillaritis with microthrombosis and high levels of IL-1beta and IL-6. Later stages are associated with diffuse alveolar damage and ongoing intravascular thrombosis in small to medium-sized pulmonary vessels, occasionally with areas of infarction equivalents, accompanied by laboratory features of disseminated intravascular coagulation. In late stages, organizing pneumonia with extensive intra-alveolar proliferation of fibroblasts and marked metaplasia of alveolar epithelium can be observed. Viral RNA is encountered in the lung, with virus particles in endothelial cells and pneumocytes. In many patients, multi-organ failure with severe liver damage sets in finally, possibly as consequence of an early-onset pro-inflammatory cytokine storm and/or thrombotic microangiopathy.