Impact of COVID-19 Pandemic on Clinical Care of Patients and Psychosocial Health of Affected Families with Chronic Granulomatous Disease: an Observational Study from North India.

Day-to-day clinical management of patients with inborn errors of immunity, including chronic granulomatous disease (CGD), has been affected by the coronavirus disease-2019 (COVID-19) pandemic. There is a dearth of information on impact of this pandemic on clinical care of children with CGD and psychological profile of the caretakers. Among the 101 patients with CGD followed up in our center, 5 children developed infection/complications associated with COVID-19. Four of these children had a mild clinical course, while 1 child developed features of multisystem inflammatory syndrome in children (MISC) requiring intravenous glucocorticoids. Parents and caretakers of CGD patients (n = 21) and 21 healthy adults with similar ages and genders were also evaluated on the following scales and questionnaires: COVID-19 Fear Scale (FCV 19S), Impact of Event Scale (IES-R), Depression, Anxiety, and Stress Scale (DASS 21), Preventive COVID-19 Behavior Scale (PCV 19BS), and a "COVID-19 Psychological wellbeing questionnaire." Median age of the parents/caregivers was 41.76 years (range: 28-60 years). Male:female ratio was 2:1. In the study group, 71.4% had higher IES scores compared to 14.3% in controls. The caregivers had a high prevalence of stress, anxiety, avoidance behavior, and depression compared to controls (p < 0.001). Children with CGD have had predominantly mild infection with COVID-19; however, caregivers/parents of these children were at risk of developing psychological distress. The COVID-19 pandemic has brought to light the importance of patients' and caretakers' mental health which needs periodic assessment and appropriate interventions.

A Unique Case of Acute Respiratory Distress Syndrome Secondary to Rheumatoid Lung Disease With Administration of Anti-Tumor Necrosis Factor Alpha (TNFα) Agent.

Patients with rheumatoid arthritis (RA) may experience complications directly from the disease process or from immune-modulating agents used to treat RA. Adalimumab is a recombinant human monoclonal antibody directed against tumor necrosis factor alpha (TNFα) which has been increasingly used in the management of inflammatory and autoimmune diseases. Acute lung injury has been associated with the use of anti-TNFα agents, but the association with adalimumab is rare. Here we present a case of a patient with RA-associated lung disease who developed acute respiratory distress syndrome while being treated with adalimumab. Adalimumab-related lung injury is less common than lung injury associated with other anti-TNFα drugs, thus clinicians should be aware of this condition, as prompt recognition and supportive management can help prevent worsening outcomes.

Granulomatous Hepatitis as Primary Manifestation of Disseminated Histoplasmosis in an Immunocompetent Host Diagnosed on EUS FNA and Liver Biopsy

Introduction: Disseminated histoplasmosis (DH) presents as primarily lung manifestations with extrapulmonary involvement in immunocompromised hosts. Granulomatous hepatitis as first presentation of DH in an immunocompetent host is uncommon. Case Description/Methods: 25-year-old female presented with one month of fever, fatigue, myalgias, 30-pound weight loss, cough, nausea, vomiting, and epigastric pain. She has lived in the Midwest and southwestern US. Presenting labs: TB 1.9 mg/dL, AP 161 U/L, AST 172 U/L, ALT 463 U/L. Workup was negative for COVID, viral/autoimmune hepatitis, sarcoidosis, tuberculosis, and HIV. CT scan showed suspected gallstones and 9 mm left lower lobe noncalcified nodule. EUS showed a normal common bile duct, gallbladder sludge and enlarged porta hepatis lymph nodes which underwent fine needle aspiration (FNA). She was diagnosed with biliary colic and underwent cholecystectomy, with white plaques noted on the liver surface (A). Liver biopsy/FNA showed necrotizing granulomas (B) and fungal yeast on GMS stain (C). Although histoplasmosis urine and blood antigens were negative, histoplasmosis complement fixation was >1:256. She could not tolerate itraconazole for DH, requiring amphotericin B. She then transitioned to voriconazole, discontinued after 5 weeks due to increasing AP. However, her symptoms resolved with normal transaminases. At one year follow up, she is asymptomatic with normal liver function tests. Discussion(s): DH is a systemic granulomatous disease caused by Histoplasma capsulatum endemic to Ohio, Mississippi River Valley, and southeastern US. DH more commonly affects immunocompromised hosts with AIDS, immunosuppressants, and organ transplant. Gastrointestinal involvement is common in DH (70-90%) with liver involvement in 90%. However, granulomatous hepatitis as primary manifestation of DH is rare (4% of liver biopsies). Hepatic granulomas are seen in < 20%. Patients may present with nonspecific systemic symptoms. Serum/urine antigens may be negative. Gold standard for diagnosis is identifying yeast on tissue stains. Recommended treatment is amphotericin B followed by 1 year of itraconazole. However, shorter treatment duration may be effective in immunocompetent hosts. This case is unique in that granulomatous hepatitis was the first presentation of DH in our immunocompetent patient diagnosed on EUS FNA and liver biopsy. Clinicians must have a high degree of suspicion for DH in patients with fever of unknown origin especially in endemic areas regardless of immunologic status. (Table Presented).

Pulmonary sarcoidosis

The lung is the most common organ affected by sarcoidosis. Multiple tools are available to assist clinicians in assessing lung disease activity and in excluding alternative causes of respiratory symptoms. Improving outcomes in pulmonary sarcoidosis should focus on preventing disease progression and disability, and preserving quality of life, in addition to timely identification and management of complications like fibrotic pulmonary sarcoidosis. While steroids continue to be first-line therapy, other therapies with fewer long-term side-effects are available and should be considered in certain circumstances. Knowledge of common clinical features of pulmonary sarcoidosis and specific pulmonary sarcoidosis phenotypes is important for identifying patients who are more likely to benefit from treatment.Copyright © ERS 2022.

Histomorphological Spectrum of Lung Lesions at Autopsy-A Tertiary Care Centre Experience

Background and aims: A wide variety of pathological conditions involve the lungs. In autopsy, the lungs are examined for disease, injury and other findings suggesting cause of death or related changes.Aims & Objectives: The present study aimed to study the histomorphological spectrum of lung lesions at autopsy and to assess the frequency of different types of lesions;and to associate histomorphological changes with cause of death.Material and Methods: It was a one-year observational study conducted in the Department of Pathology, Govt. Medical College, Jammu. Lung tissue pieces from all medicolegal autopsies received were fixed, examined grossly, processed;paraffin embedded sections obtained were stained with Hematoxylin and Eosin stain and examined under microscope. Findings were recorded and tabulated. Result(s): Out of 264 cases, males were predominantly affected (84%);median age was 38 years. The various changes observed were congestion (68%), edema (45.4%), pneumonia (5%), granulomatous inflammation (3%), diffuse alveolar damage (1.5%), haemorrhage (14.4%), interstitial changes (60%), malaria (0.4%) and malignancy (0.4%). Natural deaths were the commonest cause (75, 28%) followed by asphyxial deaths (65, 24.6%). Conclusion(s): Histopathological examination of lung autopsies highlights many incidental findings, establishes underlying cause of death, serves as a learning tool and also holds scope for detection of newer diseases.Copyright © 2023 JK Science.

Outside The Box But All Squeezed In: A 23- year-old Man With Progressive Dyspnea After Overseas Travel

Case Presentation: A 23-year-old previously healthy man presented with progressive dyspnea. Physical examination revealed jugular venous distension and lower extremity edema. Laboratory testing demonstrated elevated B-type natriuretic peptide (193 pg/mL) and normal high sensitivity troponin. Echocardiogram revealed small pericardial effusion, respiratory variation in diastolic flow across the mitral valve, diastolic septal bounce, and annulus reversus (Figure). The differential diagnosis for constrictive pericarditis was broadly considered in the context of a recent febrile illness and frequent travel to Hawaii and Vietnam;we included infectious, autoimmune, and malignant etiologies. Cardiac magnetic resonance imaging revealed thickening and diffuse enhancement in the pericardium as well as ventricular interdependence. Chest CT identified hilar and anterior mediastinal lymphadenopathy. Laboratory testing was positive for QuantiFERON gold and negative for COVID-19, HIV, and ANA. Transbronchial biopsy demonstrated non-necrotizing granulomas with negative acid-fast bacilli smear, culture, and polymerase chain reaction for mycobacterial DNA. Reexamination identified a red-brown plaque on the patient's thigh;biopsy showed granulomatous inflammation and rod-shaped organism with positive FITE staining. A presumed unifying diagnosis was made of extrapulmonary tuberculosis (TB) complicated by constrictive pericarditis. Discussion(s): Despite being a primarily pulmonary disease, systemic involvement can occur with TB with the heart being one of the most common extrapulmonary sites. This case highlights 1) the utility of extra-cardiac diagnostic testing (e.g., dermatologic biopsy) in the diagnosis of constrictive pericarditis, and 2) the diagnostic challenge associated with extrapulmonary TB, particularly paucibacillary disease that requires a detailed social history with "out-of-the-box" thinking.

TCR Alpha Beta and CD19+ Depleted Haploidentical Peripheral Stem Cell Transplantation Using Reduced Toxicity Conditioning Regimen with Pharmacokinetics Guided Busulfan, Fludarabine, Thiotepa and Thymoglobulin Offers Durable Donor Engraftment in Children with Primary Immune Deficiency Disorders

Background: Allogeneic hematopoietic cell transplantation (HCT) with ex vivo T cell receptor (TCR) alphabeta+ T cell and CD19+ B cell depletion is an effective approach for children with primary immune deficiency disorders (PIDD) as it combines advantages of high CD34+ cell dose facilitating rapid engraftment with low risk of Graft Versus Host Disease (GVHD). The ideal pre-conditioning regimen that facilitates robust donor engraftment without increasing risk of transplant related mortality has not been well defined with this approach. Method(s): We report the outcomes of 4 pediatric subjects: Chronic Granulomatous Disease (CGD) (2), Wiskott Aldrich Syndrome (WAS) (1), and RAC2 deficient Severe Combined Immunodeficiency (1) who underwent haploidentical HCT with TCRalphabeta+ T cell/CD19+ depletion at Johns Hopkins All Children's Hospital/Moffitt Cancer Center from 2020-2022 (NCT04414046). Pre-conditioning regimen consisted of distal thymoglobulin (7.5 mg/kg), fludarabine (175 mg/m2), thiotepa (10 mg/kg) and pharmacokinetic guided busulfan targeting a cumulative area under curve (cAUC) (65-75 mgxhr/L). Rituximab (200 mg/m2) was administered on day +1. Result(s): The median age at HCT was 51 months (range 10-163 months). All patients received mobilized peripheral blood stem cells from HLA- haploidentical donors (paternal=1, maternal=1 sibling=2). Median busulfan cAUC for all patients was 69 mgxhr/L (range 65-76). Median CD34 and TCR alphabeta T cell dose was 9.13x106 cells/kg (range 7.0-18.9x106) and 0.7x105 cells/kg (range 0.09-1.0x105). Median times to neutrophil and platelet engraftment were 11 days (9-12) and 11 days (range 8-15), respectively. All 4 patients are alive with median follow-up of 19.5 months (range 7-24). One patient developed late VOD without organ dysfunction that resolved with defibrotide. At last follow up, peripheral T and myeloid chimerisms exceeded 90% in all 4 patients. Average time to CD4 recovery (> 200x106/L) was 142 days. Pre-existing inflammatory bowel disease in CGD (n=1) and WAS (n=1) patients resolved immediately following transplant. There was no graft failure, and none developed Grade III-IV acute or extensive chronic GVHD. Patient with WAS developed recurrent autoimmune cytopenias requiring corticosteroids, rituximab, sirolimus and daratumumab, and ultimately resolved. Viral reactivations included EBV (n= 1), adeno (n= 1), HHV6 (n= 2), BK (n=1), norovirus (n=1), and late HSV (n=1), all responded to antivirals without disease. All patients acquired SARS-Cov-2 after transplant and recovered without sequelae. Conclusion(s): TCR alphabeta+ and CD19+ depleted haploidentical transplantation using a reduced toxicity conditioning regimen with pharmacokinetic guided busulfan, fludarabine, thiotepa and thymoglobulin is well-tolerated in young children with PIDD that results in rapid, durable engraftment with low likelihood of GVHD and graft rejection.Copyright © 2023 American Society for Transplantation and Cellular Therapy

'Granulomatosis with polyangiitis after Pfizer vaccination': a case report.

The advent of COVID-19, caused by the SARS-CoV-2 virus, has resulted in over 541 million cases with 6.32 million deaths worldwide as of June 2022. The devastating consequences of this global pandemic resulted in the expedited generation of mRNA-based vaccines such as the Pfizer-BioNTech and Moderna vaccines. Although the vaccines have been effective, with recent data indicating greater than 95% effectiveness, rare complications have been reported, including manifestations of autoimmune phenomena. Herein, we report a rare case of Granulomatosis with polyangiitis (GPA) in an active duty military male soon after receiving the first dose of the Pfizer-BioNTech COVID-19 vaccine.

A 27-year-old active duty marine was admitted to our hospital after being transferred from Hawaii with concern of new autoimmune disease after receiving the Pfizer vaccine. The patient initially presented to the emergency department with joint pain, fever, chest pain, hemoptysis, and a nose bleed. A comprehensive workup demonstrated elevated inflammatory markers, progressive renal dysfunction, and a positive antibody panel consistent with antineutrophil cytoplasmic antibodies (ANCA) vasculitis. Due to the limited capabilities in his deployed setting, he was transferred to our hospital for a higher level of care. We performed some additional tests to include computed tomography (CT) imaging of his lungs and a renal biopsy which came back consistent with GPA. The patient was started on high-dose prednisone and rituximab, and he achieved remission. He was discharged from the hospital with follow-up arranged with rheumatology and nephrology. He remained in remission on follow-up.

Novel heterozygous PLCG2 variant presenting with very early-onset perianal abscess

Case report Background: Mutations in the PLCG2 gene can cause PLCG2-associated antibody deficiency and immune dysregulation (PLAID) or auto-inflammation with PLCG2-associated antibody deficiency and immune dysregulation (APLAID). PLAID is characterized by urticarial eruptions triggered by evaporative cooling along with cutaneous granulomas. APLAID may present with early-onset skin inflammation and non-infectious granulomas, uveitis, and colitis. Method(s): Case report and literature review. We performed in silico analysis for variants of uncertain significance (VUS). Result(s): A 29-day-old boy presented to emergency department for failure to thrive. He was found to be SARS-CoV2 positive, had an E. coli UTI in the setting of bilateral perinephric masses which subsequently resolved. He also had a perianal soft tissue abscess measuring 4cm in diameter. Mom reported a similar infection when she was age 2. She also reported intermittent diffuse urticaria triggered following perspiration evaporation.Abscess wall histology showed diffuse neutrophil and lymphocytic infiltration, with cultures growing polymicrobial enteric flora. His serum immunoglobulins G, A, M, and E were within reference range. Naive and memory CD4, CD8, CD19 lymphocyte subsets (including NK cells) were also within age-appropriate reference range. He had a normal neutrophil oxidative burst measured using dihydrorhodamine (DHR) flow cytometry following PMA stimulation, which ruled out a diagnosis of chronic granulomatous disease. On evaporative cooling, the patient had a 2mm wheal with surrounding erythema which resolved rapidly with warming. A targeted primary immunodeficiency panel showed a heterozygous VUS in PLCG2, c.688C > G (p.Leu230Val). The variant was absent from major databases and had a calculated CADD score of 17.77. He had symptomatic resolution after completing 3 weeks of ceftriaxone and metronidazole antimicrobials. Given the concern for PLCG2-associated very early-onset inflammatory bowel disease (VEO-IBD), a fecal calprotectin was obtained at 3 months and found to be elevated (157 mcg/g [ < = 49 mcg/g]). However, he had no symptomatic or macroscopic evidence for VEO-IBD. Conclusion(s): Presence of very early onset abscesses has not been previously described in patients with heterozygous PLCG2 deficiency. This case adds to the expanding variable phenotype of PLCG-2-associated immune dysregulation.

Idiopathic Granulomatous Mastitis as an Unusual Cause of Erythema Nodosum in a Malagasy Woman.

Introduction: Idiopathic granulomatous mastitis (IGM) is a rare chronic inflammatory disease. Neoplastic and infectious etiologies must be ruled out. IGM is a diagnostic challenge for countries with high tuberculosis endemicity like Madagascar since it may clinically and radiologically mimic breast tuberculosis. We report a case of IGM associated with erythema nodosum in a Malagasy. Case Report: A 29-year-old primiparous woman came to a dermatological consultation for typical erythema nodosum lesions that appeared one month after a breast swelling. She had no particular medical history. Examination revealed typical erythema nodosum lesions on the legs, voluminous tender mass in the right breast. Bacteriological samples and tuberculosis test were negative. Imaging showed mastitis on the right breast with no evidence of malignancy. Histology revealed a non-caseating granulomas on the lobule of the right breast. As part of an etiological work-up, COVID-19 serology was performed with a positive IgG antibody. The diagnosis of IGM associated with erythema nodosum was evocated. The evolution was favorable under systemic corticosteroid therapy. Discussion: The cause of this uncommon lesion remains obscure. The extramammary localizations such as erythema nodosum and arthralgia suggest an autoimmune origin. This pathogenesis is also reinforced by a good response to systemic immunosuppression. In our patient, the etiological assessment of the mastitis revealed a chronic infection with SARS-CoV-2. Histopathology is the gold standard for the IGM diagnosis which demonstrates a lobulocentric granulomas without caseous necrosis. Oral corticosteroid therapy is the initial choice of treatment. Conclusion: Now, with several cases of concomitant IGM and EN reported, dermatologists should be aware that erythema nodosum can be one of the presenting signs of IGM, since the two conditions appear to be associated. The particularity of our case lies in the incidental discovery of SARS-CoV-2 infection. Is a chronic granulomatous disease associated with SARS-CoV-2 infection, a coincidence?

Granulomatous anterior uveitis following mRNA-based COVID-19 vaccination: A case report.

A 23-year-old patient presented with complaints of redness, pain, photophobia, and blurred vision in the right eye 15 days after she received the third dose of BNT162b2 vaccination. Ocular examination revealed 2+ cellular reactions in the anterior chamber and mutton fat keratic precipitate with no vitritis or retinal alterations. Active uveitis findings regressed with corticosteroid and cycloplegic eye drops. We present a case of unilateral granulomatous anterior uveitis following the BNT162b2 vaccination, with no etiologic factor in uveitis work-up and no previous history of uveitis before vaccination. This report demonstrates a potential causal association of coronavirus disease 2019 (COVID-19) vaccine with granulomatous anterior uveitis.

Sarcoid-like Uveitis with or without Tubulointerstitial Nephritis during COVID-19.

PURPOSE: To report sarcoid-like uveitis with or without tubulointerstitial nephritis (TIN) during coronavirus disease 2019 (COVID-19) and to discuss diagnostic evaluation and treatment. METHODS: Detailed information on the subject's demographics, medical history, ophthalmic examination findings, and laboratory results were obtained from medical records. Fluorescein angiography (FA) and indocyanine green angiography (ICGA) images were evaluated. RESULTS: All seven patients aged between 8 and 17 had bilateral granulomatous panuveitis. TIN preceded in four patients. Thorax computed tomography of patient 1 was found to be compatible with COVID-19, patients 2 and 3 were in contact with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive parents, patients 4 and 5 were found to be SARS-CoV-2 PCR positive, and patients 6 and 7 were positive for SARS-CoV-2 IgG antibodies. ICGA revealed hypofluorescent dots in six patients. Intraocular inflammation was controlled with corticosteroid and/or immunomodulatory therapy. Visual acuity was maintained or improved in all. CONCLUSION: SARS-CoV-2 infection may be related to sarcoid-like uveitis and acute tubulointerstitial nephritis.

An Unusual Case of Systemic Lymphadenopathy - Kimura's Disease.

Background: Kimura's disease (KD) is a rare, chronic inflammatory disease. Clinically, subcutaneous nodules of the head and neck are typical manifestations, often accompanied by local lymphadenopathy or salivary gland enlargement, but there is also systemic damage, such as kidney involvement. Due to the lack of specific markers and imaging examination is not specific, it is difficult to clinically diagnose accurately and can be easy to misdiagnose. The treatment of KD is still not standardized and overtreatment can affect the quality of life. Case Presentation: The case of a 26-year-old man complaining of chest pain with self-conscious progressive lymphadenopathy after receiving Pfizer BioNTech COVID-19 vaccine for more than 1 month is presented. Eosinophil levels were normal and IgE elevated and the final diagnosis of KD was eventually confirmed by lymph node biopsy, which revealed lymphadenopathy with extensive eosinophilic infiltration in the right neck. Treatment was prednisone combined with methotrexate, resulting in satisfactory control. Conclusion: This case demonstrates that that Kimura disease can involve systemic lymphadenopathy, not only in the head and face or regional lymphadenopathy, suggested that KD should be excluded in patients with systemic lymphadenopathy. The current patient's response to treatment suggested that corticosteroid combined with disease-modifying antirheumatic drugs (DENARDs) was a promising treatment for KD patients with systemic damage. It is worth noting that the mechanism of immunity in the pathogenesis of KD still needs to be further studied.

Tsukamurella and mycobacterium tuberculosis pneumonia co-infection

Case Report: Tsukamurella species are aerobic, partially acid fast saprophytes commonly isolated from soil and water. They are opportunistic pathogens known to infect multiple organs and can contribute to significant pathologies such as bacteremia, peritonitis, and respiratory tract infections. Moreover, Tsukamurella shares certain characteristic properties to Mycobacterium tuberculosis and Actinomyces species, including the acid fast stain, which can contribute to misdiagnosis of patients. A 68 year old female patient presented to the ED for shortness of breath, fatigue, and weight loss for 6 months. The patient's past medical history includes pulmonary fibrosis, type 2 diabetes, coronary artery disease with stent, hyperlipidemia, hypertension, and M. tuberculosis infection when she was 3 years old in Finland. On admission, labs revealed thrombocytosis (reactive 555 000/microL), leukocytosis (14 450/microL), and microcytic anemia (9.4 microg/dl). Moreover, C reactive protein was elevated and procalcitonin was normal (0.06 microg/l);a COVID-19 PCR was negative. An X-ray revealed severe patchy and interstitial infiltrates throughout both lungs with parenchymal scarring and pleural thickening in the periphery of the left mid-lung zone with multifocal pneumonia. Blood and sputum cultures were performed under the impression of pneumonia, and treatment with azithromycin and ceftriaxone was started. A M. tuberculosis infection was suspected due to a positive AFS. Further chest CT suggested multifocal pneumonia within the left lung in addition to apparent cavitary lesions versus bulla, a chronic interstitial lung disease with traction bronchiectasis, calcified right lower lung nodule, and calcified hilar lymph nodes suggesting a history of granulomatosis diseases. A bronchoscopy with Bronchoalveolar lavage was performed. The initial sputum specimen direct smear showed acid-fast stain positive with Actinomyces growth, and Penicillin G was added to the treatment. Samples were sent to the state department lab, and biopsy revealed granulomatous inflammation negative for malignant cells. One month later, the patient's sputum culture showed Tsukamurella for High-performance liquid chromatography (HPLC). Moreover, a rifampicin sensible M. tuberculosis complex by NAA was also positive six weeks later. The patient was started on a complete TB regimen and continued in the outpatient pulmonology clinic with the addition of levofloxacin for three months and rifampicin substituted for rifabutin. As demonstrated in the case above, a Tsukamurella infection can present similarly to a Mycobacterium infection. Patients may be misdiagnosed or potentially be co-infected. Our patient was further tested and appropriately treated for Tsukamurella after further extensive diagnostic screenings. Due to a high rate of missed cases, it is important to keep Tsukamurella infection on the differential diagnosis as the patient presentation may initially appear to be a Mycobacterium or other pulmonary infection. Copyright © 2023 Southern Society for Clinical Investigation.

Granulomatous cheilitis in a patient after SARS-CoV-2 infection treated with antibiotics: a case report

Granulomatous cheilitis or Miescher's cheilitis is a rare granulomatous disorder defined by recurrent lip swelling or edema of other facial soft tissues. Histopathology shows non-caseous granulomas and multinucleated giant cells. The exact etiology is unknown, although genetic background, immunological irregularities, and systemic or infectious diseases contribute to the onset of disease. There are no treatment guidelines. The usual treatment options include systemic or intralesional corticosteroids, a spectrum of antibiotics, and immunosuppressants. A 63-year-old patient presenting with lip swelling and simultaneous swelling of other facial soft tissues was diagnosed with granulomatous cheilitis. The symptoms occurred 3 weeks after SARS-CoV-2 infection. Initial treatment with systemic corticosteroids and antihistamines was inadequate. Here we report successful treatment with a combination of doxycycline and metronidazole. Copyright © 2022, Slovene Medical Society. All rights reserved.

Unmasking sarcoidosis following SARS-CoV-2 vaccination: A case report.

Sarcoidosis is an inflammatory and granulomatous disorder, developed due to dysregulation between immune response and certain environmental antigens. We hereby report an interesting case of sarcoidosis following COVID-19 vaccination (COVIran Barekat), which presented with inflammation of previous tattoo sites as well as the development of erythema nodosum and systemic lymphadenopathy, suggested a possible link between the COVID vaccination and dysregulation of the inflammatory process and served as a reminder for clinicians to have enough vigilance before proposing a vaccine booster to these patients.

The Multiple Faces of Nitric Oxide in Chronic Granulomatous Disease: A Comprehensive Update.

Nitric oxide (NO), a signaling molecule, regulates multiple biological functions, including a variety of physiological and pathological processes. In this regard, NO participates in cutaneous inflammations, modulation of mitochondrial functions, vascular diseases, COVID-19, neurologic diseases, and obesity. It also mediates changes in the skeletal muscle function. Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder characterized by the malfunction of phagocytes caused by mutations in some of the genes encoding subunits of the superoxide-generating phagocyte NADPH (NOX). The literature consulted shows that there is a relationship between the production of NO and the NADPH oxidase system, which regulates the persistence of NO in the medium. Nevertheless, the underlying mechanisms of the effects of NO on CGD remain unknown. In this paper, we briefly review the regulatory role of NO in CGD and its potential underlying mechanisms.

ATYPICAL VARIANT OF GRANULOMATOSIS WITH POLYANGIITIS WITH EOSINOPHILIA

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 a necrotizing granulomatous vasculitis affecting small-to-medium sized blood vessels. GPA is highly associated with antineutrophil cytoplasmic antibodies (ANCAs) and often triggered by environmental factors such as medications and infectious agents. Tracheobronchial stenosis and diffuse alveolar hemorrhage are serious complications of GPA. CASE PRESENTATION: A 35-year-old Caucasian male with a history of chronic sinusitis requiring balloon sinuplasty and recent tympanostomy had presented multiple times to the emergency room due to dyspnea and cough with pinkish sputum production. This was associated with sore throat and fever, which were attributed to his COVID-19 infection and treated with supportive care. Due to persistent drainage through his tympanostomy he was prescribed levofloxacin by his ENT specialist. After the second dose of levofloxacin, he developed Raynaud's phenomenon, diffuse purpuric lesions and swelling over his lower extremity, eyelids, and elbows. Four days later he developed worsening hemoptysis and dyspnea for which he was admitted for further evaluation. Laboratory findings were remarkable for peripheral eosinophilia, elevated ESR 19mm/hr, CRP 9.2mg/dl, c-ANCA 1:320 titer, positive proteinase-3 antibodies and normal p-ANCA titers. Urinalysis with microscopic hematuria. Chest CT scan showed ground glass opacity, consolidative infiltrate with subpleural sparing and minimal left bronchial stenosis. Bronchoscopy suggestive of diffuse alveolar hemorrhage. Limited lung biopsy showed ulcer and granulation tissue with abundant eosinophils, but no granulomatous inflammation noted. Pulse dose steroids and Rituximab were initiated, and rapid clinical improvement was noted. Patient was discharged on prednisone taper and Pneumocystis jiroveci prophylaxis. DISCUSSION: We believe that GPA may have been triggered by recent COVID-19 infection and levofloxacin use. Mild peripheral blood and tissue eosinophilia (<12%) has been described in GPA, however it is a rare finding. GPA and eosinophilic granulomatosis with polyangiitis (EGPA) are both ANCA vasculitis that involve lungs and kidneys. GPA presents with sinusitis, alveolar hemorrhage and high titers of PR-3 antibodies. EGPA presents with a history of atopic, asthma and high titers of myeloperoxidase-ANCA along with abundant peripheral eosinophils. Our patient best fits the diagnostic criteria for GPA with eosinophilia variant rather than EGPA. Our patient had no history of asthma or atopic disease and p-ANCA was normal, which also points away from EGPA. CONCLUSIONS: Clinicians should recognize the differential diagnosis for eosinophils in ANCA vasculitis. Early diagnosis of ANCA vasculitis and initiation of appropriate treatment is important to decrease morbidity and mortality. Reference #1: Potter MB, Fincher RK, Finger DR. Eosinophilia in Wegener's Granulomatosis. Chest 116: 1480-1483, 1999 Reference #2: Krupsky, Meir et al. Wegener's Granulomatosis With Peripheral Eosinophilia. CHEST, Volume 104, Issue 4, 1290 - 1292 Reference #3: Kitching AR, Anders HJ, et al. ANCA-associated vasculitis. Nat Rev Dis Primers. 2020 Aug 27;6(1):71. doi: 10.1038/s41572-020-0204-y. PMID: 32855422. DISCLOSURES: No relevant relationships by Afoma King No relevant relationships by Joshuam Ruiz Vega No relevant relationships by Krishna Shah no disclosure on file for Milos Tucakovic;

COVID-19-INDUCED PULMONARY SARCOIDOSIS: A CASE REPORT

SESSION TITLE: Unique Inflammatory and Autoimmune Complications of COVID-19 Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Sarcoidosis is a disorder with multisystem involvement of unclear, and likely multifactorial, etiology. A majority of cases (up to 90%) include lung involvement, and hilar/mediastinal lymphadenopathy is frequently seen. Since the beginning of the COVID-19 pandemic, multiple complications of COVID-19 have been reported. We present a case of a female patient who developed new-onset, biopsy-proven Pulmonary Sarcoidosis after having COVID-19 pneumonia. CASE PRESENTATION: A forty-eight-year-old female with a past medical history of hypertension presented to the emergency department with a complaint of fever, shortness of breath, and cough. She was subsequently diagnosed with COVID-19 infection/pneumonia. A computed tomography angiogram of the chest was completed to evaluate an abnormal chest radiograph and to rule out pulmonary embolism and revealed pulmonary nodules throughout both lungs with mediastinal and hilar lymphadenopathy. She was referred to the pulmonary clinic for further evaluation of her abnormal computed tomography scan of the chest and presented after quarantine for her COVID-19 infection. She denied any history of Sarcoidosis and denied any mold exposure. She underwent bronchoscopy, and pathology results were consistent with non-caseating granulomas concerning for Sarcoidosis. Over the course of a few days, her symptoms improved. Repeat computed tomography scan of the chest was completed, which showed complete resolution of the previously identified pulmonary nodules with interval improvement of mediastinal adenopathy. DISCUSSION: With the increased number of COVID-19 cases worldwide, an ever-growing list of pulmonary and extrapulmonary manifestations of COVID-19 have been reported. To our knowledge based on literature review, there have only been a few case reports of COVID-19 induced Sarcoidosis. Although the pathophysiology of Sarcoidosis largely remains unknown, inflammation is mediated through the dysregulation of several different cytokines (1). Behbahani, et al. proposed noncaseating granulomas formation as a sarcoid-like immune reaction to SARS-CoV-2. Ekinci et al. reported type-I IFN and IFN-γ role in triggering granuloma formation (2). In our patient, the biopsy-proven presence of non-caseating granuloma formation and subsequent rapid improvement of radiological lesions on computed tomography scan after recovery from COVID-19 pneumonia supports the diagnosis of COVID-19 induced Sarcoidosis. CONCLUSIONS: With the COVID-19 pandemic ongoing, physicians must be aware of the pulmonary and extrapulmonary manifestations of COVID-19 infection. Further studies are required in order to manage such cases and to evaluate COVID-19 infection as an infectious antigen capable of triggering granulomatous inflammation resulting in Pulmonary Sarcoidosis. Reference #1: Capaccione KM, McGroder C, Garcia CK, Fedyna S, Saqi A, Salvatore MM. COVID-19-induced pulmonary sarcoid: A case report and review of the literature. Clin Imaging. 2022;83:152-158. doi:10.1016/j.clinimag.2021.12.021 Reference #2: Polat Ekinci A, Büyükbabani N, Meşe S, Pehlivan G, Okumuş NG, Ağaçfidan A, Özkaya E. COVID-19-triggered sarcoidal granulomas mimicking scar sarcoidosis. J Eur Acad Dermatol Venereol. 2021 Aug;35(8):e477-e480. doi: 10.1111/jdv.17286. Epub 2021 May 1. PMID: 33871106;PMCID: PMC8250646. DISCLOSURES: No relevant relationships by Zachary Anderson No relevant relationships by Sakina Batool No relevant relationships by Adnan Khan No relevant relationships by Bireera Muzaffar No relevant relationships by Ramsha Zafar