Azadeh, Natalya

Abstract Autoinflammatory syndromes are increasingly recognized as heterogeneous disorders of innate immune dysregulation, often overlapping in clinical and genetic features. Although pulmonary manifestations are uncommon, several autoinflammatory conditions such as VEXAS syndrome, juvenile rheumatoid arthritis, adult-onset Still’s disease, and Familial Mediterranean Fever can produce inflammatory pulmonary nodules that mimic metastatic malignancy. Recognition of these presentations is critical, as they can respond dramatically to immunosuppressive therapy once the correct diagnosis is established. We describe a diagnostically challenging case of a young adult male initially suspected to have metastatic lung cancer, whose evaluation ultimately suggested a previously uncharacterized autoinflammatory process. We present a 26-year-old previously healthy male with progressive dry cough, exertional dyspnea, diffuse myalgias, small joint arthritis involving the fingers, wrists, and ankles, tendonitis, a Gottron-like rash on the hands and lower extremities, low-grade fevers, and occasional bloody stools. Initial external workup revealed a right infrahilar mass, right lower lobe pleural thickening, small pleural effusion, and mediastinal and hilar lymphadenopathy on CT chest, with corresponding PET activity. Initially suspected to have metastatic lung cancer, he was informed his prognosis was poor. However, transbronchial, EBUS, and mediastinal lymph node biopsies showed only active inflammation without malignancy. On presentation to our facility, a broad differential was pursued, with suspicion for an autoinflammatory or autoimmune etiology. Pulmonary function testing was normal. Laboratory evaluation revealed ESR >100, elevated CRP, positive ANA (1:160), negative HLA-B27, normal ferritin, and negative S100 staining. Cytokine analysis showed elevated TNF, IL-6, MCP-1, IL-2, and IL-18. Targeted variant testing identified a UBA1 gene variant, c.123G>T p.(M41L), with low-level mosaicism (0.004%), and a heterozygous MEFV mutation. Although his ethnicity made Familial Mediterranean Fever unlikely, these findings raised the possibility of overlapping somatic and germline contributions to innate immune activation. He was treated empirically with immunosuppression for a presumed multisystem inflammatory disorder, resulting in resolution of symptoms and marked radiologic improvement. This case highlights the expanding spectrum of adult-onset autoinflammatory diseases that may present with pulmonary findings mimicking malignancy. The coexistence of low-level UBA1 mosaicism and MEFV mutation suggests a potential interaction between somatic and inherited variants in triggering inflammation. Similar to the recent discovery of VEXAS syndrome, this case may represent a novel subtype of autoinflammatory disease. Continued genomic and immunologic investigation is warranted, as timely recognition and immunosuppressive therapy can lead to dramatic recovery. This abstract is funded by: None

Abstract Introduction Mediastinal masses may exhibit various clinical and pathological features. Posterior mediastinal lesions are often neurogenic, followed by lymphadenopathy, extramedullary hematopoiesis, paraspinal abscess, and rarely, foregut duplication cysts (prevalence: 0.122%). Given the rarity and diagnostic challenges, these masses are often biopsied, though may not be ideal. We present a case of esophageal duplication cyst (EDC). Case presentation A 33-year-old woman with mild intermittent asthma, had initially presented to an outside facility for chronic productive cough, episodic chest tightness and dyspnea both at rest and with exertion, inspiratory and expiratory wheezes. Despite multiple courses of prednisone for presumed asthma exacerbation, her symptoms persisted. An initial Computer Tomography (CT) Chest demonstrated a 5 x 4 x 3 cm mass within the visceral mediastinum. Bronchoscopy with endobronchial ultrasound and transbronchial needle aspiration of the mediastinal lymph nodes was nondiagnostic, showing scant lymphocytes and abundant mucin. Broad autoimmune, connective tissue disease, and infectious disease workups were negative, prompting referral to our facility. Physical exam and labs were unremarkable and pulmonary function testing showed no evidence of small airway obstruction. A High-Resolution CT Chest revealed a 3.1 x 3.7 x 4.5 cm noncalcified, well-circumscribed mass soft tissue density, adjacent to the esophagus with elevated Hounsfield units close to esophagus. Ultimately duplication cyst was suspected and Magnetic Resonance Imaging (MRI) with contrast showed high T1 and T2 signal within the lesion and no enhancement after contrast, deemed compatible with proteinaceous/hemorrhagic cyst (Figure 1 A-D). Biopsy was deferred given diagnostic MRI characteristics, and risk of secondary infection. The diagnosis of EDC was confirmed via multidisciplinary thoracic tumor board revision. Ultimately, she was referred for surgical resection. Discussion The incidence of EDC is 1 in 8,200, with a two-fold male prevalence over women. These patients may present with dysphagia, cough, stridor, pain, or arrhythmia since childhood, or may be entirely asymptomatic. EDCs can develop along the esophagus, with 90% lacking communication with the esophageal lumen. Although posterior mediastinal mass typically require biopsy to exclude malignancy, tissue biopsy should be avoided in cases with suspected duplication cyst given risk of infection, abscess formation and mediastinitis. Transesophageal endoscopic ultrasonography could further characterize the cyst, however MRI is considered the gold standard diagnostic modality. Conclusion MRI is the gold standard diagnostic modality of EDC. Biopsy should be avoided given the risk of infection. Clinicians should consider a broad differential for posterior mediastinal mass and avoid unnecessary invasive testing.

Abstract Introduction Lung involvement is common in ANCA-associated vasculitis (AAV), presenting in various forms: necrotizing granulomatous inflammation, tracheobronchial inflammation, pulmonary capillaritis and diffuse alveolar hemorrhage (DAH), interstitial lung disease (ILD), and asthma.1 Radiologic manifestations are diverse, often complicating diagnosis based on imaging alone. Typical patterns include lung nodules, cavitation, pulmonary hemorrhage, and peripheral consolidation; however, cystic-like lesions are rarely seen.2 We present a case of AAV with bilateral cystic-like lung lesions. Case presentation A 54-year-old male with childhood asthma initially presented to an outside hospital due to progressive exertional dyspnea for 6 years and dysphonia for 1 year. Initial computer tomography (CT) revealed pulmonary cysts (Figure 1), and a CT-guided biopsy of a right upper lobe cystic lesion revealed intra-alveolar hemorrhage, though pathology was non-diagnostic. He received a diagnosis of congenital cystic lung disease and prescribed Trelegy and fluticasone inhalers. He was instructed to take oral prednisone with taper whenever dyspnea recurs for presumed asthma exacerbation. His exertional dyspnea indeed respond to prednisone but not to inhalers, and it would recur a few weeks later, and his dysphonia persisted. He came to our facility for second opinion given being told lung transplantation is the only ultimate treatment in his case. Additional history revealed chronic ear infection, bilateral rupturesd tympanic membrane, chronic rhinosinusitis, and recurrent nasolacrimal duct infection. He had been on oral prednisone for 4 weeks and remained on 10mg daily. Physical exam noted inspiratory wheezing. Further workups were notable for normal eospinophils, normal renal function, positive C-ANCA and PR3, normal pulmonary function test. High-resolution CT deomnstrated numerous areas of parenchymal lucency with circumferential surrounding groundglass opacity (GGO). At this point, the diagnosis of PR3-AAV is made. Patient is subsequently referred to rheumatology for further management. Discussion The diagnosis of AAV relies on clinical, serologic, radiologic, and pathologic data. The atypical presentation may delay diagnosis, especially in cases limited to ear, nose, and throat involvement and the radiological findings are of low specificity.3 While cystic lesions in AAV-related interstitial pneumonia are documented4, this case lacked a defined cyst wall. The central lucency may present partially destroyed lung parenchyma due to GPA-related necrosis (emphysema or pneumatocele) with surrounding areas of blood products deposited from prior peri-lesional hemorrhage. Clinicians should consider a broad differentials when encounter a cystic-like lesion with thorough history-taking being essential.

Abstract Introduction Unilateral pulmonary vein atresia (UPVA) is a rare congenital anomaly involving absent or obstructed pulmonary veins (PV), often leading to chronic pulmonary venous stasis, recurrent infections, and hemoptysis. Although typically diagnosed in infancy, UPVA can present in adulthood. This report presents a 63-year-old male referred as a case of chronic thromboembolic pulmonary disease (CTEPD) who was diagnosed with UPVA. We describe the diagnostic complexities and potential explanation for loss of pulmonary artery (PA) perfusion in such cases. Case Presentation A 63-year-old man was referred to rule out CTEPD. His past medical history included coronary artery disease and sleep apnea. He presented with chronic cough, repeated hemoptysis, recurrent pneumonias requiring prolonged antibiotics use, and progressive exertional dyspnea. Physical examination was unremarkable. Pulmonary function tests showed moderate restriction and moderately-reduced diffusion capacity. A ventilation-perfusion (V/Q) scan revealed complete absence of perfusion in the left lung. [figure1] High-resolution CT revealed a straight left atrial border sign with absent left superior and inferior PVs, left pulmonary arterial tree hypoplasia, hypoplastic left lung with fibrotic changes due to chronic venous-lymphatic engorgement and pulmonary hypoperfusion. CT also showed compensatory right lung hyperinflation and bronchial artery collaterals. Echocardiography indicated an atrial septal defect (ASD) with no pulmonary vascular disease. Based on CT angiography, UPVA was considered the leading diagnosis. Discussion UPVA is a congenital disease rarely presenting in adulthood with recurrent infections, hemoptysis, and fibrosis. It often accompanies congenital cardiac conditions, like ASD in our case. Pulmonary angiography may reveal ipsilateral PA hypoplasia and atrophied peripheral vessels. The absence of perfusion in the V/Q scan could be explained by reversed blood flow in the PA from congestion caused by the atretic PVs and ipsilateral backflow from the bronchial arteries collaterals. Differential diagnosis like CTEPD was excluded due to atypical complete loss of perfusion of the left lung, and lack of the other radiological stigmata. Swyer-James-MacLeod syndrome was excluded due to a mismatched perfusion defect. Proximal Interruption of the PA was also excluded due to normally developed proximal left and right PAs. Imaging is crucial in showing absent PVs and hypoplastic ipsilateral lung. Conservative management for UPVA is recommended. Given recurrent infections and hemoptysis, pneumonectomy can be considered. Conclusion This case illustrates the atypical presentation of UPVA as a CTEPD mimicker, presenting with absent pulmonary perfusion unilaterally, which can be explained by reversed pulmonary flow secondary to venous engorgement and backflow from bronchial artery collaterals. Figure1:

Objective. To determine whether results of the nasopharyngeal FilmArray respiratory panel (NP-FARP) influenced antibiotic decisions. Methods. We reviewed the medical records of nonintensive care unit (ICU) inpatients that had an NP-FARP performed at our institution between June 2013 and June 2014. The inpatient records were reviewed 48 hours after the NP-FARP for the following data: demographic information; NP-FARP, serum procalcitonin, and methicillin-resistant Staphylococcus aureus nasal swab (MRSA NS) results; antibiotics prior and post-48 hours of the NP-FARP result; and the current immunosuppression status. Clinical outcome data were not obtained. Patients were categorized into those who had a positive (+) or a negative (−) NP-FARP. We further subdivided these two categories into groups A, B, and C based on the antibiotic modifications 48 hours after their NP-FARP result. Group A included patients who were never initiated on antimicrobial therapy. Patients whose antibiotics were discontinued or deescalated were placed in group B. Patients with antibiotic escalation or continuation without change constituted group C. We compared and analyzed groups A, B, and C in the (+) and (−) NP-FARP cohorts. Results. A total of 545 patients were included. There were 143 (26%) patients with positive and 402 (74%) patients with negative NP-FARPs. Comparison of groups A, B, and C between those with a (+) and (−) NP-FARP were as follows: (+) A and (−) A, 28/143 (20%) and 84/402 (21%); (+) B and (−) B, 59/143 (41%) and 147/402 (37%); and (+) C and (−) C, 56/143 (39%) and 171/402 (43%), respectively. We found no statistically significant differences between groups (+) A versus (−) A, (+) B versus (−) B, and (+) C versus (−) C with respect to age, gender, MRSA NS result, procalcitonin result, or concurrent immunosuppression. Conclusion. In non-ICU inpatients, NP-FARP alone or in combination with procalcitonin or MRSA NS did not influence antibiotic decisions during the study period.

Background. The FilmArray Respiratory Panel (FARP) (BioFire Diagnostics, Inc.) is a multiplex, polymerase chain reaction (PCR) technique that can detect 17 respiratory viruses and 3 bacterial targets in a single reaction. Immunocompromised hosts (ICH) with respiratory illnesses often undergo bronchoscopy with bronchoalveolar lavage (BAL). This prospective study aimed to evaluate the yield and concordance of NP and BAL FARP testing when performed on the same patient concurrently. Methods. From February to December 2016, 125 patients (100 ICH and 25 non-ICH) were enrolled. NP swabs and BAL samples were sent for FARP testing. Results. The yield of the BAL FARP among ICH and non-ICH was 24% (24/100) and 8% (2/25), respectively. The yield of positive NP swabs in ICH was 27% (27/100) versus 4% (1/25) in non-ICH. The majority of patients (89%; 111/125) had concordant results between NP and BAL specimens. Of the 24 ICH patients who had a positive BAL FARP, the majority (79%) had the same pathogen detected from the NP swab. Conclusion. The FARP may be useful in the ICH. Given the high concordance, in patients whom a pathogen is identified on the NP FARP, a FARP performed on BAL will likely yield the same result. However, if the NP FARP is negative, performing the test on a BAL sample may have an incremental yield.