Citations

Objective Diffuse alveolar hemorrhage (DAH) is a life‐threatening presentation of antineutrophil cytoplasmic antibody–associated vasculitis (AAV). Patients with AAV are at an increased risk of venous thromboembolic events (VTEs). These manifestations can co‐occur; however, the prognosis and management of these patients are poorly understood. Methods In this retrospective observational study, we included patients diagnosed with AAV who presented with both DAH and VTE during the same outpatient visit or in the same inpatient treatment episode. Results Among 121 patients with proven DAH secondary to AAV managed at our institution, 14 (11.6%) were also diagnosed with VTE. Patients were predominantly men (71%) with median age at diagnosis of 67 (interquartile range 56–72) years. Five patients were diagnosed with DAH followed by VTE, four patients were diagnosed with VTE before developing DAH (T‐AAV), and five patients were diagnosed with VTE and DAH simultaneously (HT‐AAV). Inferior vena cava filters were placed in 13 patients (93%). Although most patients received systemic anticoagulation within 30 days of DAH diagnosis, anticoagulation management was individualized based on clinical presentation. One patient with preexisting interstitial lung disease died of respiratory failure after initially presenting with pulmonary embolism and later developing DAH during hospitalization. Bleeding complications, including recurrent DAH or retroperitoneal hematoma, were observed in six patients (43%). Three patients (21%) experienced progression or recurrence of VTE within 90 days. Conclusion Management of patients with DAH and VTE is challenging and should be guided by the severity of DAH, additional organ manifestations of AAV, and risk stratification of the presenting VTE.

Interstitial lung abnormalities (ILAs) are incidental nondependent radiologic findings that may portend early or future interstitial lung disease (ILD), but do not meet specific criteria at the time of presentation. They are subclinical by definition and found more commonly in older ever-smokers undergoing computed tomography (CT) imaging for other indications, including cardiac or lung cancer screening programs. As ILA prevalence increases, driven by an aging population and heightened awareness in younger patients, understanding risk factors for their development and progression has gained recent interest, particularly for optimizing subsequent ILD outcomes. This narrative review summarizes current ILA definitions, epidemiology, risk stratification, and management, while highlighting current challenges and knowledge gaps.

Background: Pneumocystis jirovecii pneumonia (PJP) is life-threatening for immunocompromised patients. No consensus exists on PJP prophylaxis for immunosuppressed patients without HIV, transplant, or cancer. Methods: We retrospectively reviewed the electronic health records of adult immunosuppressed patients with PJP diagnosed between 1990 and 2020 at Mayo Clinic. Patients with HIV, solid organ transplants, or cancer were excluded. Demographic data, treatments, and outcomes were manually abstracted. Results: The most common indications for immunosuppression were rheumatoid arthritis (19.7%), vasculitis (18.1%), and interstitial lung disease (ILD) not related to connective tissue disease (17.6%). Despite having high risk of PJP, 86.0% of patients did not receive PJP prophylaxis. Corticosteroids were the most common immunosuppressive agent used (84.5%), with 64.4% of patients receiving high-dose treatment. Nonbiologic disease-modifying antirheumatic drugs were used for 49.7%, including methotrexate (51.0%), azathioprine (22.9%), and hydroxychloroquine (11.5%). Biologics were prescribed for 25.4%, primarily rituximab (59.2%) and infliximab (22.4%). Hospitalization occurred for 76.7% of patients; 70.3% required intensive care unit (ICU) admission, and 46.6% received mechanical ventilation. The in-hospital mortality rate was 30.4% overall and 53.6% for patients on ventilation. Predictors of death included ILD [odds ratio (OR), 4.61; 95% CI, 1.75-13.00], ICU admission (OR, 3.60; 95% CI, 1.19-11.08), and ventilator use (OR, 3.46; 95% CI, 1.30-9.79). Biologic use was associated with lower odds of death (OR, 0.34; 95% CI, 0.11-0.89). Conclusions: Most patients in our cohort did not receive PJP prophylaxis, and outcomes were poor with high mortality rates. Standardized risk stratification and prophylaxis protocols are needed to improve outcomes.

ABSTRACTWe describe a case of a 56‐year‐old male who developed severe, refractory hypotension after an intentional ingestion of clozapine and who became hemodynamically stable after one session of therapeutic plasma exchange (TPE). The patient, who presented after an ingestion of clozapine, was found to have altered mental status and hypotension in the emergency department. Escalating catecholamine vasoactive agents were necessary to maintain adequate hemodynamics. Angiotensin II was added and rapidly up titrated in efforts to maintain adequate blood pressure. Due to persistent hemodynamic instability despite four vasoactive agents, TPE was attempted to enhance the elimination of the highly protein bound medication. Within 2 h of completing TPE, the catecholamines and vasopressin were stopped, and angiotensin II dosing was significantly decreased. This is the first report of utilizing TPE as a method of enhanced elimination of a toxic clozapine ingestion resulting in severe hemodynamic compromise. Further study is necessary to determine if TPE should be incorporated into the care of patients experiencing clozapine toxicity.

Abstract Introduction: Pulmonary nodules are not uncommonly found in patients with Sjogren's disease. Although they frequently can be benign, nodules in the context of systemic autoimmune disease such as Sjogren's disease require broadened differentials including lymphoid intersitial pneumonia, follicular bronchiolitis, nodular lymphoid hyperplasia (NLH), amyloidosis and lung malignancy. Although lung carcinoma can occur, the most frequent malignant etiology is non-Hodgkin's lymphoma, including pulmonary extranodal marginal zone lymphoma of mucosa associated lymphoid tissue (MALT lymphoma). On the other hand, many of these differentials are benign; however, some such as NLH can progress to lymphoma while others such as nodular amyloidosis can be associated with MALT lymphoma. As pulmonary MALT lymphoma often presents with asymptomatic nodules or consolidations, the index of suspicion by pulmonologists is crucial for diagnosis. Description: A 66 year old female nonsmoker presented with incidentally found bilateral solid and subsolid pulmonary nodules, the largest being 1.3 centimeters in the left lower lobe, in the context of calcified lymph nodes and splenic and liver calcified granulomas. As she was asymptomatic, possible differentials included chronic granulomatous disease, inflammatory/autoimmune lesions and less likely multifocal pulmonary malignancy. Fungal serologies were negative. Antinuclear antibodies, SS-A, and SS-B serologies were strongly positive. Erythrocyte sedimentation rate and rheumatoid factor were also positive. Further diagnostic workup led to a diagnosis of Sjogren's disease. Repeat 3 month CT chest showed stability of the lymphadenopathy and pulmonary nodules. However, despite stability, our pre-test probability for neoplastic pulmonary nodules had increased due to her autoimmune diagnosis. PET-CT scan was completed, showing metabolically active nodules bilaterally with a SUV range of 2-3.5, with the largest nodule having the highest uptake. Transbronchial biopsy of the largest nodule was consistent with MALT lymphoma. Discussion: The diagnosis of Sjogren's disease led to more aggressive efforts towards diagnostic certainty including a PET-CT scan and ultimately transbronchial biopsy. It is postulated that autoimmune activity in the pulmonary lymphoid tissue is what gives rise to MALT lymphoma. In one retrospective study on pulmonary nodules in patients with Sjogren's disease, greater than 70% of biopsied nodules were malignant, of which half represented MALT lymphoma. MALT lymphoma is diagnosed at the stage of disseminated disease in one third of cases, frequently recurs and has potential for aggressive transformation. Therefore, in the case of multiple pulmonary nodules in patients with Sjogren's disease, the evidence of underlying autoimmunity should increase the index of suspicion for pulmonary malignancy, including MALT lymphoma.

Abstract Introduction: Eosinophilic Granulomatosis with Polyangiitis (EGPA) is an ANCA-associated vasculitis (AAV) that causes eosinophil-rich granulomatous vasculitis affecting small vessels. While pulmonary manifestations of EGPA are diverse, development of pulmonary fibrosis is rare. We present two cases of EGPA with pulmonary fibrosis.Case 1: A 31-year-old female with refractory asthma, chronic rhinosinusitis, recurrent ear infections, presented with productive cough, dyspnea, wheeze with relief from antibiotics and steroids. Labs noted peripheral eosinophilia, elevated IgE, P-ANCA positivity with equivocally positive PR3 antibody. CT chest revealed bilateral lower lobe predominate honeycombing, traction bronchiectasis, subpleural reticulations indeterminate for UIP. Pulmonary function tests (PFTs) noted complex restriction with mildly reduced diffusion capacity of carbon monoxide (DLCO). Exhaled nitric oxide (ENO) was elevated at 132 parts per billion (ppb) (normal <39 bbp). Bronchoalveolar lavage (BAL) demonstrated eosinophilia. CT of the sinuses, infectious workup, anti-cyclic citrullinated peptide antibody (CCP), and genetic testing for hypereosinophilia were negative. Treatment with prednisone and Mepolizumab months led to significant improvement of respiratory symptoms.Case 2: A 69-year-old man with refractory allergic rhinitis and chronic sinusitis, gastroesophageal reflux (GERD) presented with eight years of chronic productive cough, dyspnea on exertion, weight loss, dysphagia. Labs noted peripheral eosinophilia, elevated IgE, isolated P-ANCA positivity. CT chest noted peripheral predominant reticulations, traction bronchiectasis, and ground-glass opacities indeterminate for UIP. PFTs noted severe restrictive pattern with reduced DLCO. ENO was elevated at 54 ppb (normal <30 ppb). CT of sinuses noted bilateral mucosal thickening and polyps. BAL and biopsies were unable to be performed prior to prednisone initiation given severity of symptoms and hypoxemia. Prednisone led to dramatic symptom improvement. Mepolizumab initially added but discontinued due to side effects and he denied Mycophenolate due to concern for side effects.Discussion: While pulmonary fibrosis in patients with P-ANCA and MPO positive microscopic polyangiitis (MPA) has been well described, it is rare in EGPA. In cases of ILD associated with EGPA, usual interstitial pneumonia (UIP) is the most common imaging finding, with nonspecific interstitial pneumonia (NSIP) and unclassified interstitial lung disease (ILD) also reported. Fibrosis develops either secondary to eosinophilic release of profibrotic and inflammatory cytokines and deficiency of anti-inflammatory neutrophil extracellular traps (NET), as described with idiopathic eosinophilic pneumonia, or due to overlap with MPA. Similar to MPA, fibrosis in our cases preceded development of systemic vasculitis, although many cases of AAV with pulmonary fibrosis report concomitant systemic vasculitis. Despite adequate initial treatment, fibrosis may progress, requiring antifibrotics.

Abstract Background: Lymphangioleiomyomatosis (LAM) is a rare, female-predominant, low-grade neoplasm that can lead to progressive diffuse cystic lung disease. Pregnancy has been associated with accelerated disease progression and increased risk of spontaneous pneumothoraces in women with LAM. Sirolimus is the current first line treatment for LAM and has demonstrated benefit in stabilizing lung function decline and reducing the risk of spontaneous pneumothoraces; however, there is unclear evidence regarding the risk benefit ratio of the use of sirolimus during pregnancy. Methods: We queried physicians across the LAM Clinic Network and obtained information regarding demographics, baseline characteristics, LAM related complications, lung function, sirolimus dosing, and pregnancy outcomes in women with LAM who took sirolimus during pregnancy. Results: We identified 9 women with LAM who had used sirolimus during pregnancy for a total of 12 pregnancies. All women had sporadic LAM with moderate lung function impairment prior to pregnancy: median FEV1 56% predicted, median DLCO 43% predicted, and 2 patients on supplemental oxygen. Sirolimus was used throughout pregnancy in most instances (10/12 (83.3%)). Sirolimus was held prior to pregnancy in 2 patients; both these patients experienced a spontaneous pneumothorax in the first trimester and resumed sirolimus in the second trimester with no further pneumothoraces during the rest of the pregnancy. The median sirolimus dose during pregnancy was 1 (range 1-2) mg daily with a median trough level of 2.95 (range: 1 – 6.7) ng/ml. Ten pregnancies (83.3%) resulted in live births, 1 pregnancy was terminated due to molar pregnancy, and 1 pregnancy resulted in miscarriage. Spirometry and DLCO were available in 8 pregnancies and tended to be stable (Figure 1). None of the 10 pregnancies that resulted in live births reported any fetal health issues. Seven out of these 10 children (70%) were breastfed with continued sirolimus use. At the time of submission of this report, the median age of these children is 3.5 years (range: 1 – 6.5 years) with no reported adverse health outcomes from sirolimus exposure during pregnancy. Conclusions: The use of sirolimus during pregnancy in women with LAM appears to be safe for both mother and fetus and might help reduce the pregnancy associated risks of accelerated lung function decline and spontaneous pneumothoraces.