Lung transplantation for acute exacerbation of interstitial lung disease.

BACKGROUND: Acute exacerbations of interstitial lung diseases (AE-ILD) have a high mortality rate with no effective medical therapies. Lung transplantation is a potentially life-saving option for patients with AE-ILD, but its role is not well established. The aim of this study is to determine if this therapy during AE-ILD significantly affects post-transplant outcomes in comparison to those transplanted with stable disease. METHODS: We conducted a retrospective study of consecutive patients with AE-ILD admitted to our institution from 2015 to 2018. The comparison group included patients with stable ILD listed for lung transplant during the same period. The primary end-points were in-hospital mortality for patients admitted with AE-ILD and 1-year survival for the transplanted patients. RESULTS: Of 53 patients admitted for AE-ILD, 28 were treated with medical therapy alone and 25 underwent transplantation. All patients with AE-ILD who underwent transplantation survived to hospital discharge, whereas only 43% of the AE-ILD medically treated did. During the same period, 67 patients with stable ILD underwent transplantation. Survival at 1 year for the transplanted patients was not different for the AE-ILD group versus stable ILD group (96% vs 92.5%). The rates of primary graft dysfunction, post-transplant hospital length-of-stay and acute cellular rejection were similar between the groups. CONCLUSION: Patients with ILD transplanted during AE-ILD had no meaningful difference in overall survival, rate of primary graft dysfunction or acute rejection compared with those transplanted with stable disease. Our results suggest that lung transplantation can be considered as a therapeutic option for selected patients with AE-ILD.

Macrophage activating syndrome causing decompensated right heart failure.

BACKGROUND: Macrophage activating syndrome (MAS) is a form of hemophagocytic lymphohistiocytosis (HLH), a rare complication of autoimmune disease that is characterized by cytokine storm and multiorgan failure. CASE SUMMARY: A 32-year-old male presented with acutely decompensated pulmonary arterial hypertension and right heart failure secondary to MAS. The patient was immediately started on inhaled and intravenous epoprostenol, vasopressors and dexamethasone and anakinra were administered. Despite the therapies given, the patient's condition continued to decline, and he was placed on veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. Over a few days, his clinical condition improved, and he was decannulated from VA-ECMO and later transitioned oral treprositinil and was discharged home. Due to its non-specific clinical manifestations, the diagnosis of MAS depends on high clinical suspicion and initial laboratory work up such as thrombocytopenia, transaminitis, hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia, etc. In our patient, MAS led to decompensated Pulmonary Arterial Hypertension (PAH) leading to right heart failure that was refractory to inhaled and intravenous epoprostenol and vasopressors and required VA-ECMO as a bridge to recovery while his MAS was managed by anakinra and dexamethasone. CONCLUSION: MAS can result in acute decompensation of PAH and right heart failure. Besides RV failure management, immunosuppressants such as anakinra, etoposide, etc. should be utilized early in the management of MAS. In refractory right heart failure, VA-ECMO can be considered as a bridge to recovery. There is a paucity of literature supporting the utilization of VA-ECMO in the management of refractory right heart failure caused by MAS in adults and much of the data stems from pediatric studies. This case serves as a fine example of successful use of VA-ECMO in adult population.

Cyclophosphamide for the treatment of Acute Exacerbation of Interstitial Lung Disease: A Review of the Literature.

Acute exacerbation of interstitial lung disease is a serious and life-threatening event but little is known about its treatment. Cyclophosphamide has been proposed in randomized clinic trials as a treatment option in progressive cases of systemic sclerosis related interstitial lung disease. However, in acute exacerbation of interstitial lung disease, we found only small case series, and retrospective studies, mostly with no comparative groups which described the role of cyclophosphamide. Results of these studies showed mixed outcomes, with no robust evidence that cyclophosphamide adds any benefit in treating acute exacerbations of interstitial lung disease. More well-designed studies including randomized clinical trials are needed to better understand the role of cyclophosphamide during exacerbations of interstitial lung disease. In this review article, we summarize the current evidence on the use of cyclophosphamide in interstitial lung disease with a focus on the acute exacerbation events.

Ustekinumab associated chronic eosinophilic pneumonia.

INTRODUCTION: Ustekinumab-induced eosinophilic pneumonia is rare and to our knowledge, this is the fifth reported case of such an entity. CASE STUDY: A 60-year-old female was admitted with worsening shortness of breath and a nonproductive cough for 4 months. Her past medical history was significant for Crohn's disease and psoriatic arthritis that was previously managed with adalimumab and switched to ustekinumab 2 months before symptoms. Initial diagnostic workup showed 10% peripheral eosinophilia and a CT chest showed numerous 5 mm nodules scattered throughout the lungs along with some peripheral reticulations. Her BAL fluid analysis showed abnormally high eosinophil count (67%), greatly limiting her potential diagnoses to eosinophilic pneumonia, EGPA, and tropical pulmonary eosinophilia (TPE). AEP typically causes more severe disease with a rapid onset, and there was low suspicion for TPE based on history, leaving EGPA and CEP. Based on her negative autoimmune serology, a negative biopsy of the nasal mucosa (no vasculitis/granulomata or eosinophils), and negative infectious workup, the patient was diagnosed with CEP secondary to ustekinumab and the drug was stopped. She was started on high dose prednisone and after a prolonged taper over 5 months, her symptoms and nodules and reticulations on her CT scan resolved. DISCUSSION: This case exemplifies the importance of identifying drug-induced lung diseases which in many cases might not have a strong temporal association with the symptom onset. It also highlights that some drugs owing to their long elimination half-time can remain in the system for a prolonged period and continues to cause symptoms despite their cessation and require prolonged treatment and reassurance. CONCLUSION: The association of eosinophilic pneumonia with ustekinumab, a drug used in the treatment of psoriasis and other autoimmune diseases, is rare and there is a paucity of literature regarding this association.

First case of minimal change nephrotic syndrome resolving with antifungal therapy for isolated pleural cryptococcal infection.

We report the case of a 71-year-old male with poorly controlled diabetes mellitus who presented with lower extremity edema and acute renal failure. He was diagnosed with nephrotic syndrome secondary to minimal change disease (MCD). Treatment with steroids was withheld due to concern for hyperglycemia in the context of his poorly controlled diabetes mellitus. A week after discharge, he was subsequently re-hospitalized four times within a month with pleural effusions, dyspnea, and fever. Work up revealed isolated pleural cryptococcosis, demonstrated on two separate admissions. There was neither evidence of disseminated disease nor immunocompromising condition. Immunosuppression was not initiated for the treatment of MCD in the setting of poorly controlled diabetes and active infection. After six months of treatment with fluconazole 400 mg/day, the nephrotic syndrome, renal failure, and cryptococcal pleuritis resolved. This case is the first to our knowledge of isolated pleural cryptococcosis associated with nephrotic syndrome. The patient's course lends further support to the hypothesis that there may be causal relationship between cryptococcosis and nephrotic syndrome.

Pulmonary Embolism in Acute Asthma Exacerbation: Clinical Characteristics, Prediction Model and Hospital Outcomes.

PURPOSE: Little is known about the characteristics and impact of acute pulmonary embolism (PE) during episodes of asthma exacerbation. We aimed to characterize patients diagnosed with acute PE in the setting of asthma exacerbation, develop a prediction model to help identify future patients and assess the impact of acute PE on hospital outcomes. METHODS: We included 758 patients who were treated for asthma exacerbation and underwent a computed tomographic pulmonary angiography (CTA) during the same encounter at a university-based hospital between June 2011 and October 2018. We compared clinical characteristics of patients with and without acute PE and developed a machine learning prediction model to classify the PE status based on the clinical variables. We used multivariable regression analysis to evaluate the impact of acute PE on hospital outcomes. RESULTS: Twenty percent of the asthma exacerbation patients who underwent CTA had an acute PE. Factors associated with acute PE included previous history of PE, high CHA2DS2-VASc score, hyperlipidemia, history of deep vein thrombosis, malignancy, chronic systemic corticosteroids use, high body mass index and atrial fibrillation. Using these factors, we developed a random forest machine learning prediction model which had an 88% accuracy in classifying the acute PE status of the patients (area under the receiver operating characteristic curve = 0.899; 95% confidence interval: 0.885-0.913). Acute PE in asthma exacerbation was associated with longer hospital stay and intensive care unit stay. CONCLUSION: It is important to consider acute PE, a potentially life-threatening event, in the setting of asthma exacerbation especially when other risk factors are present.

Chronic Right Heart Failure: Expanding Prevalence and Challenges in Outpatient Management.

Right heart failure is caused by right heart dysfunction resulting in suboptimal stroke volume to supply the pulmonary circulation. Therapeutic developments mean that patients with acute right heart failure survive to hospital discharge and live with chronic right heart failure. Chronic right heart failure management aims to reduce afterload, optimize preload, and support contractility, with the best evidence available in vascular targeted therapy for pulmonary arterial hypertension. However, the management of chronic right heart failure relies on adapting therapies for left ventricular heart failure to the right. We review right heart failure management in the ambulatory setting and its challenges.

Mesenteric lymphadenitis as a presenting feature of Whipple's disease.

Detecting Whipple's disease, a "great imitator", requires a high index of suspicion so that antimicrobial treatment can be initiated in a timely manner; a missed diagnosis can be fatal. Although an uncommon cause, Whipple's disease must be considered in adults with mesenteric lymphadenitis. We report the case of a 39-year-old African American man who presented with chronic joint pain, chronic weight loss, and acute onset epigastric pain. Contrast-enhanced computed tomography of the abdomen and pelvis showed extensive mesenteric lymphadenopathy. A diagnosis of Whipple's disease was made based upon demonstration of PAS-positive macrophages in the mesenteric lymph node and duodenal biopsies. Antimicrobial therapy resulted in weight gain and resolution of abdominal pain and arthralgia at six months follow-up. Whipple's disease can be fatal without antibacterial therapy and it always needs to be considered in individuals presenting with any combination of abdominal pain, weight loss, and diarrhea in the background of nonspecific arthritis or arthralgia. Whipple's disease must also be considered in adults presenting with mesenteric lymphadenitis. Review of CT scans may be helpful, as Whipple's disease characteristically causes low attenuation mesenteric lymphadenopathy.