A Fatal Case of Diffuse Alveolar Hemorrhage in the Setting of Systemic Lupus Erythematosus: A Case Report and Review of Noninfectious Causes of Acute Pulmonary Hemorrhage in Adults

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease, characterized by autoantibody production and immune complex formation, that has the potential to affect virtually any organ. Pleuropulmonary involvement occurs in 50–70% and commonly manifests as pleuritis and pleural effusion. Diffuse alveolar hemorrhage (DAH) is a rare manifestation of SLE. Most cases of DAH occur in young adults with an underlying autoimmune disease such as systemic vasculitis or Goodpasture syndrome. SLE is typically lower on the list of initial differential diagnoses of DAH due to its rarity compared to other etiologies. We present a case of a patient with dyspnea on exertion, dry coughs, lower extremity edema, and intermittent periorbital edema who ultimately succumbed to respiratory failure secondary to DAH in the setting of SLE. The diagnosis of SLE was suspected clinically and confirmed at autopsy due to her rapid clinical deterioration. DAH requires prompt intervention, and management is guided by the underlying disease process. SLE is a potentially treatable disease; therefore, timely diagnosis is important in order to exclude other noninfectious causes of DAH (reviewed in this report) and to initiate appropriate therapy.

Diffuse Alveolar Hemorrhage as a Life-Threatening Feature of Juvenile Onset Systemic Lupus Erythematosus: A Case-Based Review

“…Diffuse alveolar hemorrhage is an unpredictable and devastating disorder characterised by intraalveolar bleeding from damaged pulmonary vasculature with a mortality rate of 20%. 6 Differential diagnosis of non-infectious causes of DAH includes coagulopathy; exposure to several drugs including abciximab, amiodarone, anticoagulants, carbimazole, crack cocaine, leflunomide, nitrofurantoin, penicillamine, propylthiouracil, sirolimus, TNF-α antagonist, and trimellitic anhydride; mitral stenosis or regurgitation; and autoimmune diseases. 6 , 7 The autoimmune diseases associated with DAH include granulomatosis with polyangiitis, microscopic polyangiitis, Goodpasture syndrome, antiphospholipid syndrome, isolated pauci-immune pulmonary capillaritis, idiopathic pulmonary hemosiderosis, and SLE.…”

“… 6 Differential diagnosis of non-infectious causes of DAH includes coagulopathy; exposure to several drugs including abciximab, amiodarone, anticoagulants, carbimazole, crack cocaine, leflunomide, nitrofurantoin, penicillamine, propylthiouracil, sirolimus, TNF-α antagonist, and trimellitic anhydride; mitral stenosis or regurgitation; and autoimmune diseases. 6 , 7 The autoimmune diseases associated with DAH include granulomatosis with polyangiitis, microscopic polyangiitis, Goodpasture syndrome, antiphospholipid syndrome, isolated pauci-immune pulmonary capillaritis, idiopathic pulmonary hemosiderosis, and SLE. Although DAH mostly occurs in young adults with autoimmune diseases, its association with those diseases other than SLE has rarely been reported in children.…”

“…Although DAH mostly occurs in young adults with autoimmune diseases, its association with those diseases other than SLE has rarely been reported in children. 6 , 7 In this paper, we briefly reviewed the literature relevant to pulmonary hemorrhages associated with jSLE.…”

Regulation of cGAS Activity and Downstream Signaling

“…However, in AGS, the mutation in DNAses leads to the amassing of cytosolic DNA resulting in the overactivation of cGAS-STING signaling to generate IFN-β [ 136 , 137 ]. Similarly, in SLE increased IFN-β generation affects various cells and organs such as blood, lung, interstitial, kidney, and skin [ 138 , 139 , 140 ]. Thus, the cGAS-STING signaling pathway in macrophages and T cell may serve as a connecting link between innate immunity and adaptive immunity [ 141 ].…”