Preface
Autoimmune diseases are characterized by disturbances in immune regulation leading to the production of specific autoantibodies, causing inflammation and multi-organ involvement. A distinction should be made between connective tissue disease, which involves systemic lupus erythematosus, systemic scleroderma, inflammatory muscle disease, and rheumatoid arthritis, and vasculitis, which is mainly involved in small vessel vasculitis such as ANCA-associated vasculitis.
Intensive care unit (ICU) admission in patients with autoimmune diseases is often due to disease recurrence, infection, and organ failure, and is associated with high mortality. At the same time, the management of these patients, including timely identification of the disease, initiation of immunosuppressive therapy, and life-sustaining therapy, is often complex and requires multidisciplinary involvement. Based on this, foreign scholars reviewed the diagnosis and management of critical clinical conditions of autoimmune diseases, and summarized the epidemiology, clinical characteristics and management of five major severe autoimmune diseases. Here is an excerpt of some of its contents for the benefit of readers.
Scleroderma crisis
Patients with scleroderma are prone to life-threatening complications and are admitted to the ICU for further treatment. Predominantly non-scleroderma-related causes (71.4%) or respiratory complications.
Scleroderma renal crisis (SRC)
Scleroderma renal crisis (SRC) is a rare (approximately 2.4% of patients with scleroderma) but critical complication, with a 5-year survival rate of 50-70%. SRC typically presents with malignant hypertension and oliguric acute kidney injury. Left-sided ventricular insufficiency and hypertensive encephalopathy are common. SRC is more common in patients taking glucocorticoids and can be triggered by nephrotoxic drugs or volume depletion.
Microangiopathic hemolytic anemia was present in 43% of patients, and anti-RNA polymerase III antibodies were present in one-third patients. SRC needs to be differentiated from ANCA-positive rapidly progressive glomerulonephritis because of differences in treatment and patient management.
The mainstay of treatment is aggressive blood pressure control, including angiotensin-converting enzyme inhibitors and other antihypertensive drugs, with calcium-channel blockers if necessary. β blockers can exacerbate Raynaud's phenomenon and should be avoided. Patients usually require dialysis, and some patients require a kidney transplant.
Scleroderma cardiac crisis
Scleroderma cardiac crisis is an uncommon but life-threatening complication that is common in patients with a recent onset and vascular phenotype (including severe Raynaud's phenomenon, finger ulcers, massive telangiectasias, and pulmonary hypertension). Scleroderma cardiac crisis is characterised by acute left ventricular dysfunction that is usually reversible but is associated with a poor long-term prognosis (6-month survival rate of 44%).
Pulmonary-renal syndrome
Cormonary-renal syndrome is characterized by diffuse alveolar hemorrhage and necrotizing glomerulonephritis. The most common causes of pulmonary-renal syndrome are ANCA vasculitis (~70%) and antiglomerular basement membrane (GBM) disease (~20%). Acute respiratory failure (ARF) requiring invasive mechanical ventilation occurs in approximately 50% of patients. Cormonary-renal syndrome needs to be differentiated from other common ICU conditions such as sepsis. Bronchoscopy is required to rule out infection and evaluate for evidence of diffuse alveolar hemorrhage. Percutaneous renal biopsy can be histologically diagnostic, and lung biopsy is riskier and may be considered as an alternative.
Acute interstitial lung disease (connective tissue-related ILD)
Interstitial lung disease (ILD) is a rare parenchymal lung lesion characterized by interstitial abnormalities and sometimes fibrotic manifestations that account for ~15% of patients with connective tissue disease (predominantly rheumatoid arthritis, scleroderma, myositis, Sjögren's syndrome, mixed CTD, and SLE).
Many myositis-associated ILDs do not have elevated creatine kinase or muscle symptoms. Nonspecific interstitial pneumonia is the most common type, but interstitial pneumonia vulgaris (rheumatoid arthritis, scleroderma, myositis) can also occur. High-resolution CT, alveolar lavage, and autoantibody testing are essential to confirm the diagnosis and rule out other causes (infection, drug toxicity). Lung biopsy is usually not required.
Although alveolar lavage fluid can help provide useful diagnostic information, the correlation between alveolar lavage fluid properties and prognosis or response to treatment is weak. Cases of rapid progression to acute respiratory distress syndrome (ARDS) have also been reported, particularly in patients with scleroderma, antisynthetase, or antimelanoma differentiation-related gene 5 (aMDA-5) syndrome, with a poor prognosis (case fatality rate > 50%). Pulmonary fibrosis and pulmonary hypertension are other major prognostic factors.
With the exception of scleroderma, glucocorticoids are first-line treatments, usually in combination with immunosuppressants, mainly cyclophosphamide or mycophenolate mofetil. Other promising drug treatments include tacrolimus, rituximab, and Janus kinase (JAK) inhibitors (tofacitinib). In some patients, extracorporeal membrane oxygenation (ECMO) may be tried as a bridging modality for transplantation.
Acute severe cytopenias
Hematologic abnormalities are common in autoimmune diseases. Autoimmune cytopenias such as autoimmune hemolytic anemia (predominantly warm IgG direct antiglobulin test) and idiopathic thrombocytopenic purpura are rare but sometimes present with life-threatening complications that are common in SLE (~10% and ~15%, respectively).
Thrombotic microangiopathy is diagnosed only by the presence of red blood cell fragments (eg, fissures) on peripheral blood smear if thrombocytopenia and hemolytic anemia coexist, and other potential causes include thrombotic thrombocytopenic purpura (sometimes associated with SLE, mixed CTD), SRC, and catastrophic antiphospholipid syndrome (CAPS). Patients with pancytopenia require bone marrow aspirate.
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In addition to infection, drug toxicity, and malignancy, hemophilic lymphohistiocytosis (HLH) and myelonecrosis are the most common causes, and HLH is a life-threatening hyperinflammatory state characterized by hyperthermia, hepatosplenomegaly, bilineage cytopenia, and macrophage activation at hematopoietic sites.
HLH can be predisposed by infection (particularly Epstein-Barr virus, cytomegalovirus, or human immunodeficiency virus), lymphocytic tumors (B or T-cell lymphoma), connective tissue diseases (mainly lupus and Still's disease), or drugs. Clinical manifestations need to be differentiated from common ICU conditions such as sepsis, multiple organ dysfunction syndrome, and diffuse intravascular hemolysis.
Fardet proposed a diagnostic criterion based on 9 criteria: 3 clinical criteria (underlying immunosuppressive status, high fever, hepatosplenomegaly); 5 biochemical criteria (cytopenias, elevated triglycerides, ferritin and serum aspartate aminotransferase (SGOT), decreased fibrinogen); and 1 cytology criterion (characteristic haemophilia on bone marrow aspirate). The HScore total score ranges from 0 to 337, with a < 1% chance of haemophilic syndrome when the HScore ≤ 90 points, and more than 99% chance of haemophilic syndrome when the HScore ≥ 250 points. A study of 71 patients with HLH admitted to the ICU reported an in-hospital case fatality rate of 68%.
灾难性抗磷脂综合征（CAPS）
CAPS is caused by antiphospholipid antibodies that activate endothelial cells, platelets, and immune cells, causing inflammation and pre-thrombotic manifestations. It is usually triggered by infection, surgery, or medications. CAPS most commonly affects the kidneys, lungs, heart, central nervous system, skin, liver, and digestive tract. The kidneys present with hypertension and acute kidney injury. CAPS is histologically characterized by acute thrombotic microangiopathy and needs to be differentiated from hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, diffuse intravascular coagulation, and heparin-associated thrombocytopenia. The diagnostic criteria for CAPS can be divided into "confirmed CAPS" episodes and "suspected CAPS" episodes. However, this diagnostic criterion has certain limitations.
A French multicenter study (24 ICUs) examined patients with positive anticardiolipin antibodies and any new thrombotic manifestations. According to this criterion, patients were divided into "confirmed CAPS" episodes (N=11, 7.2%), "suspected CAPS" episodes (N=60, 39.5%), and no CAPS episodes (N=81, 53.3%). A common reason why CAPS cannot be classified as "confirmed CAPS" is the lack of histologic evidence of microvascular thrombosis. Overall, 35/152 (23%) episodes were fatal, with comparable mortality rates between confirmed/suspected CAPS and no CAPS, and similar haematology findings between groups, suggesting that some patients did not meet the diagnostic criteria for CAPS but were in fact "close to CPAS". In the future, further exploration of the adequacy of using CAPS criteria to evaluate critically ill patients with antiphospholipid syndrome is needed.
参考文献：Dumas G, Arabi YM, Bartz R, Ranzani O, Scheibe F, Darmon M, Helms J. Diagnosis and management of autoimmune diseases in the ICU. Intensive Care Med. 2024 Jan; 50(1):17-35. doi: 10.1007/s00134-023-07266-7.
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