A 72-year-old woman with hypertension, hypothyroidism, and a history of giant cell arteritis (GCA) presents with acute onset of chest pain. Computed tomography (CT) angiography in the emergency department reveals a type B aortic dissection, and she is brought to the surgical intensive care unit (ICU) for close hemodynamic monitoring and medical management of the dissection.
Which of the following factors most increased her risk for thoracic aortic dissection?
Correct Answer: D
GCA is an inflammatory vasculopathy affecting predominantly elderly patients, with a mean age of 70 to 80 years. 65% to 75% diagnoses are made in females. GCA affects medium and large arteries, specifically, those that have well-defined layers and in which vaso vasorum are present. It preferentially affects the external carotid arteries and its branches and thus typically presents with headache. The American College of Rheumatology (ACR) requires three of the following criteria for diagnosis of GCA:
Aortitis was previously thought to occur in 3% to 18% of patients with GCA, but these diagnoses were only made when aortic aneurysm formation or dissection became clinically apparent. Now, the true rate of aortic involvement is thought to be much higher, and thus regular screening of the aorta is recommended for patients with GCA to exclude aortitis and presence of an asymptomatic aneurysm. The screening modalities recommended are either the combination of chest radiograph, echocardiogram, and abdominal Doppler ultrasound or a CT scan of the chest and abdomen with intravenous contrast.
Although increasing age and hypertension are both risk factors for aortic dissection, the diagnosis of GCA is a much stronger risk factor for thoracic aneurysm formation and aortic dissection. In one population-based cohort study, patients with giant GCA were 17 times more likely to develop thoracic aortic aneurysm and 2.4 times more likely to develop isolated abdominal aortic aneurysm. Male gender, not female, increases risk for aortic dissection.
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A 65-year-old male presents with new onset thyrotoxicosis, and he is found to be in atrial fibrillation with rapid ventricular response and is hypotensive. He is currently being treated with propylthiouracil and steroids and awaiting total thyroidectomy for definitive therapy, while his cardiovascular status is optimized. During his hospitalization, he develops massive hemoptysis. He is intubated for airway protection and brought to the ICU where serial bronchoalveolar lavage (BAL) reveals progressively more hemorrhagic specimens with each aliquot. Laboratory analysis reveals a positive antineutrophil cytoplasmic antibody (ANCA) in a cytoplasmic pattern and a positive antiproteinase 3 (anti-PR3) antibody.
Which of the following medications is most associated with drug-induced ANCA vasculitis?
Correct Answer: C
This patient exhibits DAH, which occurs because of the accumulation of red blood cells into the alveolar space. It is diagnosed with BAL by observation of progressively more hemorrhagic aliquots. DAH generally presents with dyspnea, hemoptysis, chest infiltrates, and a fall in hemoglobin, though surprisingly, hemoptysis is absent in up to one-third of cases.
New diagnosis of DAH should prompt a diagnostic workup including serologies for the common forms of small-vessel vasculitis. Small-vessel vasculitis is defined as vasculitis that affects vessels smaller than arteries, such as arterioles, venules, and capillaries. ANCAs bind to antigens in neutrophil and monocyte lysosomes and occur in two staining patterns: cytoplasmic (c-ANCA) and perinuclear (p-ANCA). A positive ANCA is seen in granulomatosis with polyangiitis (GPA, formerly known as Wegener granulomatosis), eosinophilic granulomatosis with polyangiitis (EGPA, formerly known as Churg-Strauss syndrome), microscopic polyangiitis (MPA), and renal-limited ANCA vasculitis. Most patients with GPA have a c-ANCA pattern and antibodies to anti-PR3, whereas most patients with EGPAor MPAhave a p-ANCApattern and antibodies to anti-MPO.
Antithyroid drugs, including methimazole and propylthiouracil, are well-known to be associated with the development of ANCA-associated small-vessel vasculitis. Other drugs known to cause small-vessel vasculitis, with or without ANCA positivity, include hydralazine and levamisole (an agent found in adulterated cocaine).
Treatment for DAH secondary to drug-induced ANCA vasculitis includes withdrawal of the offending agent, high-dose corticosteroids, cyclophosphamide, and rituximab. Plasmapheresis is recommended in severe cases.
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A 56-year-old woman with a history of hypertension, hyperlipidemia, mixed connective tissue disease (MCTD), and hypothyroidism presents with respiratory failure secondary to influenza A and Staphylococcus aureus pneumonia. She is admitted to the ICU for invasive mechanical ventilation.
Titers of which of the following antibodies do you most expect to be positive?
There are five diffuse connective tissue disorders (DCTDs):
However, up to 25% of patients experience symptoms that may evolve from one disorder into another over time or have characteristics of several disorders at presentation, and thus are said to have an “overlap syndrome.” MCTD, also known as Sharp syndrome, is one such “overall syndrome” and shares clinical similarities with SLE, SS, and PM. Several sets of diagnostic criteria exist for MCTD, but the requirement for a positive Anti-U1-RNP antibody is universal among them. The Kasukawa criteria are one such, well-accepted, diagnostic criteria:
Aside from musculoskeletal manifestations (above), other clinical features of MCTD include pulmonary hypertension (affecting 10%-50% patients), interstitial lung disease (ILD) (affecting 47%-78% patients), oroesophageal involvement (affecting 64% patients), cardiovascular involvement (13%-65% patients), and renal involvement (5%-36% patients).
Among the other answer choices, anti-La is seen in primary Sjogren syndrome, anti-dsDNA is seen in SLE, and anti-PR3 and anti-MPO are seen in ANCAvasculitis.
A 47-year-old woman with MCTD presents from home with fever and dyspnea. In the emergency room, she is found to have hypoxemia with a room air saturation of 87% and a right upper lobe opacity on chest x-ray. Her oxygenation improves with supplemental oxygen and then she is transported to the CT scanner. There she acutely decompensated with worsened hypoxemia and hypotension prompting endotracheal intubation, presumably after a gastric aspiration event.
Which is the most common site of gastrointestinal involvement of MCTD?
Correct Answer: A
MCTD, also known as Sharp syndrome, is considered an “overall syndrome” and shares clinical similarities with SLE, SS, and PM. MCTD is characterized by positive anti-U1-RNP antibody. Aside from the musculoskeletal system, the cardiovascular system, gastrointestinal tract, lungs, hematologic system, renal system, and central nervous system may all be involved.
Among gastrointestinal manifestations, approximately 85% involve the esophagus. Of all patients with MCTD, 45% to 85% may experience esophageal dysmotility, which may be subclinical at the time of diagnosis. As in SS, esophageal studies including manometry or barium swallow may show reduced peristalsis of the lower third of the esophagus and deceased pressure of the lower esophageal sphincter. Whether esophageal dysmotility and subsequent aspiration of gastric contents in MCTD is related to the manifestation of ILD is an area of debate. In MCTD patients with normal esophageal motility, only 20% experience dyspnea, versus over 70% of those with moderately reduced esophageal peristalsis or aperistalsis.
Although esophageal involvement is the most common, MCTD may also affect nearly every component of the GI system, including delayed gastric emptying, slow intestinal transit, malabsorption, and colonic pseudodiverticula and colonic perforations.
A 68-year-old woman, who immigrated to the United States from Peru 7 years ago, with a history of rheumatoid arthritis (RA), maintained on adalimumab, presents to the emergency department with fever, arthralgias, dyspnea, and a productive cough. Physical examination is notable for distended abdomen with splenomegaly and ascites. Chest x-ray shows bilateral micronodular opacities, seen on subsequent chest CT scan with mediastinal lymphadenopathy and lymph node calcifications. Despite empiric antibiotic and antifungal coverage, her clinical condition worsened and was transferred to the ICU where intubation and mechanical ventilation instituted. Diagnostic bronchoscopy and paracentesis are performed. Rapid tuberculosis (TB) testing shows positivity in both the sputum and ascitic fluid samples, and both develop positive mycobacterial cultures at day 14.
Which of the following statements is true of her disseminated TB?
RA affects 5 in 1000 individuals worldwide, with 2 to 3× as many women as men affected and peak incidence in the sixth decade of life. Treatment of RA has evolved over the last 2 decades with the advent of biologic therapies targeted at stopping or substantially slowing the joint destruction seen in RA. Modern therapy for RA includes disease-modifying antirheumatic drugs (DMARDs), which refer to medications that reduce the signs and symptoms of RA, improve physical function, and inhibit progression of joint destruction. Methotrexate, together with steroid therapy, is the firstline DMARD. Biological agents are second-line therapy.
Biologic agents for RA include the TNFα-inhibitors (etanercept, infliximab, adalimumab, golimumab, certolizumab), IL-6 receptor antibodies (tocilizumab, sarilumab), the anti-CD20 antibody rituximab, and the anti-CD80/86 antibody abatacept. The TNFα antibodies place patients at increased risk for infection, reactivation of TB, drug-induced lupus, exacerbation of demyelinating diseases, nonmelanoma skin cancer, psoriaform skin changes, and injection or infusion site reactions. The risk for reactivation of TB is present for all biologic DMARDs except rituximab and perhaps abatacept. Thus, patients must be screened for latent TB before initiation of therapy and treated if positive. Despite this, false negatives are possible for both PPD and QuantiFERON-Gold tests; in addition, patients may develop new TB infection during therapy. The DMARDs targeted at the janus kinase (JAK) pathway, tofacitinib and baricitinib, increase risk for herpes zoster reactivation, not the anti-TNFα medications.
In patients maintained on anti-TNFα therapy, there is a fourfold increased risk of active TB infection, and in those who develop TB, extrapulmonary and disseminated TB are increased even when compared with other immunocompromised populations such as human immunodeficiency virus (HIV)–infected patients.
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