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CHAPTER 282: Systemic Rheumatic Diseases 1905 Radiographs show symmetric bone reabsorption medially, widen ing of the pubic symphysis, and sclerosis along the pubic rami. These changes may take several weeks to develop. MRI more clearly details the changes, and bone scans show evidence of the inflammatory process. 51-53 Diseases of Abnormal Calcification Myositis ossificans, or heterotrophic calcification, is the deposition of bone at a site where bone does not normally occur. The process is related to direct trauma, with the thigh and hip muscles frequently involved. Bleeding follows direct trauma to the muscle, and calcium deposits form inside the hematoma. A firm, palpable, painful mass will develop within 2 weeks and may persist for up to 1 year. Plain radiographs reveal an irregularly shaped mass around the joint or in the fascial planes ( Figure 281-22). The FIGURE 281-21. Radiograph of a 73-year-old man with Paget’s disease of the right proximal femur. Note the coarsening of the trabecular pattern with marked cortical thickening and narrowing of the joint space consistent with osteoarthritis secondary to pagetic deformity of the right femur. [Reproduced with permission from Fauci AS, Kasper DL, Braunwald E, et al: Harrison’s Principles of Internal Medicine, 17th ed. © 2008, McGraw-Hill, Inc., New York.] FIGURE 281-22. Myositis ossificans. This radiograph shows extraskeletal ossification of the medial proximal right thigh (immediately inferior to the head of the femur), approxi mately 3 weeks after a severe contusion to that area. [Reproduced with permission from Simon RR, Sherman SC, Koenigsknecht SJ: Emergency Orthopedics: The Extremities, 5th ed. © 2007, McGraw-Hill, Inc., New York.] appearance may be confused with a primary neoplasm, such as osteosarcoma or periosteal osteogenic sarcoma. Range of motion in the muscle or joint is limited due to pain or physical presence of the mass. Radicular pain from nerve irritation may also be present. Operative removal of the deposition may be required. Calcifying peritendinitis and bursitis are also traumatic in origin but are relatively uncommon. The trochanteric bursa of the hip is frequently affected. Radiographs reveal a thin, poorly marginated white line that is separated from the cortex of the hip. CORE TREATMENT Treatment for the majority of inflammatory and overuse syndromes consists of NSAIDs, rest, heat, and time as the basis of conservative treatment (Table 281-5). “Rest” does not require full immobilization, which can lead to muscle atrophy and delayed return to normal func tion. Full knee immobilization, which is commonly prescribed from the ED, should therefore be used sparingly in most of these conditions. Appropriate rest is followed by gradual resumption of activities, physical therapy, and strengthening activities where appropriate. Steroids may occasionally be required, and steroid injections into the more readily accessible bursa are useful when it is clear that no infection exists but can be detrimental when infection is present. It is critical to avoid ste roid injections into tendons, because steroids may weaken the tendon and lead to rupture. Athletes are best served by referral to a sports medicine specialist or an orthopedist. Advanced therapies such as stem cell or platelet-rich plasma injections continue to develop for a variety of conditions. 55-60 REFERENCES The complete reference list is available online at www.TintinalliEM.com.
and lead to rupture. Athletes are best served by referral to a sports medicine specialist or an orthopedist. Advanced therapies such as stem cell or platelet-rich plasma injections continue to develop for a variety of conditions. 55-60 REFERENCES The complete reference list is available online at www.TintinalliEM.com. TABLE 281-5 Treatment Caveats • Do not inject steroids in areas where infection is a concern, or where they may accidentally be injected into tendon sheaths and contribute to tendon rupture. • Use caution in the examination of the immunocompromised patient, because signs of infection may be subtle or altered. • Injuries in athletes should be referred to a sports medicine specialist to optimize therapy and decrease time to return to maximum activity levels. Systemic Rheumatic Diseases Rachel M. Wolfe Andrew C. Seymore R. Darrell Nelson INTRODUCTION Systemic rheumatic diseases are chronic, inflammatory autoimmune disorders, such as osteoarthritis, rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis (scleroderma). ED patients with systemic rheumatic diseases have complex clinical and pharmacologic histories and multi–organ system pathology. Many extra-articular manifestations of rheumatic diseases can result in serious morbidity or mor tality if not recognized and properly managed. 1,2 This chapter discusses rheumatologic emergencies from an organ system perspective. It will review both rheumatologic emergencies as well as care for the rheuma tologic patient in the ED. Table 282-1 categorizes emergencies associ ated with systemic rheumatic diseases. Although the chapter should be CHAPTER Tintinalli_Sec23_p1881-1932.indd 1905 8/2/19 3:15 PM
rgencies from an organ system perspective. It will review both rheumatologic emergencies as well as care for the rheuma tologic patient in the ED. Table 282-1 categorizes emergencies associ ated with systemic rheumatic diseases. Although the chapter should be CHAPTER Tintinalli_Sec23_p1881-1932.indd 1905 8/2/19 3:15 PM 1906 SECTION 23: Musculoskeletal Disorders reviewed in its entirety, high-yield clinical pearls can be found at the end of the chapter in Table 282-8. CLINICAL FEATURES AND DIAGNOSIS Table 282-2 lists typical clinical manifestations and complications spe cific to rheumatic diseases. The clinical descriptors may allow suspicion for a systemic rheumatic disease in a previously undiagnosed patient; however, the diagnosis cannot be confirmed during an ED visit. The diagnostic criteria and testing sequence, which are usually completed in the outpatient setting, are beyond the scope of this chapter. The need to admit a patient with a known or suspected systemic rheumatic ill ness depends on the severity of the patient’s presentation. In systemic rheumatic diseases, infection is the leading cause for intensive care unit admission followed by rheumatic disease flare. 3 The intensive care unit admission may be the site of initial diagnosis in 20% of those with systemic rheumatic disease. Rheumatoid arthritis is the most common rheumatic disease seen in intensive care unit patients (also the most common rheumatic disease), followed in decreasing frequency by sys temic lupus erythematosus and systemic sclerosis. AIRWAY EMERGENCIES Critical airway obstruction may develop at the level of the larynx, sub glottic region, or trachea. CRICOARYTENOID JOINT ARTHRITIS In patients with rheumatoid arthritis and relapsing polychondritis, arthritis or edema of the cricoarytenoid joints can lead to acute upper airway obstruction. 1,4 In addition, secondary infections such as bacte rial epiglottitis or tracheitis can quickly compromise the airway. Signs and symptoms of cricoarytenoid arthritis are throat pain, tenderness over cartilaginous structures (aggravated by swallowing or speak ing), foreign body sensation or fullness in the throat, voice changes or hoarseness, and in more severe cases, dyspnea, cough, or stridor. Pain from cricoarytenoid arthritis is sometimes referred to the ear or to the neck. CT and fiberoptic laryngoscopy can evaluate the cricoarytenoid joint. Initial treatment consists of systemic high-dose corticosteroids and racemic epinephrine inhalation, although tracheostomy may be required. 1,5 TRACHEOMALACIA Relapsing polychondritis can cause inflammation, destruction, and collapse of tracheobronchial cartilage, resulting in airway obstruction. Regions of segmental collapse due to tracheomalacia or refractory stenosis may be resected or treated with stents. The use of noninvasive TABLE 282-1 Categories of Emergencies in Patients With Systemic Rheumatic Diseases Category Clinical Manifestations Disease exacerbation Flare-up of preexisting systemic rheumatic disease Complication Known complication of an acute systemic rheumatic dis ease (i.e., pulmonary hemorrhage, pericarditis, respiratory, or renal impairment) Infection Infection complicated by immunosuppressive therapy Comorbidity exacerbation Worsening or onset of a serious illness that is not a direct manifestation of the systemic rheumatic disease Adverse drug reaction Reaction to a systemic rheumatic disease drug treatment TABLE 282-2 Common Features and Complications of Systemic Rheumatic Diseases Disorder Common and Characteristic Clinical Features Complications Antiphospholipid syndrome Multiple and recurrent venous and arterial thromboses, recurrent early abortions.
rug reaction Reaction to a systemic rheumatic disease drug treatment TABLE 282-2 Common Features and Complications of Systemic Rheumatic Diseases Disorder Common and Characteristic Clinical Features Complications Antiphospholipid syndrome Multiple and recurrent venous and arterial thromboses, recurrent early abortions. Secondary form is associated with systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis, and Sjögren’s syndrome. Thrombophlebitis and deep vein thrombosis, thrombocytopenia, hemolytic anemia, microangiopathic hemolytic anemia, livedo reticularis, stroke, transient ischemic attack, eye vascular complications. Coronary, renal, mesenteric, and cerebral vascular occlusion. ARDS, pulmonary embolism, ischemic complications of vascular occlusion, severe anemia, vision loss, catastrophic antiphospholipid syndrome. Ankylosing spondylitis Chronic inflammatory disease of the axial skeleton, with progressive stiffness of the spine. Young adults (peak at 20 and 30 years old). Back pain (improves with exercise, morning stiffness lasting >1 hour); buttock, hip, or shoulder pain; systemic complaints (fever, malaise, fatigue, weight loss, myalgias); uveitis and restrictive pulmonary failure due to costovertebral rigidity; ILD; fracture of the ankylosed spine; asymptomatic ileal and colonic mucosal ulcerations. Secondary amyloidosis. Acute spinal cord or nerve compression, subluxation of the atlantoaxial joint, spine fracture from minimal or no trauma, aortic regurgitation. Adult Still’s disease Inflammatory disorder (similar to systemic-onset juvenile rheumatoid arthritis). Systemic complaints (fever, malaise, fatigue, weight loss, myalgia), arthritis, evanescent (salmon-colored) rash, pharyngitis, lymphadenopathy, splenomegaly, anemia, thrombocytopenia. Pericarditis, myocarditis, pleurisy. ARDS, arrhythmias, heart failure, fulminant hepatic failure, red cell aplasia, disseminated intravascular coagulation, microangiopathic hemolytic anemia. Behçet’s disease Chronic, relapsing, inflammatory disease. Systemic vasculitis involving arteries and veins of all sizes (carotid, pulmonary, aortic, and inferior extremity vessels are most commonly involved, with aneurysm, dissection, rupture, or thrombosis). Systemic complaints (fever, malaise, fatigue, weight loss, myalgia); recurrent painful skin and mucosal lesions (oral and genital ulcerations); asymmetric, nondeforming arthritis of the medium and large joints; thrombophlebitis and deep vein thrombosis; ocular complications. Neuropsychiatric manifestations. Pericarditis, myocarditis. Hypopyon, retinal vasculitis, optic neuritis, eye vascular complication. Dural sinus thrombosis, aseptic meningitis, and encephalitis. Arrhythmias. Superior and inferior vena cava syn drome. Abdominal aorta or pulmonary artery emergencies. Bowel perforation. Eosinophilic granulomatosis with polyangiitis (formally, Churg-Strauss syndrome) Vasculitis with a multisystemic involvement. Systemic complaints (fever, malaise, fatigue, weight loss, myalgia), myalgia, allergic rhinitis, nasal obstruction, recurrent sinusitis, asthma, and periph eral blood eosinophilia. Systemic hypertension, pericarditis, abdominal pain, peripheral symmetric neuropathy; skin lesions and rash. Heart failure, acute myocardial infarction, acute and constrictive pericarditis, mononeuritis multiplex, transverse myelitis. Dermatomyositis/polymyositis Idiopathic inflammatory myopathies. Symmetric proximal muscle weakness, myalgia, and muscle tenderness. Elevated serum creatine kinase. Systemic complaints (fever, malaise, fatigue, weight loss), Raynaud phenomenon, nonerosive inflammatory polyarthritis, esophageal dysfunction, ILD, aspiration lung infections. ARDS.
is Idiopathic inflammatory myopathies. Symmetric proximal muscle weakness, myalgia, and muscle tenderness. Elevated serum creatine kinase. Systemic complaints (fever, malaise, fatigue, weight loss), Raynaud phenomenon, nonerosive inflammatory polyarthritis, esophageal dysfunction, ILD, aspiration lung infections. ARDS. Respiratory failure and arrest due to diaphragmatic or chest wall muscle weakness, alveolar hemorrhage, and ILD. Heart failure, arrhythmias, and conduction disturbances. (Continued) Tintinalli_Sec23_p1881-1932.indd 1906 8/2/19 3:15 PM
is Idiopathic inflammatory myopathies. Symmetric proximal muscle weakness, myalgia, and muscle tenderness. Elevated serum creatine kinase. Systemic complaints (fever, malaise, fatigue, weight loss), Raynaud phenomenon, nonerosive inflammatory polyarthritis, esophageal dysfunction, ILD, aspiration lung infections. ARDS. Respiratory failure and arrest due to diaphragmatic or chest wall muscle weakness, alveolar hemorrhage, and ILD. Heart failure, arrhythmias, and conduction disturbances. (Continued) Tintinalli_Sec23_p1881-1932.indd 1906 8/2/19 3:15 PM CHAPTER 282: Systemic Rheumatic Diseases 1907 TABLE 282-2 Common Features and Complications of Systemic Rheumatic Diseases Disorder Common and Characteristic Clinical Features Complications Giant cell arteritis (temporal arteritis) Chronic vasculitis of large-sized vessels. Elderly (mean age at diagnosis, 70 y old). Associated with polymyalgia rheumatica in 40% of cases. Localized headache of new onset, tenderness of the temporal artery, and biopsy revealing a necrotizing arteritis. Temporal artery may be normal on clinical examination. Systemic complaints, jaw claudication, eye complaints, and visual loss. Aortic regurgitation and aortic arch syndrome. Neurologic complications due to carotid and vertebrobasilar vasculitis. Ischemic optic neuropathy, eye vessel occlusion. Aortitis (especially the thoracic tract) and aortic emergencies. Stroke. Henoch-Schönlein purpura Systemic vasculitis associated with immunoglobulin A deposition, generally in children. Fre quently, acute presentation follows an upper respiratory infection. Palpable purpura (in patients with neither thrombocytopenia nor coagulopathy), arthritis/arthralgia, abdominal pain, and renal impairment (adult), ILD. Respiratory failure and alveolar hemorrhage. GI hemorrhage, bowel ischemia or perforation, acute pancreatitis, intussusception (children). Acute scrotum. Microscopic polyangiitis Small-vessel systemic vasculitis, characterized by rapidly progressive glomerulonephritis and pul monary involvement. Lung complications differentiate microscopic polyangiitis from polyarteritis nodosa. Systemic complaints (fever, malaise, fatigue, weight loss, myalgia), arthralgias, skin lesions, hemoptysis, abdominal pain, renal impairment, systemic hypertension. Rapidly progressive glomerulonephritis, severe lung hemorrhage, GI bleeding. Polyarteritis nodosa Systemic necrotizing vasculitis of the medium-sized muscular arteries. Systemic complaints (fever, malaise, fatigue, weight loss, myalgia), arthralgias, skin lesions, abdominal pain, renal impair ment, systemic hypertension, peripheral mononeuropathy typically with both motor and sensory deficits, eye complications, leukocytosis, and normochromic anemia. Acute scrotum, ischemic and hemorrhagic stroke, ACS, heart failure, peripheral artery ischemia, mesenteric ischemia and bowel perforation, GI bleeding, acute pancreatitis, malignant hypertension. Relapsing polychondritis Immune-mediated condition. Ears (violaceous and erythematous auricula), nose (saddle nose deformity), and other cartilaginous structures inflammation (respiratory tract). Sternoclavicular, costochondral, and manubriosternal arthritis; upper airway involvement; aortic or mitral valvular regurgitation; pericarditis; renal impairment; peripheral neuropathies; ocular complications. Airway obstruction. Acute renal failure, aortitis and aortic emergencies, heart block, ACS, scle ritis, peripheral ulcerative keratitis. Rheumatoid arthritis Chronic, systemic, inflammatory disorder. Symmetric and potentially destructive arthritis. Systemic symptoms (fever, malaise, fatigue, weight loss, myalgia), skin lesions, splenomegaly. Cervical spine involvement, pleuritis, ILD, pericarditis, myocarditis, and aortitis. Cricoarytenoid arthritis with potential for airway obstruction, ocular involvement. Peripheral artery disease, Sjögren’s syndrome, vasculitis. Anemia, leukopenia, thrombocytosis, and Felty’s syndrome.
lgia), skin lesions, splenomegaly. Cervical spine involvement, pleuritis, ILD, pericarditis, myocarditis, and aortitis. Cricoarytenoid arthritis with potential for airway obstruction, ocular involvement. Peripheral artery disease, Sjögren’s syndrome, vasculitis. Anemia, leukopenia, thrombocytosis, and Felty’s syndrome. Increased risk of lymphoproliferative diseases, particularly non-Hodgkin’s lymphoma. Airway obstruction, obliterative bronchiolitis, acute respiratory failure. Acute coronary syndrome, heart failure, thoracic aorta dissection, arrhythmias and conduction disturbances, subluxation of the atlantoaxial joints, bowel ischemia and perforation. Septic arthritis. Scleritis. Systemic lupus erythematosus Systemic autoimmune disease, characterized by relapses and remissions and affecting virtually every organ. Systemic complaints (fever, malaise, fatigue, weight loss, myalgia), symmetric and polyarticular inflammatory arthritis (small joints of the hands, wrists, and knees), butterfly rash, oral and/or nasal ulcers, Raynaud’s phenomenon. Neuropsychiatric manifestations, pleurisy, ILD, and pulmonary hypertension. Libman-Sacks endocarditis, pericarditis, myocarditis, endocarditis. Renal impairment (nephritis), leukopenia, mild anemia, and thrombocytopenia. Antiphospholipid syndrome. Ocular complications. Airway obstruction, ARDS, respiratory failure and arrest, alveolar hemorrhage, ACS, cardiac tamponade, heart failure, arrhythmias, pulmonary embolism, stroke, acute renal failure, Guillain-Barré–like syndrome, transverse myelitis, seizures. Bowel ischemia and perforation, GI bleeding, acute pancreatitis. Hemolytic anemia, thrombotic microangiopathic hemolytic anemia. Sjögren’s syndrome Autoimmune disease. May be primary; secondary form is mostly associated with rheumatoid arthritis, systemic lupus erythematosus. Xerophthalmia and xerostomia, systemic symptoms, arthralgia, skin lesions, Raynaud’s phenomenon. ILD, pulmonary hypertension, pericarditis, neuropsychiatric manifestations, peripheral neuropathy, hepatic abnormalities, renal impairment, increased risk of non-Hodgkin’s lymphoma. Hypokalemic respiratory arrest. Heart block, pulmonary embolism, ischemic stroke, transverse myelitis, optic neuritis, renal tubular acidosis, acute pancreatitis. Systemic sclerosis (scleroderma) Inappropriate and excessive accumulation of collagen and matrix in a variety of tissue; widespread vascular lesions with endothelial dysfunction, vascular spasm, thickening of the vascular wall and narrowing of the vascular lumen. Systemic complaints (fever, malaise, fatigue, weight loss, myalgia), skin lesions (fingers, hands, and face), carpal tunnel syndrome, Raynaud’s phenomenon. ILD, renal impairment, GI dysmotility, gastroesophageal reflux (aspiration pneumonitis), chronic esophagitis, and stricture formation. Vascular ectasia in the stomach (“watermelon stomach”). Scleroderma renal crisis. Respiratory failure, ARDS, aspiration pneumonitis, pulmonary hypertension, alveolar hemorrhage, heart failure, arrhythmias, and conduction disturbances. Ischemia and gangrene of the digits. Takayasu’s arteritis Chronic vasculitis, young women, predominantly Asians. Systemic complaints (fever, malaise, fatigue, weight loss, myalgia), arthralgias, skin lesions, abdominal pain, and diarrhea. Aorta and its primary branches, and pulmonary artery involvement. Neurologic manifestations, syncope, sub clavian steal syndrome, extremity ischemia. Renovascular hypertension. Normochromic normocytic anemia. ACS, bowel ischemia and perforation, GI bleed ing, stroke. Granulomatosis with polyangiitis (Wegener’s) Multiple organ system vasculitis and necrotizing granulomas.
involvement. Neurologic manifestations, syncope, sub clavian steal syndrome, extremity ischemia. Renovascular hypertension. Normochromic normocytic anemia. ACS, bowel ischemia and perforation, GI bleed ing, stroke. Granulomatosis with polyangiitis (Wegener’s) Multiple organ system vasculitis and necrotizing granulomas. Upper and lower respiratory tract manifestations—nose, oral cavity, upper trachea, external and middle ear, and orbit inflamma tions. Constitutional symptoms, arthralgias, glomerulonephritis, and small-vessel vasculitis (scleritis and episcleritis, palpable purpura or cutaneous nodules, peripheral neuropathy, deaf ness). Systemic hypertension. Pericarditis, myocarditis. Renal impairment. Anemia, leukocytosis, and thrombocytosis. Airway obstruction, subglottic stenosis, diffuse alveolar hemorrhage. ACS, arrhythmias. Rapidly progressive glomerulonephritis. Abbreviations: ACS = acute coronary syndrome; ARDS = adult respiratory distress syndrome; ILD = interstitial lung disease. (Continued) Tintinalli_Sec23_p1881-1932.indd 1907 8/2/19 3:15 PM
sis. Airway obstruction, subglottic stenosis, diffuse alveolar hemorrhage. ACS, arrhythmias. Rapidly progressive glomerulonephritis. Abbreviations: ACS = acute coronary syndrome; ARDS = adult respiratory distress syndrome; ILD = interstitial lung disease. (Continued) Tintinalli_Sec23_p1881-1932.indd 1907 8/2/19 3:15 PM 1908 SECTION 23: Musculoskeletal Disorders positive-pressure ventilation may help to prevent airway collapse. Car tilaginous destruction results in a small glottis, so when intubation is required, use a smaller endotracheal tube than normal. INTUBATION IN PATIENTS WITH SYSTEMIC RHEUMATIC DISEASES Endotracheal intubation is considered “difficult” in patients with systemic rheumatic diseases because of airway-related aspects of the disease. 1,5 Anticipate the need for adjunctive airway techniques, consider video laryngoscopy or fiberoptic intubation, and prepare to perform surgical cricothyrotomy. When the airway is patent but intubation is anticipated, and the patient can be safely transferred, it may be prefer able to go to the operating room for a “double setup, ” with preparation for a formal tracheostomy if oral intubation is unsuccessful. Many rheumatic diseases can complicate the mechanics of intubation including rheumatoid arthritis, ankylosing spondylitis, and sclero derma. Patients with rheumatoid arthritis and ankylosing spondylitis can develop temporomandibular joint dysfunction with reduced mouth opening. Skin tightening from scleroderma can significantly decrease oral aperture. In both rheumatoid arthritis and ankylosing spondylitis, flexion and hyperextension can exacerbate atlantoaxial instability and C1-C2 sub luxation and increase the risk of fracture. 1 Atlantoaxial instability and C1-C2 subluxation are prevalent in long-standing, seropositive rheumatoid arthritis (especially if poorly controlled) and should be taken into account with intubation. Patients with cervical ankylosis are at high risk for cervical fractures (even after minor trauma). Subglottic stenosis or acute upper airway obstruction with an inability to clear tracheobronchial secretions may be observed in and even be a presenting sign of granulomatosis with polyangiitis (Wegener’s). Sub glottic stenosis often requires surgical intervention. PULMONARY EMERGENCIES Lung involvement, due to the underlying disease itself or secondary to infection, is a frequent cause of major morbidity and death, particularly in systemic sclerosis, rheumatoid arthritis, systemic lupus erythe matosus, vasculitis, and polymyositis/dermatomyositis. 1,2,5 Pulmonary complications of systemic rheumatic disease manifest primarily as interstitial lung disease and vascular disease. 5,6 Due to chronic lung injury, interstitial pulmonary fibrosis, or pulmonary hypertension, even mild infections in patients with systemic rheumatic disease can lead to respiratory failure. 5-7 Respiratory arrest has been reported in systemic lupus erythematosus and dermatomyositis/polymyositis patients due to phrenic nerve involvement, in rheumatoid arthritis patients due to cervicomedullary compression associated with rheumatoid atlantoaxial dislocation, and in Sjögren’s syndrome patients due to hypokalemic paralysis secondary to distal renal tubular acidosis. Symptoms can develop due to chronic manifestations of the underlying disease (e.g., interstitial lung disease), or new symptoms can develop due to an acute complication such as pneumonia or alveolar hemorrhage. Several complications outside the pulmonary parenchyma cause respiratory symptoms such as involvement of the joints of the thoracic cage (in ankylosing spondylitis), pleural effusion, respiratory muscle inflamma tory disease (polymyositis/dermatomyositis), cardiac involvement, and anemia.
umonia or alveolar hemorrhage. Several complications outside the pulmonary parenchyma cause respiratory symptoms such as involvement of the joints of the thoracic cage (in ankylosing spondylitis), pleural effusion, respiratory muscle inflamma tory disease (polymyositis/dermatomyositis), cardiac involvement, and anemia. 5,6 Of note, respiratory muscles can be involved in myositis, and if there is concern, serial measurements of negative inspiratory force can provide information about impending respiratory decline. 5 Pulmonary embolism risk is higher in systemic rheumatologic diseases. 8,9 Lastly, immunosuppressive therapies themselves can cause pulmonary complications (e.g., methotrexate can cause pulmonary fibrosis) as well increase the risk of both typical and atypical infections. 6,10 ALVEOLAR HEMORRHAGE Alveolar hemorrhage requiring hospital admission has a hospital mortality rate of 25%. 11 It is a complication of systemic lupus erythematosus, antiphospholipid syndrome, systemic vasculitis (granulomatosis with polyangiitis [Wegener’s], microscopic polyangiitis, others), Behçet’s disease, and very rarely, systemic sclerosis. Early recognition and aggressive management are critical for improved outcome.11 Delay in treatment, age >60 years old, end-stage renal failure, and cardiovascular comorbidity worsen prognosis. 11 Patients with alveolar hemorrhage complain of acute shortness of breath, fever, and cough. Symptom onset is usually abrupt, with a progression to respiratory failure requiring mechanical ventilation. The classical triad of hemoptysis, pulmonary infiltrates on chest radiograph, and rapid decrease in hemoglobin level supports the diagnosis, but the triad is frequently not present. 12,13 Most commonly, alveolar hemorrhage is mistakenly diagnosed as “atypical” pneumonia. Thus, a diagnosis of atypical pneumonia should raise the consideration of alveolar hemorrhage, especially if a new anemia is present. 12 If symptoms are accompanied by high fever, it is difficult to distinguish between alveolar hemorrhage and infectious pneumonia. The distinction is of utmost importance, because the therapeutic options are exactly the opposite (immunosuppressant vs. antibiotics). Emergent bronchoscopy with bronchoalveolar lavage can confirm the diagnosis but is done after admission. Treatment is directed to the underlying condition and includes high-dose glucocorticoids (up to 1 gram of methylprednisolone daily) and cyclophosphamide. 14,15 Local vessel embolization and plasmapheresis are used, but benefit is less clear.15 INTERSTITIAL LUNG DISEASE Interstitial lung disease is characterized by infiltration of the pulmonary interstitium by inflammatory cells and matrix, leading to fibrosis, pul monary hypertension, and respiratory insufficiency. Rheumatoid arthritis, systemic sclerosis, and polymyositis/dermatomyositis are commonly associated with interstitial lung disease. 5,16 Interstitial lung disease may be asymptomatic, may produce slowly progressive symptoms (cough and dyspnea), or, rarely, can cause acute respiratory failure. Treatment in the ED is ventilatory support, with oxygen, noninvasive ventilation, and intubation as needed. 16 Immunomodulators, such as rituximab, are given at the discretion of the rheumatology consultant.17 PULMONARY HYPERTENSION Pulmonary arterial hypertension can be a complication of any rheumatic disease with associated pulmonary fibrosis and interstitial lung disease but is most common in systemic sclerosis and systemic lupus erythematosus. 7 Acute or chronic pulmonary embolism may also lead to pulmonary arterial hypertension.
HYPERTENSION Pulmonary arterial hypertension can be a complication of any rheumatic disease with associated pulmonary fibrosis and interstitial lung disease but is most common in systemic sclerosis and systemic lupus erythematosus. 7 Acute or chronic pulmonary embolism may also lead to pulmonary arterial hypertension. Clinical symptoms reported by patients with pulmonary arterial hypertension range from cough or mild shortness of breath to severe dyspnea, cardiac arrhythmias, chest pain, and right ventricular failure. Management includes optimization of fluid volume and treatment of right heart failure. 18 For further discussion, see Chapter 58, “Pulmonary Hypertension. ” CARDIOVASCULAR EMERGENCIES Cardiac disease develops through several pathophysiologic mechanisms, accounting for different manifestations such as inflammation, fibrosis, infiltration, vasculitis, thromboembolism, and accelerated coronary atherosclerosis. 19 Table 282-3 provides a review of cardiac disorders in patients with systemic rheumatic diseases.20-24 ACUTE CORONARY SYNDROMES Many systemic rheumatic diseases promote accelerated coronary atherosclerosis and have an increased rate of cardiovascular morbidity and mortality. 19-23 The relative risk is most pronounced in systemic lupus erythematosus and rheumatoid arthritis. 20,21 The risk of myocardial infarction in young, premenopausal women with lupus is between 2- and 10-fold compared with women without lupus and is a major cause of mortality, especially in younger patients. 20 Surprisingly, traditional risk factors do not fully explain the rates of cardiovascular disease in these patient populations. 22 It is hypothesized to be driven by the underlying disease, proinflammatory state, and potentially the medications used to treat the disease (e.g., glucocorticoids). The risk of cardiovascular disease in inflammatory systemic rheu matic diseases equals that of type 2 diabetes, so clinically, it is useful Tintinalli_Sec23_p1881-1932.indd 1908 8/2/19 3:15 PM
e underlying disease, proinflammatory state, and potentially the medications used to treat the disease (e.g., glucocorticoids). The risk of cardiovascular disease in inflammatory systemic rheu matic diseases equals that of type 2 diabetes, so clinically, it is useful Tintinalli_Sec23_p1881-1932.indd 1908 8/2/19 3:15 PM CHAPTER 282: Systemic Rheumatic Diseases 1909 to consider systemic rheumatic disease a “risk factor” for coronary atherosclerosis.25 Consequently, consider acute coronary syndrome in younger patients without traditional cardiovascular risk factors who have rheumatic diseases, particularly systemic lupus erythematosus and rheumatoid arthritis. Medical management of acute coronary syndrome is the same as in the normal population. ACUTE HEART FAILURE Acute heart failure may develop as a consequence of a myocardial dis ease (ischemia, cardiomyopathy, myocarditis, fibrosis), pericardial dis ease (tamponade or constrictive), valvular diseases (acute regurgitation), and/or conduction or rhythm disturbance. 19,20,24 Acute management of decompensated heart failure does not differ from the normal popula tion, except when a flare of the underlying disease is responsible. In systemic sclerosis, diastolic dysfunction, malignant hypertension during a scleroderma renal crisis, and decompensated pulmonary hypertension are important causes of acute heart failure. CARDIAC ARRHYTHMIAS Rhythm and conduction disturbances are common, especially in rheumatoid arthritis, systemic sclerosis, sarcoidosis, systemic lupus erythematosus, and polymyositis/dermatomyositis. The pathophysi ologic basis for these disorders is complex, involving reentry pathways, fibrosis, altered automaticity, conduction system injury, primary and/or secondary myocardial injury, and side effects of treatment. Population studies demonstrate a 40% higher risk for atrial fibrillation in patients with rheumatoid arthritis. 24,26 Arrhythmias and sudden cardiac death in systemic rheumatic disease have a higher incidence compared with the normal population. 24,26 Ventricular arrhythmias are a risk for sudden cardiac death, especially in patients with systemic sclerosis.24 MALIGNANT HYPERTENSION Systemic hypertension may be a clinical manifestation of renal injuries or an adverse effect of disease treatment. Severe malignant hypertension is a complication of systemic sclerosis (usually observed during a “renal crisis”), but it can be also observed in catastrophic antiphospholipid syndrome, polyarteritis nodosa, and a few other rheumatic diseases. VASCULAR AND VALVULAR DISEASE Valvular heart disease is an extra-articular manifestation of spondylo arthropathies, particularly ankylosing spondylitis. Fibrotic changes of the aortic valve cusps lead to valvular insufficiency of the aortic and/ or mitral valves. Arterial lesions can be aneurysmal (frequently compli cated by fatal rupture) or, less commonly, occlusive. Aortitis may lead to aortic aneurysms in patients with giant cell arteritis (temporal arteritis), Takayasu’s arteritis, and Behçet’s disease, and aneurysms may rupture or dissect. In giant cell arteritis, great vessel involvement due to arteritis can result in aortic valve incompetence and aortic aneurysm as a late complication of the disease. Takayasu’s arteritis involves the larger vessels, which can include pulmonary artery inflammation (resulting in hemoptysis, aneurysm, thrombosis, hemorrhage, and pulmonary infarction), as well as arterial narrowing and/or aortitis, which can produce neurologic symptoms or syncope related to the subclavian steal syndrome. Because Takayasu’s arteritis is found in predominantly young women, these would be uncommon symptoms or manifestations as compared to their healthy peers.
and pulmonary infarction), as well as arterial narrowing and/or aortitis, which can produce neurologic symptoms or syncope related to the subclavian steal syndrome. Because Takayasu’s arteritis is found in predominantly young women, these would be uncommon symptoms or manifestations as compared to their healthy peers. Libman-Sack’s endocarditis (sterile verrucous lesions) can produce valvular abnormalities seen in both antiphospholipid antibody syn drome and systemic lupus erythematosus. 27 Valvular lesions are often asymptomatic, although emboli can produce systemic symptoms (stroke, renal infarction). In both diseases, valvular destruction with resultant regurgitation are possible, with mitral valve involvement most common. Additionally, valves with underlying pathology are often fertile areas for infective endocarditis to settle. THROMBOEMBOLISM Superficial thrombophlebitis and deep vein thrombosis are common in Behçet’s disease. Thrombosis is related to vascular inflammation and more commonly venous than arterial. 28 After the veins of the lower extremities, other affected veins are the inferior and superior vena cava and hepatic veins (Budd-Chiari). Immunosuppression is TABLE 282-3 Cardiovascular Emergencies in Patients with Systemic Rheumatic Diseases
is related to vascular inflammation and more commonly venous than arterial. 28 After the veins of the lower extremities, other affected veins are the inferior and superior vena cava and hepatic veins (Budd-Chiari). Immunosuppression is TABLE 282-3 Cardiovascular Emergencies in Patients with Systemic Rheumatic Diseases ACS, AMI Acute Pericarditis Aortic Emergencies Aortic Valve Regurgitation Arrhythmias, Heart Blocks Aneurysm Budd-Chiari Syndrome Cardiac Tamponade DVT and PE Endocarditis Heart Failure Malignant Hypertension Myocarditis Peripheral Artery Ischemia Pulmonary Artery Injury Subclavian Steal Syndrome Sudden Cardiac Death Superior Vena Cava Syndrome Ankylosing spondylitis X Adult Still’s disease X X X Antiphospholipid antibody syndrome X X X X X X X X Behçet’s disease X X X X X X X X X X X X Churg-Strauss syndrome X X X X Dermatomyositis/polymyositis X X X X Giant cell (temporal) arteritis X X X Granulomatosis with polyangiitis (Wegener’s) X X X X Polyarteritis nodosa X X X X X Rheumatoid arthritis X X X X X X X X X Systemic lupus erythematosus X X X X X X X X X X Sjögren’s syndrome X X Systemic sclerosis X X X X X X X X Takayasu’s arteritis X X X X X X X X Abbreviations: ACS = acute coronary syndrome; AMI = acute myocardial infarction; DVT = deep vein thrombosis; PE = pulmonary embolism. Tintinalli_Sec23_p1881-1932.indd 1909 8/2/19 3:15 PM
jögren’s syndrome X X Systemic sclerosis X X X X X X X X Takayasu’s arteritis X X X X X X X X Abbreviations: ACS = acute coronary syndrome; AMI = acute myocardial infarction; DVT = deep vein thrombosis; PE = pulmonary embolism. Tintinalli_Sec23_p1881-1932.indd 1909 8/2/19 3:15 PM 1910 SECTION 23: Musculoskeletal Disorders the mainstay of treatment of thromboembolism in Behçet’s disease, 29 with much controversy over whether ongoing anticoagulation is indicated.30,31 Acute cases should be treated at diagnosis with methylprednisolone 1 gram. 29,32 When considering an anticoagulant, consider potential for active bleeding and discuss with a rheumatology consultant prior to initiation. Thromboembolic disease may also be observed as a complication of systemic lupus erythematosus and the antiphospholipid syndrome; for treatment recommendations, see later discussion. Vessel thrombosis can be venous and/or arterial, affect any vessel, and be recurrent and bilateral. Peripheral gangrene, acute coronary syndrome, renal artery thrombosis, sagittal sinus thrombosis, transient ischemic attack, and Budd-Chiari syndrome due to hepatic vein thrombosis are possible examples of thromboembolism from rheumatic disease. CATASTROPHIC ANTIPHOSPHOLIPID SYNDROME This uncommon vaso-occlusive process leads to multiorgan failure and is often associated with systemic lupus erythematosus, but it may be observed in other systemic rheumatic diseases. 33,34 Multiple simultaneous venous and/or arterial occlusive thromboses with resultant multiorgan failure develop suddenly and progress rapidly over days. In half of the cases, a precipitating factor may be identified (e.g., infection, surgery, trauma, exogenous estrogen exposure). The kidney is the primary organ involved (acute kidney injury), followed by the lungs (adult respiratory distress syndrome, embolism), CNS (stroke, seizures, venous occlu sion), heart (acute myocardial infarction and heart failure), and skin (necrosis). Livedo reticularis (lacelike purplish discoloration of the lower extremities) and thrombocytopenia are important diagnostic findings (a decrease in platelet count is observed in 60% of cases), and occasionally, laboratory features of disseminated intravascular coagulation may be present. This dramatic clinical scenario is frequently fatal, with a reported mortality rate approaching 50% despite therapy. Initial treatment is heparin and high-dose glucocorticoids (methylprednisolone 1 gram) along with treatment of the underlying triggering condition. 35 Unfractionated heparin followed by transition to warfarin is the recommended anticoagulant regimen of choice because of the anti-inflammatory properties of unfractionated heparin and the safety and efficacy demonstrated in this population. 33 Other modalities of treatment to consider include plasma exchange, cytotoxic therapy, and IV immunoglobulins.33 NEUROLOGIC EMERGENCIES Neurologic disease can result from accelerated atherosclerosis, direct involvement by the primary disease, vasculitis, arterial aneurysm, rupture or dissection, embolism, or infection. 36 Libman-Sacks valvular endocarditis of lupus can result in embolism of valve vegetations. Vasculitis of the cerebral vessels, with vessel rupture or occlusion, may lead to ischemic or hemorrhagic stroke. IV tissue plasminogen activator and thrombectomy have been successfully used to treat ischemic stroke in patients with lupus. 36-40 However, patients with CNS vasculitis should be considered at higher risk for post–tissue plasminogen activator hemorrhage.
upture or occlusion, may lead to ischemic or hemorrhagic stroke. IV tissue plasminogen activator and thrombectomy have been successfully used to treat ischemic stroke in patients with lupus. 36-40 However, patients with CNS vasculitis should be considered at higher risk for post–tissue plasminogen activator hemorrhage. 41,42 Although less common, giant cell arteritis can affect the extracranial vasculature, causing transient ischemic attacks, especially involving the vertebrobasilar circulation, with signs and symptoms of vertigo, hearing loss, gait disturbance, and other focal neurologic deficits involving the brainstem. Neurologic disease can also manifest as a consequence of therapy for systemic rheumatic diseases. 43 Tumor necrosis factor-α inhibitors increase the risk for herpes zoster outbreaks, especially multiderma tomal and zoster ophthalmicus. 43 Lupus and rheumatoid arthritis are independent risk factors for herpes zoster outbreaks.44 SPINAL CORD COMPRESSION AND SPINAL FRACTURES Degenerative disease of the cervical spine may result in acute spinal cord compression, gait abnormalities, paresthesias, or obstructive hydrocephalus in patients with rheumatoid arthritis and ankylosing spondylitis. Rigidity and osteoporosis of the spine in ankylosing spondylitis increase the risk for fracture and spinal cord injury. Occult fracture of the ankylosed spine may occur, even in the absence of trauma, and may result in acute radiculopathy, paralysis, or death from complications. 45 The most common symptom is severe and progressive pain. CT and/or MRI are recommended for evaluation. INSTABILITY OF THE CERVICAL SPINE The atlantoaxial joint is a preferred target of rheumatoid arthritis and less commonly, ankylosing spondylitis. Instability of the cervical spine and spontaneous atlantoaxial subluxation can result in acute cervical myelopathy, even after minor trauma. The signs and symptoms that raise suspicion for an unstable cervical spine are severe neck pain with occipital radiation and paresthesias involving the upper extremities. Instability may produce vertigo or other signs of vertebral insufficiency. Atlantoaxial instability can be clinically silent, so avoid neck flexion and extension (especially during intubation) in the patient with rheumatoid arthritis as well as ankylosing spondylitis. After even mild trauma or if neurologic symptoms as described earlier develop, keep the cervical spine stabilized. CT of the cervical spine will detect fracture, but MRI is needed to assess spinal cord integrity. Neurosurgical (or orthopedic spine specialist) consultation is needed for management. TRANSVERSE MYELITIS Transverse myelitis is a rare, devastating acute inflammatory process affecting a focal area of the spinal cord that may lead to rapid onset of irreversible paraplegia. It is clinically manifested with acute or subacute progressive symptoms and signs of neurologic dysfunction of the spinal cord. The clinical picture may be insidious at the beginning, with weakness, back or limb pain, urinary retention, and autonomic and sensory deficits. 46 Transverse myelitis occurs more commonly in patients with Sjögren’s syndrome,47 eosinophilic granulomatosis with polyangiitis, and also systemic lupus erythematosus, in whom acute transverse myelitis may be the initial manifestation. 48 Management includes high-dose corticosteroids and immunosuppressive agents at the direction of the rheumatology and/or neurology consultants. The clinical picture of transverse myelitis may also be caused by vas culitis, arterial thrombosis, embolism, or artery dissection.
myelitis may be the initial manifestation. 48 Management includes high-dose corticosteroids and immunosuppressive agents at the direction of the rheumatology and/or neurology consultants. The clinical picture of transverse myelitis may also be caused by vas culitis, arterial thrombosis, embolism, or artery dissection. An anterior spinal artery syndrome may be observed in other rheumatic diseases and is caused by blood supply impairment secondary to dissection of the aorta, vasculitis, or embolism involving the anterior spinal artery. The clinical picture is indistinguishable from transverse myelitis. OCULAR EMERGENCIES The eye is a sensitive barometer for onset or flare of rheumatic diseases.49 Ocular pain or discomfort, vision disturbances, red eye, tearing, photo phobia, diplopia, or reduced visual acuity should lead to careful evaluation (Table 282-4). Optic neuritis and keratitis are complications of systemic rheumatic diseases and are discussed in Chapter 241, “Eye Emergencies. ” Sudden and permanent blindness is also a concern in temporal or giant cell arteritis, a systemic disease that may lead to vasculitis and ischemia and that affects middle-aged to elderly individuals. The patient may report amaurosis fugax and complain of new headache, tender scalp, visual disturbance, or jaw claudication. Frequently, vision loss is the presenting feature of giant cell arteritis. To prevent permanent vision loss, high-dose steroids are administered based on the clinical diagnosis, even before biopsy of the temporal artery (see Chapter 241). RENAL EMERGENCIES The kidney is frequently involved in systemic rheumatic disease and is a major factor leading to morbidity and mortality. A decline in renal function should prompt careful observation and follow-up in any rheumatic disease patient. Kidney impairment may be related to the rheumatic disease itself, the results of therapy, or both. Acute nephritic syndrome, renal thrombotic events, and renal artery lesions are other possible causes of acute renal failure. In polyarteritis nodosa, rupture of arterial aneurysms can cause a perirenal hematoma. Scleroderma renal crisis is a true rheumatic emergency because it is associated with high mortality and requires prompt involvement of rheumatology and nephrology. Scleroderma renal crisis typically devel ops early in the course of systemic sclerosis, with 75% of cases occurring Tintinalli_Sec23_p1881-1932.indd 1910 8/2/19 3:15 PM
renal crisis is a true rheumatic emergency because it is associated with high mortality and requires prompt involvement of rheumatology and nephrology. Scleroderma renal crisis typically devel ops early in the course of systemic sclerosis, with 75% of cases occurring Tintinalli_Sec23_p1881-1932.indd 1910 8/2/19 3:15 PM CHAPTER 282: Systemic Rheumatic Diseases 1911 during the first 4 years after the onset of disease. 50 The prior use of glu cocorticoids has also been implicated in precipitating scleroderma renal crisis. It is more common with patients with diffuse systemic sclerosis and presents with abrupt and rapid deterioration in renal function along with hypertensive encephalopathy. Microangiopathic anemia frequently accompanies the other features. The mainstay of therapy in scleroderma renal crisis is effective and prompt blood pressure control with angiotensin-converting enzyme inhibitors. 51 Start captopril, 6.25 to 12.5 milligrams PO three times daily, and increase as tolerated.51 Enalaprilat can be used if PO therapy is not possible. Second-line choice is a calcium channel blocker. 51 Dialysis is required in 50% of patients initially, but more than half will recover renal function. Distal renal tubular acidosis occurs in patients with primary Sjögren’s syndrome. This condition is characterized by hyperchloremic metabolic acidosis with low bicarbonate levels and hypokalemia. Consider hypo kalemia as a cause of progressive weakness in patients with Sjögren’s syndrome. Hypokalemia is corrected with standard treatment (see Chapter 17, “Fluids and Electrolytes”). GI EMERGENCIES GI emergencies are outlined in Table 282-5. GI complications include ischemia (primarily due to vasculitis), infarction, perforation, vascular rupture, infection (e.g., cholecystitis, diverticulitis), and hemorrhage. TABLE 282-4 Ocular Emergencies in Patients With Systemic Rheumatic Diseases
ctrolytes”). GI EMERGENCIES GI emergencies are outlined in Table 282-5. GI complications include ischemia (primarily due to vasculitis), infarction, perforation, vascular rupture, infection (e.g., cholecystitis, diverticulitis), and hemorrhage. TABLE 282-4 Ocular Emergencies in Patients With Systemic Rheumatic Diseases Ankylosing Spondylitis Behçet’s Disease Churg-Strauss Syndrome Giant Cell (Temporal) Arteritis Polyarteritis Nodosa Rheumatoid Arthritis Relapsing Polychondritis Systemic Lupus Erythematosus Sjögren’s Syndrome Granulomatosis With Polyangiitis Ocular Episcleritis x x x Ischemic eye complications x x x x Scleritis x x x x x Optic neuritis x x x Peripheral ulcerative keratitis x x x x x x Retinal vasculitis x x Scleromalacia perforans x Uveitis x x x x x TABLE 282-5 GI and Other Emergencies in Patients With Systemic Rheumatic Diseases Adult Still’s Disease Antiphospholipid Syndrome Behçet’s Disease Churg-Strauss Syndrome Henoch-Schönlein Purpura Microscopic Polyangiitis Polyarteritis Nodosa Rheumatoid Arthritis Systemic Lupus Erythematosus Sjögren’s Syndrome Systemic Sclerosis Takayasu’s Arteritis Granulomatosis With Polyangiitis GI Acute pancreatitis x x x x x Bowel perforation x x x x x x x Esophageal necrosis with perforation x GI bleeding x x x x x x x Mesenteric vasculitis and ischemia x x x x x x x x Severe hepatic failure x Other emergencies Acute scrotum x x Adrenal insufficiency x Disseminated intravascular coagulation x x Hemolytic anemia x x Microangiopathic hemolytic anemia x x x x Pure red cell aplasia x x Thrombotic thrombocytopenic purpura x x Tintinalli_Sec23_p1881-1932.indd 1911 8/2/19 3:15 PM
m x x Adrenal insufficiency x Disseminated intravascular coagulation x x Hemolytic anemia x x Microangiopathic hemolytic anemia x x x x Pure red cell aplasia x x Thrombotic thrombocytopenic purpura x x Tintinalli_Sec23_p1881-1932.indd 1911 8/2/19 3:15 PM 1912 SECTION 23: Musculoskeletal Disorders Vasculitis is the most common GI manifestation and may affect any size vessel. Bowel ischemia can be the result of the same pathophysiologic process that leads to acute coronary syndrome, embolic phenomenon, or mesenteric artery vasculitis. The patient may complain of symptoms consistent with “intestinal angina” prior to bowel infarction. Due to chronic or recurrent ischemia, the bowel may develop wall edema, strictures, and stenosis. These changes may account for colicky abdominal pain, diverticular disease, intestinal obstruction, or episodes of paralytic ileus. Lupus mesenteric vasculitis is one of the most serious complications of systemic lupus erythematosus, with mortality of 13%. 52 Leukopenia, hypoalbuminemia, and elevated serum amylase are associated with poor outcome. Acute pancreatitis can be a result of several systemic rheumatic diseases or a result of many of the therapies (notably azathioprine). INFECTIOUS EMERGENCIES Rheumatic diseases predispose to infection in several ways, including immunocompromise at baseline and medications that induce immunosuppression (see “ Adverse Drug Reactions” section later in this chapter for infections associated with specific immunosuppressant drugs used to manage systemic rheumatic diseases). Differentiating flares of sys temic rheumatic diseases, such as rheumatoid arthritis or systemic lupus erythematosus, is difficult. 53 Using an elevated procalcitonin level of 0.5 nanogram/mL is 90% specific for sepsis in patients with autoimmune diseases but is only 68% to 75% sensitive for acute infection. 54,55 For acutely ill patients, empiric antibiotics are indicated until infection can be excluded. In general, isolated organisms do not differ from the normal population, although certain rheumatic diseases may leave patients more susceptible to atypical infections. For example, patients with systemic lupus erythematosus are more likely to have infections from encapsu lated bacteria (e.g., Salmonella), although typical infections are still more common. Regardless, the differential for infectious causes should always remain broad because both the underling disease itself as well as chronic immunosuppressive therapy may predispose patients with systemic rheumatic disease to opportunistic infections (e.g., Candida, Pneumocystis jirovecii, Legionella, Mycobacterium tuberculosis). While symptoms of septic arthritis may mimic flares of the underlying rheumatic disease, care must be taken to rule out infection with aspiration of the involved joint if indicated. The risk of septic arthritis is increased in any joint with preexisting arthritis. Thus, patients with joint-destructive disease such as rheumatoid arthritis are at high risk of developing septic arthritis, which is often amplified by the immunosuppressive medications used to treat their disease. The prevalence of septic arthritis is doubled in patients with rheumatoid arthritis who are treated with glucocorticoids or tumor necrosis factor-α blockers. 56,57 The physical findings of severe pain and limited range of motion may be absent in cases of septic arthritis in patients with systemic rheumatic disease. 58 Patients suspected of having septic arthritis should have arthrocentesis prior to initiation of antibiotic therapy. It is important to remember that the presence of a crystalline arthropathy (e.g., gout) does not exclude the possibility of concurrent septic arthritis.
tis in patients with systemic rheumatic disease. 58 Patients suspected of having septic arthritis should have arthrocentesis prior to initiation of antibiotic therapy. It is important to remember that the presence of a crystalline arthropathy (e.g., gout) does not exclude the possibility of concurrent septic arthritis. If the clinical suspicion for septic arthritis is high, it is prudent to start antibiotics after aspiration, consult orthopedics, and admit the patient while awaiting cultures. See Chapter 284, “Joints and Bursae, ” for further discussion of diagnosis and treatment. OTHER EMERGENCIES Several hematologic complications and other emergencies are encoun tered in patients with rheumatic diseases (Table 282-5). Anemia, thrombocytopenia, leukopenia, and coagulation abnor malities are some of the important hematologic emergencies. Severe hemolytic anemia may develop in systemic lupus erythematosus (autoimmune) and in systemic sclerosis during renal crisis (micro angiopathic). Thrombocytopenia may be present in systemic lupus erythematosus and also observed in antiphospholipid syndrome patients; it may present as thrombotic thrombocytopenic purpura. A low WBC count may occur as a part of underlying disease or secondary to immu nosuppressive regimens. Pancytopenia may be observed when the rheumatic disease itself affects all the cellular lines in acute hemophagocytic syndrome and in medullar suppression secondary to cytotoxic drugs. In autoimmune hematologic emergencies, transfusion of blood product may carry some risk of transfusion reaction. Patients with steroid-dependent rheumatic diseases are at risk for acute adrenal insufficiency either from unexpected stressors (illness, surgery) or from abrupt cessation of prescribed steroid medication. Orchitis is one of the most characteristic manifestations of polyarteritis nodosa, and scrotal involvement may be found in boys with Henoch- Schönlein purpura. Clinical findings include pain, tenderness, and swelling of the involved testicle and/or scrotum. The presentation may mimic testicular torsion. Ultrasonography confirms the correct diagnosis. RAYNAUD’S PHENOMENON Raynaud’s phenomenon, digital ulcers, and rash are some examples of skin manifestations. While often benign in nature, Raynaud’s phenomenon can rarely have disastrous consequences including gangrene and loss of digits. 59 These serious complications are rarely seen in primary Raynaud’s phenomenon and are most frequently seen in patients with systemic sclerosis. Failure of the Raynaud’s phenomenon to resolve, either manifested as consistently blue fingers or ulcerations, is an emergency. 59 Warming techniques (both core and peripheral) should be initiated immediately, but with insufficient response, oral calcium channel blockers and topical nitroglycerin paste applied to the webbed spaces can help to save tissue. 59,60 Depending on the severity, admission to the hospital may be indicated for more aggressive intervention (e.g., IV prostacyclin, surgical sympathectomy) and pain control. ADVERSE DRUG REACTIONS Table 282-6 lists the more common clinical manifestations of adverse reactions associated with drugs used to manage systemic rheumatic diseases. When patients with systemic rheumatic diseases develop new alarming and unexplained symptoms, a drug reference guide or similar resource should be consulted for a listing of rare adverse drug reactions. IMMUNOSUPPRESSION IMMUNOSUPPRESSION CAUSED BY DRUGS USED TO MANAGE SYSTEMIC RHEUMATIC DISEASES Immunosuppressants and disease-modifying antirheumatic drugs are used to treat multiple types of systemic rheumatologic diseases with the aim to induce or maintain remission, to reduce exacerbations or relapse, and/or to allow tapering of glucocorticoids.
SSION CAUSED BY DRUGS USED TO MANAGE SYSTEMIC RHEUMATIC DISEASES Immunosuppressants and disease-modifying antirheumatic drugs are used to treat multiple types of systemic rheumatologic diseases with the aim to induce or maintain remission, to reduce exacerbations or relapse, and/or to allow tapering of glucocorticoids. These drugs have a variety of actions that are not completely understood but that modify critical pathways in the inflammatory process. They may cause immunosuppression primarily or as a side effect and lead to secondary diseases, infections, and reactivation of latent diseases or malignancies (Table 282-7). 61-68 Risk factors for infection during immunosuppression include the drug, dose, duration of use, concomitant use of immunomodulators, the nature of the disease process, the functional status of the patient, healthcare facility exposure, and older age. 69 For the treatment of systemic rheumatic disease, immunosuppressive therapies are often used in combination especially with glucocorticoids, enhancing the risk of infection. In particular, glucocorticoid therapies are associated with a dosedependent increase in risk of infection.70 The immunosuppressive properties of glucocorticoids are thought to be from the impact on both the innate and acquired immune system, which occurs through a variety of inhibitory mechanisms. Immediate effects on the innate immune system include decreased phagocyte migration, eosinophil apoptosis, decreased macrophage production and function, decreased degranulation of mast cells, decreased inflammatory cytokine production, and decreased pro inflammatory mediators. Neutrophils are affected by decreased ability to bind to and exit the endothelium, increased release from bone marrow, and decreased apoptosis resulting in increased overall leukocytosis but decreased effectiveness. Acquired immunity is also affected by a decrease in dendritic cells, rapid depletion of T cells, increased apoptosis of CD4 and CD8 cells, Tintinalli_Sec23_p1881-1932.indd 1912 8/2/19 3:15 PM CHAPTER 282: Systemic Rheumatic Diseases 1913 TABLE 282-6 Common Clinical Manifestations of Adverse Reactions to Drugs Used to Manage Systemic Rheumatic Diseases
These drugs have a variety of actions that are not completely understood but that modify critical pathways in the inflammatory process. They may cause immunosuppression primarily or as a side effect and lead to secondary diseases, infections, and reactivation of latent diseases or malignancies (Table 282-7). 61-68 Risk factors for infection during immunosuppression include the drug, dose, duration of use, concomitant use of immunomodulators, the nature of the disease process, the functional status of the patient, healthcare facility exposure, and older age. 69 For the treatment of systemic rheumatic disease, immunosuppressive therapies are often used in combination especially with glucocorticoids, enhancing the risk of infection. In particular, glucocorticoid therapies are associated with a dosedependent increase in risk of infection.70 The immunosuppressive properties of glucocorticoids are thought to be from the impact on both the innate and acquired immune system, which occurs through a variety of inhibitory mechanisms. Immediate effects on the innate immune system include decreased phagocyte migration, eosinophil apoptosis, decreased macrophage production and function, decreased degranulation of mast cells, decreased inflammatory cytokine production, and decreased pro inflammatory mediators. Neutrophils are affected by decreased ability to bind to and exit the endothelium, increased release from bone marrow, and decreased apoptosis resulting in increased overall leukocytosis but decreased effectiveness. Acquired immunity is also affected by a decrease in dendritic cells, rapid depletion of T cells, increased apoptosis of CD4 and CD8 cells, Tintinalli_Sec23_p1881-1932.indd 1912 8/2/19 3:15 PM CHAPTER 282: Systemic Rheumatic Diseases 1913 TABLE 282-6 Common Clinical Manifestations of Adverse Reactions to Drugs Used to Manage Systemic Rheumatic Diseases Abdominal Pain Acute/Hemorrhagic Cystitis Adrenal Insufficiency Alopecia Anaphylaxis Anemia COPD Exacerbation Dermatologic Manifestations Diarrhea Diverticulitis Fatigue/Malaise GI Bleed Hepatic Enzyme Elevation Immunosuppression/Infection Injection Site Reaction Leukopenia Nausea and Vomiting Ophthalmic Impairment Psychiatric Symptoms Pulmonary Fibrosis Renal Impairment Stomatitis/Oral Ulcers Thrombocytopenia Abatacept X X X X X X X TNF-α inhibitors * X X X X Apremilast X X X X X X X Azathioprine X X X X X X X Belimumab X X X X X X X X Cyclophosphamide X X X X X X Glucocorticoid X X X X Hydroxychloroquine X X X Interluekin-1 inhibitors (anakinra, canakinumab) X X X X Leflunomide X X X X X X X X X Methotrexate X X X X X X X X X X X Mycophenolate X X X X X X X X X X NSAID X X X X Rituximab X X X X X X X X Sulfasalazine X X X X X X X X Secukinumab X X X X X Tocilizumab X X X X X X X X X X X Tofacitinib X X X X X X X X Ustekinumab X X X Abbreviations: COPD = chronic obstructive pulmonary disease; TNF = tumor necrosis factor. *Adalimumab, etanercept golimumab, infliximab, certolizumab pegol. TABLE 282-7 Drugs Used to Treat Rheumatic Diseases and Common Infections Associated With Their Respective Use Drug Common Infections Associated With Agent Abatacept Pneumonia, URI, pharyngitis, UTI. TNF-α inhibitors* URI, sinusitis, pharyngitis. Reactivation of TB. Apremilast URI, bronchitis, pharyngitis, influenza. Azathioprine Reactivation of latent viruses, bacteremia, interstitial pneumonia. Lower rates of infection in RA patients compared to transplant. Belimumab Viral gastroenteritis, UTI, influenza, bronchitis, URI, sinusitis. Cyclophosphamide Reactivation of latent viruses, sepsis ( Salmonella, Staphylococcus, Meningococcus), URI, pneumonia, opportunistic infections. Glucocorticoid High rate of infection with both typical and atypical pathogens. Hydroxychloroquine Overall infection is low. Interluekin-1 inhibitors (anakinra, canakinumab) Nasopharyngitis, cellulitis, URI. Leflunomide URI, bronchitis, pharyngitis, skin abscess. Methotrexate Viral infections, CMV, EBV, reactivation of latent viruses. Mycophenolate Viral infections, CMV, HSV, VZV. Candidiasis, URI. NSAID None Rituximab Pneumonia, cerebral toxoplasmosis. Reactivation of latent viruses. Progressive multifocal leukoencephalopathy due to JC virus reactivation. Sulfasalazine Overall serious infection risk is low but increased in the setting of neutropenia. Secukinumab Nasopharyngitis. URI. Herpes virus infection, staphylococcal infection. Tocilizumab Pharyngitis, rhinitis, conjunctivitis, diverticulitis. Tofacitinib URI, nasopharyngitis, diverticulitis. Ustekinumab Nasopharyngitis, URI, sinusitis. Vaginal mycosis and candidiasis. Abbreviations: CMV = cytomegalovirus; EBV = Epstein-Barr virus; HSV = herpes simplex virus; JC = John Cunningham; RA = rheumatoid arthritis; TB = tuberculosis; TNF = tumor necrosis factor; URI = upper respiratory infection; UTI = urinary tract infection; VZV = varicella-zoster virus.
s. Vaginal mycosis and candidiasis. Abbreviations: CMV = cytomegalovirus; EBV = Epstein-Barr virus; HSV = herpes simplex virus; JC = John Cunningham; RA = rheumatoid arthritis; TB = tuberculosis; TNF = tumor necrosis factor; URI = upper respiratory infection; UTI = urinary tract infection; VZV = varicella-zoster virus. *Adalimumab, etanercept golimumab, infliximab, certolizumab pegol. Tintinalli_Sec23_p1881-1932.indd 1913 8/2/19 3:15 PM