Musculoskeletal and Autoimmune Disorders

Musculoskeletal and Autoimmune Disorders

10.1 Systemic Lupus Erythematosus

Debra D. Pulley

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that can cause multiorgan damage. The etiology of SLE is not clear but there appears to be a genetic susceptibility with environmental or infectious agents that precipitate altered immune function (1,2). The tissue damage results from deposition of immune complexes with activation of complement and other mediators of inflammation (2). Vasculopathy and thrombophilia contribute to organ dysfunction (1). The incidence of SLE in the United States is about 73 per 100,000, is more common in women and African Americans with a peak age of onset between 15 and 40 years (1,2).

The diagnosis of SLE is based on the patient’s history (including family history), clinical manifestations, and pertinent immunologic laboratory studies or biopsy. The American College of Rheumatology (ACR) developed a list of criteria to classify patients for research purposes (1,3). Due to imperfect sensitivity/specificity and to improve clinical relevance, the Systemic Lupus International Collaborating Clinics (SLICC) developed a different list of criteria. A patient is classified as having SLE when 4 of 17 criteria are met (with at least one clinical and one immunologic) or has biopsy-proven lupus nephritis (3). Criteria include:

  • Clinical

    • Acute cutaneous lupus (e.g., malar rash)

    • Chronic cutaneous lupus (e.g., classic discoid rash)

    • Nonscarring alopecia

    • Oral or nasal ulcers

    • Joint disease—either synovitis or tenderness in ≥2 joints

    • Serositis—either pleural (pleurisy, effusion, or rub) or pericardial (pain, effusion, rub)

    • Renal—either proteinuria or red blood cell casts

    • Neurologic—seizures, psychosis, neuritis, myelitis, peripheral/cranial neuropathy, acute confusional state

    • Hemolytic anemia

    • Leukopenia or lymphopenia

    • Thrombocytopenia

  • Immunologic

    • Elevated antinuclear antibody (ANA) level

    • Elevated anti-double-stranded DNA level

    • Presence of anti-smooth muscle antibody

    • Antiphospholipid antibody positive (positive lupus anticoagulant, medium/high titer anticardiolipin, positive anti-beta-2 glycoprotein 1)

    • Low complement

    • Positive direct Coombs test in the absence of hemolytic anemia

Even with the newer classification criteria, a patient with suspected SLE will be managed similarly to one who can be classified as definite SLE once other diagnoses are eliminated.

A different type of lupus disease is drug-induced lupus. Patients tend to have milder symptoms (arthralgias/serositis) than SLE which disappear after cessation of the offending medication (e.g., hydralazine, procainamide) (2).


The clinical manifestations of SLE are varied and any organ can be affected. Severity varies from mild to severe and typically there are periods of disease flares interspersed with stability (1). Potential manifestations are (1,2,3):

  • General—fatigue, malaise, weight loss, fevers

  • Dermatologic—rashes, photosensitivity, mucositis, oral, nasal or genital ulcers, nonscarring alopecia

  • Musculoskeletal—arthralgias, myalgias, arthritis, myositis, osteoporosis, atlantoaxial subluxation

  • Renal—nephritis, proteinuria, hematuria, nephrotic syndrome, end-stage renal disease (ESRD)

  • Hematologic/immunologic—autoantibodies, hemolytic anemia, thrombocytopenia, leukopenia, lymphopenia, lymphadenopathy, splenomegaly, hematologic malignancies

  • Respiratory—pleurisy, pleural effusion, pneumonitis, interstitial lung disease, pulmonary hypertension, pulmonary alveolar hemorrhage, vocal cord paralysis, subglottic stenosis, laryngeal edema, epiglottitis, rheumatoid nodules, inflammatory masses, cricoarytenoiditis

  • Cardiovascular—vasculitis, Raynaud’s, thromboembolic disease, premature atherosclerosis, carotid vascular disease, pericarditis, pericardial effusion, pericardial tamponade, valvular disease, myocarditis, arrhythmias, coronary artery disease, myocardial infarction, cardiomyopathy, Libman-Sacks endocarditis

  • Neuropsychiatric—headaches, cognitive dysfunction, psychosis, acute confusional state, neuritis, peripheral/cranial neuropathy, myopathy, movement disorder, transverse myelitis, seizures, cerebrovascular disease, white matter lesions, cerebral infarction, venous sinus thrombosis, atrophy

  • Gastrointestinal—abdominal pain, elevated liver enzymes, pancreatitis, esophagitis, bowel necrosis from mesenteric vasculitis/ischemia

  • Pregnancy—increased risk of miscarriage and poor fetal outcome


Treatment of SLE involves immunosuppressive and anti-inflammatory medications. Topical or low-dose oral corticosteroids, NSAIDs, and antimalarial medications are used for mild cases (1). High-dose corticosteroids, alkylating
agents (cyclophosphamide), purine synthesis inhibitors (azathioprine, mycophenolate mofetil), methotrexate, intravenous gamma globulin, plasmapheresis, and biologic therapies (belimumab, rituximab, monoclonal antibodies) are used when there is significant organ involvement (1). Aggressive medical treatment is recommended for patients with hypertension or thrombophilia (1). Mortality in patients with SLE is bimodal with early death caused by either active lupus or severe infections from immunosuppressants. Late death is caused by cardiovascular disease from the atherosclerotic effects of SLE and chronic steroid use (4). Males and patients with later-onset-age disease tend to have a worse prognosis (2).


Since both active lupus and chronic steroids affect the musculoskeletal system (avascular necrosis, osteoarthritis, osteoporosis, and vertebral fractures), many patients undergo orthopedic procedures (5). There is an increased risk of perioperative complications and mortality in patients with SLE undergoing hip arthroplasty, but not knee arthroplasty (5). Complications include increased transfusions, hematomas, thrombosis, infections, aseptic loosening, prosthesis dislocation, longer hospital stay, falls, deep vein thrombosis, AKI, superficial wound infections, and requiring revisions (5). SLE patients may present for kidney transplantation or cardiovascular procedures.

Depending on the extent of the tissue damage and complications of treatment, patients with SLE have high rates of perioperative morbidity and mortality. The stress of surgery can cause disease flares. Data from a national database in Taiwan (4) showed that the odds ratio (OR) of 30-day mortality for patients with SLE having major surgery was 1.71 compared to patients without SLE. Hospitalization in the 6 months before a major surgery increased the OR of developing AKI, pulmonary embolism, stroke, sepsis, and 30-day mortality. The authors proposed that prior hospitalization, especially for the purpose of giving a steroid burst, is a marker for the severity of the patient’s disease (4).

Preoperative assessment includes evaluating the extent of tissue involvement and the degree of organ damage especially in regards to the airway (laryngeal involvement, cervical subluxation), pulmonary, cardiovascular, renal, hematologic, and neuropsychiatric systems. Preoperative tests such as CBC, BMP, and ECG should be obtained. Based on the history and physical examination and the surgery planned, other tests may be indicated such as chest radiography (CXR), liver panel, coagulation studies, cardiac workup (echocardiogram, stress test), and cervical neck evaluation (neck flexion/extension or MRI). Identification of patients with APS is important due to an overall higher risk of arterial and VTE (6). Consultation with the patient’s rheumatologist to discuss the status of disease and management of immunosuppressive and anticoagulant medications should be considered. A careful assessment of medications is necessary with a determination whether to discontinue immunosuppressive agents (see Table 10.1) or anticoagulants (with bridging therapy if indicated based on the risk of thrombosis) (7). Patients may need additional steroids perioperatively to prevent acute adrenal insufficiency. Elective surgery is delayed during a flare or if there is an acute infectious process.

TABLE 10.1 Usual Recommended Perioperative Medication Management

Immunosuppressive/Anti-inflammatory agent

Perioperative management (Need to individualize by considering the patient’s disease severity and the surgery planned)

Abatacept (Biologic DMARD)

Discuss with prescriber—usually wait one to two treatment cycles

Azathioprine (DMARD—purine synthesis inhibitor)

Discuss with prescriber—usually stop 1 week before surgery

Belimumab (Biologic DMARD)

Discuss with prescriber—usually wait one to two treatment cycles

Chloroquine (DMARD—antimalarial)



Continue, but patient should be on the minimal steroid dose for disease control

Cyclophosphamide (DMARD—alkylating agent)

Discuss with prescriber

Cyclosporine (DMARD)

Discuss with prescriber

Hydroxychloroquine (DMARD—antimalarial)


Intravenous immune globulin

Discuss with prescriber—used in severe flares, best to delay elective surgery until SLE is stable

Methotrexate (DMARD)

Continue, if renal function not normal discuss with prescriber—usually hold for 1-2 weeks

Mycophenolate mofetil (DMARD—purine synthesis inhibitor)

Discuss with prescriber


Stop 1-7 days depending on half-life, continue aspirin if for CAD and surgery permits

Rituximab (Biologic DMARD)

Discuss with prescriber—usually wait one to two treatment cycles

SLE, systemic lupus erythrmatosis; DMARD, disease modifying antirheumatic drug; NSAID, nonsteroidal anti-inflammatory drug; CAD, coronary artery disease


1. Crow MK. Systemic lupus erythematosus. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine. 25th ed. Philadelphia, PA: Saunders; 2016:1769-1777.

2. Ben-Meanchem EB. Systemic lupus erythematosus: a review for anesthesiologists. Anesth Analg. 2010;111:665-676.

3. Petri M, Orbai AM, Alarcón GS, et al. Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64:2677-2686.

4. Lin JA, Liao CC, Lee YJ, et al. Adverse outcomes after major surgery in patients with systemic lupus erythematosus: a nationwide population-based study. Ann Rheum Dis. 2014;73:1646-1651.

5. Kasturi S, Goodman S. Current perspectives on arthroplasty in systemic lupus erythematosus: rates, outcomes, and adverse events. Curr Rheumatol Rep. 2016;18:59.

6. Pons-Estel GJ, Andreoli L, Scanzi F, et al. The antiphospholipid syndrome in patients with systemic lupus erythematosus. J Autoimmun. 2017;76:10-20.

7. Bissar L, Almoallim H, Albazli K, et al. Perioperative management of patients with rheumatic diseases. Open Rheumatol J. 2013;7:42-50.

10.2 Sarcoidosis

Debra D. Pulley

Sarcoidosis is a systemic inflammatory disease that causes granulomas to form in various tissues (1). The trigger is unknown, but the disease is thought to occur as a result of interactions between immunologic, environmental, and genetic factors (2,3). The granulomas are typically discrete, well formed, compact, noncaseating, composed of epithelioid cells, giant cells, macrophages, and plasma cells surrounded by lymphocytes (4,5). There may also be a focal central coagulative necrosis (4). Eventually, the granulomas either resolve or fibrose (4). The incidence of sarcoidosis in the United States is about 10 to 35 per 100,000 (1). It can affect all ethnic and racial groups, but there is increased incidence in people with Scandinavian, Irish, German, and West Indian descent, in addition to, African Americans (two to three times) (1). It usually occurs between the ages of 25-29 years, but there is a second peak in women over the age of 50 in other parts of the world (4). Sarcoidosis may resolve spontaneously, but many patients have chronic or progressive disease leading to significant morbidity and mortality from the disease and the treatments (6). The original staging of sarcoidosis is based on CXR and ranges from Stages 0 to IV with the higher the stage the worse the prognosis (2). The worst prognosis is with respiratory complications and with cardiac or central nervous system involvement (2). Significant morbidity can occur with hepatic and ocular involvement (6).


Sarcoidosis can affect any organ. Signs and symptoms are nonspecific including the presence of tissue granulomas (1). The lungs, eyes, skin, and lymphatic system are most frequently affected (2). The disease can be acute, subacute, chronic, or progressive (6). Up to 50% of patients present with asymptomatic bilateral hilar adenopathy found on CXR (1). Other classic presentations include Löfgren syndrome (bihilar lymphadenopathy, bilateral arthritis of the ankles, erythema nodosum, and general flu-like symptoms) and Heerfordt syndrome (uveitis, parotitis, Bell palsy, and fever) (2). Ultimately, 90% of patients will have pulmonary manifestations and an abnormal CXR (2). High-resolution computed tomography (CT) is more sensitive for detection of adenopathy and subtle parenchymal disease (5). Pulmonary fibrosis and pulmonary hypertension are independent risk factors for mortality (6). The frequency
of airway involvement increases as pulmonary parenchymal disease progresses and is associated with increased morbidity and mortality (7). Airway effects include mucosal erythema, edema, hoarseness, dysphagia, laryngeal paralysis, airway obstruction, obstructive sleep apnea (OSA), airway hyperreactivity, bronchiectasis, bronchiolitis, and external compression (7). Symptoms of sarcoidosis include persistent cough, fever, arthralgias, visual changes, skin lesions, dyspnea on exertion, or simply fatigue (1,2). Cardiac symptoms occur in 5% of patients, although actual involvement of the heart is close to 25% (2). Cardiac manifestations include high-degree atrioventricular (AV) block, ventricular tachycardias, and cardiomyopathy (2). Nervous system manifestations include cranial neuropathy (especially, cranial nerve VII), involvement of the hypothalamus and pituitary gland (leading to hypoglycemia, impaired temperature regulation, DI, SIADH), papillary edema, increased intracranial pressure, hydrocephalus, aseptic meningitis, intracerebral lesions, seizures, spinal lesions, or psychiatric symptoms (2,8). Peripheral neuropathy can cause autonomic dysfunction, hypoesthesia, paresthesia, neuropathic pain, restless leg syndrome, and sleep disturbances (2). Hepatic involvement occurs in 70% of patients with sarcoidosis, but most are asymptomatic with elevated liver enzymes (3). Symptoms include abdominal pain, fatigue, pruritus, and jaundice. Chronic hepatic involvement can potentially lead to portal hypertension and cirrhosis (3). Esophageal involvement is not common. Symptoms can include dysphagia from muscle infiltration, enteric nervous plexus neuropathy, and external compression (9). The kidney can be affected by hypercalcemia and hypercalciuria that can occur with sarcoidosis or by granulomatous interstitial nephritis. Rarely, renal failure occurs (10).


Patients with sarcoidosis may present for diagnosis (biopsy of skin or lymph nodes, bronchoscopy, endobronchial ultrasonography-guided transbronchial biopsy), treatment of airway obstruction, or treatment of organ damage (procedures for treating arrhythmias, organ transplantation) (2,6). Significant involvement of the airway (obstruction) or vital organs (pulmonary fibrosis, pulmonary hypertension, arrhythmias, cardiomyopathy,
cirrhosis, and chronic kidney disease) increase perioperative morbidity and mortality. Survival of patients with sarcoidosis after transplantation is similar to patients who do not have sarcoidosis (6).

It is important to assess the affected organs and the extent of damage especially in regards to the airway, lungs, heart, liver, kidneys, central, and peripheral nervous systems. Patients should be screened for OSA. Depending on the history and physical exam, further testing such as ECG, echocardiogram, CBC, and serum creatinine may need to be performed preoperatively. Vital capacity, as measured on pulmonary function tests, is an important parameter for monitoring the course of the disease (2). Elective surgery is delayed until assessment is complete and the disease is optimally managed. If a patient has been treated with steroids, a steroid bolus perioperatively may be needed to prevent acute adrenal insufficiency.


1. Govender P, Berman JS. The diagnosis of sarcoidosis. Clin Chest Med. 2015;36:585-602.

2. Wessendorf TE, Bonnella F, Costabel U. Diagnosis of sarcoidosis. Clin Rev Allergy Immunol. 2015:49:54-62.

3. Tadros M, Frouhar F, Wu GY. Hepatic sarcoidosis. J Clin Transl Hepatol. 2013;1:87-93.

4. Valeyre D, Bernaudin JF, Uzunham Y, et al. Clinical presentation of sarcoidosis and diagnostic work-up. Semin Respir Crit Care Med. 2014;35:336-351.

5. Criado E, Sánchez M, Ramírez J, et al. Pulmonary sarcoidosis: typical and atypical manifestations at high-resolution CT with pathologic correlation. Radiographics. 2010;30:1567-1586.

6. Gerke AK. Morbidity and mortality in sarcoidosis. Curr Opin Pulm Med. 2014;20:472-478.

7. Polychronopoulus VS, Prakash UB. Airway involvement in sarcoidosis. Chest. 2009; 136:1371-1380.

8. Arora V, Mallu S. Neurosarcoidosis: an illustrative case and review of perioperative considerations. Open J Anesthesiol. 2012;2:170-175.

9. Abraham A, Hajar R, Virdi R, et al. Esophageal sarcoidosis: a review of cases and an update. ISRN Gastroenterol. 2013;2013:9.

10. Hilderson I, Van Laecke S, Wauters A, et al. Treatment of renal sarcoidosis: is there a guideline? Overview of the different treatment options. Nephrol Dial Transplant. 2013;10:1841-1847.

10.3 Scleroderma and Systemic Sclerosis

Deborah C. Richman

Scleroderma (systemic sclerosis) is a rare autoimmune disease, with onset in middle age; and is three times more common in females. Scleroderma results from autoimmunemediated inflammatory vasculitis and subsequent fibrosis of skin and internal organs from abnormal deposition of extracellular collagen due to impaired fibroblast function (1). The etiology of scleroderma is unknown. The three main forms are:

  • Localized scleroderma (morphea) of which there are several types based on severity and distribution

    • Involvement of the skin of the face, trunk, and distal limbs

    • Sclerodactyly—sausage-shaped fingers (and toes) that are erythematous, swollen, and shiny due to tightening of the skin are common

    • Skin fibrosis can be complicated by necrosis

  • Limited cutaneous systemic sclerosis

    • Usually a combination of scleroderma features

    • CREST syndrome—calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia

    • Pulmonary involvement includes interstitial lung disease and pulmonary hypertension. Pulmonary hypertension is associated with poorer overall survival rates (2).

  • Diffuse cutaneous systemic sclerosis

    • Rapidly progressive disease, with generalized skin involvement and cardiovascular complications with vascular involvement, coronary artery disease, cardiomyopathy, and hypertension

Systemic sclerosis sine scleroderma is rare and has the classic internal organ presentation without the cutaneous manifestation (3).

Chronic renal involvement is found in >50% of systemic sclerosis patients. Acute renal failure (ARF) occurs in about 5% of patients. It is characterized by fulminant acute-onset kidney injury, severe hypertension, and normal urine sediment. Steroid therapy and pregnancy are associated with a higher incidence of ARF (4). There is an overlap with antiphospholipid syndrome, especially in pregnancy (5). There is also an overlap syndrome with polymyositis so a history of muscle pain should be elicited. Raynaud’s is found in >95% of patients with scleroderma. Airway involvement can make intubation difficult. Tightening of the skin around the mouth leads to a small oral opening. Skin fibrosis can limit neck extension. Oral telangiectasia can bleed on intubation. Sjögren syndrome is frequently associated with scleroderma and the chronic dry mouth leads to poor dentition. Difficult intravenous access is a hallmark of scleroderma. Contractures can affect positioning.


Careful airway assessment is mandatory. Severity of reflux symptoms are ascertained. Preoperative testing is shown in Table 10.3.

Antireflux medications, vasospasm, and pulmonary hypertension treatments are continued through the perioperative period. For management of immunosuppressives, see Table 10.2.

Hemoglobin should be optimized, especially before major surgeries. It is recommended to keep patient care areas at thermoneutral temperature of about 20°C to limit Raynaud symptoms. Pulse oximetry may be hampered by Raynaud’s, an ear

probe may give more reliable results. Arterial line placement carries higher than usual risk due to already poor circulation. VTE is three times more common in this population and appropriate prophylaxis is necessary (6).

TABLE 10.2 Immunosuppressive Therapies for Scleroderma/Recommendations for Holding Perioperatively


Skin only and possibly myositis


Hold if renal impairment or acute infection


Skin only



Skin and lung



Refractory scleroderma

Hold 2 weeks

Intravenous immunoglobulin

Refractory scleroderma




Hold 1 week


Overlap with polymyositis but best avoided due to increased risk of acute renal crisis


May need stress dose

TABLE 10.3 Preoperative Testing


Signs and symptoms of anemia

Severe pulmonary hypertension

Chronic blood loss from GI telangiectasia


Severe hypertension

Steroid use



Severe malnutrition


Prothrombin time


Severe malnutrition

Creatine phosphokinase

Muscle symptoms


Conduction abnormalities

Pulmonary hypertension


Ventricular function

Pulmonary hypertension

Arterial blood gas

Pulmonary hypertension

Interstitial lung disease

GI, gastrointestinal


1. Gilbane AJ, Denton CP, Holmes AM. Scleroderma pathogenesis: a pivotal role for fibroblasts as effector cells. Arthritis Res Ther. 2013;15(3):215.

2. Lefevre G, Dauchet L, Hachulla E, et al. Survival and prognostic factors in systemic sclerosis-associated pulmonary hypertension: a systematic review and meta-analysis. Arthritis Rheum. 2013;65(9):2412-2423.

3. Poormoghim H, Lucas M, Fertig N, et al. Systemic sclerosis sine scleroderma: demographic, clinical, and serologic features and survival in forty-eight patients. Arthritis Rheum. 2000;43(2):444-451.

4. Guillevin L, Berezne A, Seror R, et al. Scleroderma renal crisis: a retrospective multicentre study on 91 patients and 427 controls. Rheumatology. 2012;51(3):460-467.

5. Lidar M, Langevitz P. Pregnancy issues in scleroderma. Autoimmun Rev. 2012;11(6-7): A515-A519.

6. Schoenfeld SR, Choi HK, Sayre EC, et al. Risk of pulmonary embolism and deep venous thrombosis in systemic sclerosis: a general population-based study. Arthritis Care Res. 2016; 68(2):246-253.

10.4 Rheumatoid Arthritis

Deborah C. Richman

Rheumatoid arthritis (RA) is an autoimmune-mediated, systemic inflammatory disease. Females are affected three times more commonly than males in 1% of the population. All organ systems can be involved, but the primary presentation is pain and disability associated with destruction of synovial joints. RA is frequently associated with other autoimmune diseases and overlaps with other connective tissue diseases. Patients are often older and have many other associated morbidities. RA is characterized by morning stiffness that improves over the course of the day. Joint involvement starts with painful synovial inflammation, swelling, and increased synovial fluid. Disease progression leads to destruction of cartilage, periarticular osteopenia with pull-off of ligamentous insertions leading to deformities and instability. There is a very late stage with ankylosis of the joint.

Pertinent history includes age at onset, severity of disability and symptoms, affected organ systems, frequency and causes of disease flares, medications used to manage the disease, and comorbidities (Table 10.4). Clinical findings by organ system include:

Nov 14, 2018 | Posted by in ANESTHESIA | Comments Off on Musculoskeletal and Autoimmune Disorders

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