MSK Flashcards
What Is Systemic Sclerosis?
○ Systemic sclerosis is an autoimmune condition of connective tissue that is characterized by autoantibody production, fibrosis and matrix deposition in the skin, vasculature, and internal organs.
○ Small-vessel vasculopathy with endothelial cell injury results in diffuse capillary loss and leakage into the interstitial space.
○ It is a systemic multi-organ disease with skin, cardiac, pulmonary, renal, gastrointestinal, and musculoskeletal lesions.
○ Two clinical patterns of systemic sclerosis are recognized based on the extent of cutaneous involvement:
(a) limited cutaneous systemic sclerosis (lcSSc) with skin involvement usually limited to the hands (occasionally face and neck) and possible manifestations of CREST syndrome (calcinosis, Raynaud’s phenomenon, esophageal hypomotility, sclerodactyly, and telangiectasia), and
(b) diffuse cutaneous systemic sclerosis (dcSSc) with skin involvement
proximal to the wrists and the trunk.
What Is the Difference Between Scleroderma
and Systemic Sclerosis?
Sclerosis that is limited to the skin and subcutaneous tissue
of the hands and/or face is known as scleroderma.
What Specific Surgeries Is the Scleroderma Patient Likely to Present For?
• Debridement of digital gangrene
• Amputation of digits
• Periarterial, cervical, or lumbar sympathectomy to improve blood flow
• Repeated esophageal dilatation
• Laparotomy for intestinal pseudo-obstruction
• Lung transplantation due to pulmonary artery hypertension or ILD
What Systemic Complications Is the Patient with Systemic Sclerosis Subject To?
○ Systemic sclerosis is associated with a significant increase in mortality, most deaths are related to pulmonary fibrosis or pulmonary hypertension.
• Pulmonary disease is seen in over 70% of patients with systemic sclerosis and is the main cause of death in these patients. This is manifest as pulmonary hypertension or ILD. In the perioperative period, patients with pulmonary hypertension are at risk of acute right heart failure, congestive heart failure, arrhythmias, and respiratory failure. ILD develops due to interstitial and peri-bronchial fibrosis and bronchial epithelial proliferation. Patients with ILD are susceptible to an acute exacerbation of this condition, pneumonia, acute lung injury, and prolonged mechanical ventilation (see Chap. 16 for detailed discussion on ILD).
• Cardiovascular disease is due to sclerosis of small coronary arteries and to myocardial fibrosis. It is frequently secondary to systemic or pulmonary hypertension. The pericardium and/or myocardium may be affected.
Pericardial disease may be present in the form of acute or chronic pericarditis and pericardial effusion. Myocardial disease results in myocardial fibrosis and ischemia, cardiomegaly, or cardiomyopathy. Left ventricular diastolic dysfunction is more common than systolic dysfunction. Arrhythmias, conduction defects, and congestive heart failure are frequently seen in patients with cardiac involvement. Systemic sclerosis is an independent risk factor for acute myocardial infarction. The incidence and range of cardiac complications seen in systemic sclerosis can be gauged from a large international study involving 3656 systemic sclerosis patients [7]. The study
reported complications separately for lcSSc and dcSSc:
palpitations were seen in 22.6% of patients with lcSSc and 27.3% of dcSSc patients, conduction block in 10.4% of patients with lcSSc and 12.7% of dcSSc patients, diastolic dysfunction in 15.4% of patients with lcSSc and 16.6% of dcSSc patients, and reduced left ventricular ejection fraction in 5% of patients with lcSSc and 7.2% of dcSSc patients. Patients with clinically apparent cardiac involvement have a poor prognosis with a 5-year mortal-
ity rate of 75% [8].
• Patients may be hemodynamically unstable as a result of systemic hypertension, vasomotor instability, and subsequent intravascular volume contraction. Finally, most patients have Raynaud’s disease, and this can be exacerbated perioperatively due to exposure to cold tempera-
tures and sympathomimetic or vasopressor agents. Pulse oximetry from the finger may be unreliable.
• Gastrointestinal disease is present in up to 90% of patients, and any part of the gastrointestinal tract may be affected. The esophagus is most commonly involved. Chronic gastroesophageal reflux, esophagitis, and recurrent
strictures are seen. Frequent aspiration of gastric contents may either cause ILD or worsen pre-existing ILD. Patients may present for surgery with malnutrition secondary to gastrointestinal disease. Enteral absorption of oral medication may be delayed due to impaired motility.
Malabsorption of vitamin K may lead to coagulation disorders.
• Renal involvement as a consequence of sclerosis is usually manifest as mild proteinuria or elevated serum creatinine, which does not progress to more advanced disease. A more serious presentation, scleroderma renal
crisis, can occur in up to 5–20% of diffuse cutaneous systemic sclerosis patients [9]. Scleroderma renal crisis is defined by severe or worsening arterial hypertension and rapidly progressive renal failure. In the past, this was a common cause of death in patients with systemic sclerosis.
It is now effectively treated with angiotensin-converting enzyme (ACE) inhibitors.
• The airway can be especially challenging secondary to restricted mouth opening, temporomandibular joint fibrosis, atrophied nasal alae, and oral or nasal telangiectasias that can bleed profusely if traumatized during intubation
[2, 10].
How Should the Patient with Scleroderma
Be Evaluated Preoperatively?
Preoperative evaluation focuses on the affected organs. A his-
tory and physical examination are required to establish the
extent and severity of systemic disease. The following are
investigations for consideration preoperatively (*) or may be
available as part of routine monitoring of these patients.
Cardiac
• *ECG.
• 24-hour Holter monitoring is part of the standard cardiac
diagnostic work-up for systemic sclerosis patients and
repeat Holter monitoring has been recommended every
1–2 years even in asymptomatic patients.
• Echocardiogram is performed annually for evaluation of
systolic and diastolic dysfunction, pulmonary hyperten-
sion, and pericardial effusion [11].
• Doppler echocardiogram is performed for initial assess-
ment of pulmonary hypertension. If found, right heart
catheterization may follow.
• Tissue Doppler echocardiography may be performed to
provide a fuller extent of myocardial dysfunction in
patients with subclinical cardiac involvement [12].
• Cardiac MRI may be used for early assessment of sub-
clinical cardiac involvement [13].
• * Test for brain natriuretic peptide (BNP) or N-terminal
pro-brain natriuretic peptide (NT-ProBNP) biomarkers,
which may be elevated in LV or RV dysfunction and myo-
cardial ischemia.
Pulmonary
• *Chest radiograph if acute disease suspected.
• Arterial blood gases.
• *Spirometry.
• Pulmonary function tests are carried out every 1–2 years.
FVC, DLCO, and TLC are the most common PFT mea-
sures used to monitor the progress of pulmonary involve-
ment [14].
• Chest CT based on clinical findings.
Gastrointestinal
• *Complete blood count, electrolyte screen, liver function
tests, coagulation screenRenal
• *Serum urea and creatinine
• Estimated glomerular filtration rate (eGFR)/creatinine
clearance
• Urinary protein
• Renal artery Doppler
• Renal biopsy
What Is the Significance of the Improvement in 6-Minute Walk Test After Cardiac Rehabilitation?
○ The 6-minute walk test (6MWT) is a simple, practical evaluation of functional exercise capacity.
○ One of the strongest indications for the 6MWT is for measuring response to medical therapy and rehabilitation.
○ It is useful in patients with chronic pulmonary disease, e.g., ILD [15].
○ It needs to be conducted according to a standard set of guidelines.
• Healthy subjects walk an average of 571 +/− 90 m (range 380–782 m) .
• The minimal clinically important distance for improvement is approximately 25–50 m
Are There Any Other Tests of Functional Ability That Could Be Used for This Patient?
○ Recent evidence suggests that subjective assessment of functional capacity, e.g., metabolic equivalent score is a poor predictor of postoperative morbidity and mortality.
○ Suggested alternatives with better accuracy include cardiopulmonary exercise testing and the Duke Activity Status Index
What Medical Therapies Can We Expect to See in Patients with a Diagnosis of Systemic Sclerosis?
○ There is no curative treatment available for the underlying disease process.
○ Precipitating or aggravating factors should be stopped, e.g., smoking, vasoconstrictor drugs.
○ Medical management consists of symptomatic treatment of the various systemic manifestations, e.g., gastroesophageal reflux is treated with proton pump inhibitors, calcium channel blockers are first-line therapy for patients with Raynaud phenomenon, and ACE inhibitors are used to treat patients with scleroderma renal crisis.
○ Patients with severe or rapidly progressive disease are treated with systemic immunosuppressive therapy, e.g., methotrexate, mycophenolate, cyclophosphamide, and rituximab. The choice of agent depends on how extensive the cutaneous or visceral disease progression is, e.g., cyclophos-
phamide is usually reserved for patients with complicating ILD.
○ Glucocorticoids are sometimes used to treat systemic sclerosis complicated by ILD. A number of studies have shown benefit from a combination of cyclophosphamide and prednisone. However, there is an association between glucocorticoid therapy and scleroderma renal crisis, which has limited its use.
Is Steroid Stress Dosing Required?
○ Patients on chronic steroid therapy may develop secondary adrenal insufficiency due to suppression of the hypothalamic-pituitary-adrenal axis (HPAA).
○ Subsequent low corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) levels lead to adrenal atropy and decreased cortisol production.
○ The adrenal gland normally secretes approximately 10 mg cortisol daily.
○ Surgical stress increases adrenal output of cortisol. This varies from 50 mg/day for minor procedures to 150 mg/day for major surgery.
○ Patients on chronic steroid therapy are therefore at risk for perioperative
adrenal crisis.
○ This can be life-threatening and requires treatment with stress-dose steroids, fluid, and vasopressors.
○ Steroid stress dosing is a complex subject, and available recommendations can be confusing.
○ Administering a supplementary stress steroid dose may prevent perioperative adrenal crisis. However, this is a rare occurrence, and it must be balanced against the risk of unnecessary steroid administration.
○ A recent review by Liu et al. is helpful in this regard [23].
- The authors state that patients taking any dose of glucocorticoid for less than 3 weeks, morning doses of prednisone 5 mg/day or less, or prednisone 10 mg/day on alternate days are at low risk for HPAA suppression and do not need stress steroid dosing.
- However, those taking prednisone 20 mg/day for more than 3 weeks require a steroid stress dose.
True/False Questions
1. Concerning the clinical presentation and progression of
systemic sclerosis
(a) Women are more frequently affected
(b) Raynaud’s phenomenon is present in over 90%
patients
(c) The commonest affected organ is the kidney
(d) Pulmonary disease is the main cause of death
(e) Scleroderma renal crisis occurs in up to 20% of
patients with dcSSc
1a.T
1b.T
1c.F
1d.T
1e.T
- Preoperative evaluation and optimization
(a) An echocardiogram is indicated if one has not been performed for a year or longer
(b) Peak expiratory flow rate (PEFR) is the most useful component of PFTs for the systemic sclerosis patient
(c) Immunosuppressive therapy is curative
(d) Cyclophosphamide is a first-line treatment for systemic sclerosis and ILD
(e) ACE inhibitors have revolutionized the treatment of scleroderma renal crisis
2a.T
2b.F
2c.F
2d.T
2e.T
What Is Rheumatoid Arthritis?
○ RA is an immune-mediated inflammatory disease.
○ RA has a prevalence of ≈ 1% among Caucasians but is far more common in sub-populations (e.g., 5% in some Native American tribes).
○ A family history increases the risk of developing the disease up to fivefold.
○ The HLA-DRB1 gene is a dominant marker of risk for the development of RA.
- HLA-DRB1 encodes cell surface proteins belonging to the major histo-compatibility (MHC) class II system and are key components of the immune response system.
○ The MHC class II system presents antigens to T-lymphocytes that stimulate T-helper cells, which in turn evoke B-cells to produce anti-bodies to the presented antigen.
- Some B-cells can become autoreactive, i.e., mount an inappropriate response to host tissue.
- Immune tolerance mechanisms function at several stages of B-cell development to regulate such potentially destructive behavior.
○ It is thought that RA develops in part due to a loss of tolerance in this system in genetically predisposed individuals, perhaps initiated due to exposure to environmental factors [1].
○ There are no specific diagnostic criteria for RA; it is one of exclusion.
- The finding of serological markers such as rheumatoid factor (RF) and autoantibodies against citrullinated peptides (ACPA) are suggestive of RA.
○ The classic extra-articular manifestations of RA including vasculitis, interstitial lung disease, secondary amyloidosis, and cardiovascular disease appear to be reduced if current therapeutic algorithms are instituted early in the disease process.
○ Modern management involves ongoing assessment and disease monitoring with appropriate adjustment of the therapeutic approach to minimize immune activation and attenuate the inflammatory response.
What Is the Current Approach to Management of a Patient Presenting with RA?
○ The overarching principles underlying treatment of RA include shared decision-making between patient and rheumatologist. Treatment is based on disease activity, progression of structural damage and safety issues, and
recognition of the cost of RA both to the patient and to society.
○ Treatment guidelines suggest therapy should be initiated at time of RA diagnosis.
○ Prior to initiating treatment, patients are screened for pre-existing liver disease (including hepatitis B and C) and tuberculosis, as these conditions can be exacerbated or reactivated by RA drug therapy.
Four main classes of drug are used in the treatment
of RA:
1. Conventional synthetic disease-modifying antirheumatic drugs (DMARDs):
(a) Methotrexate
(b) Sulfasalazine
(c) Leflunomide
(d) Chloroquine
(e) Hydroxychloroquine
2. Biological disease-modifying antirheumatic drugs (bDMARDs):
(a) Tumour necrosis factor (TNF)- α inhibitors: adalimumab; golimumab; certolizumab; infliximab; etanercept
(b) IL-1 receptor antagonist: anakinra
(c) IL-6 receptor antagonist: tocilizumab
(d) Anti-CD20 monoclonal antibody: rituximab
3. Biosimilar disease-modifying antirheumatic drugs (bsD-MARDs): These are generic versions of the above biologics.
4. Targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs):
(a) Janus kinase inhibitors: Tofacitinib and baricitinib
○ The above list is not exhaustive.
○ Usual initial treatment of RA is with a conventional DMARD, usually methotrexate in combination with low dose (usually short-term) glucocorticoids.
○ Other DMARDs may be used in combination with methotrexate, although the value of this approach is controversial due to the increased risk of drug-related side effects.
○ The goal of initial treatment is to achieve 80% improvement of disease activity within 3 months of starting treatment.
○ Failure of this regime calls for the introduction of bDMARDs and thereafter tsDMARDs.
How Should These Medications RA Be Managed Perioperatively?
○ Given the forgoing, it is appropriate, time permitting, for the patient’s rheumatologist to be informed of planned surgical interventions and advice regarding RA status and perioperative management solicited.
○ A shared component of all forms of DMARDs is immunosuppression, as the goal of therapy is to reduce inflammation and inhibit joint damage.
○ DMARDs may, in theory, increase the risk of perioperative infection, particularly in the case of elective joint arthroplasty (EJA) procedures.
- Studies investigating this issue are inconclusive. However, the reality
is that perioperative infection rates in patients with immune-mediated inflammatory joint disease are greater than similar patients with osteoarthritis undergoing EJA.
- Recognizing the paucity of trial data, the College of Rheumatology and the
American Association of Hip and Knee Surgeons have jointly developed empirical best practice guidelines on how to manage DMARDs perioperatively [4].
- Key recommendations for preoperative management for RA patients undergoing EJA are as follows:
1. Continue conventional DMARDs at current dose
2. Withhold all bDMARDs/bsDMARDs preoperatively and plan surgery at the end of the dosing cycle for the specific medication
3. Withhold tofacitinib 7 days prior to surgery
4. Continue current doses of glucocorticoids (if <16 mg/day prednisone or equivalent) rather than administering supra-physiological doses (stress dosing) on the day of surgery
What Are the Extra-articular Manifestations of RA of Concern Perioperatively?
○ Patients with RA are at greater risk of suffering a stroke or myocardial infarction than the general population.
○ There are emerging data suggesting that the current treatment paradigm of using DMARDs to target the inflammatory process underlying RA in an aggressive manner may ameliorate the cardiovascular consequences of RA.
- Symptoms of isch-emic heart disease or a history of transient ischemia events should be rigorously investigated preoperatively.
○ Pulmonary nodules, fibrosing alveolitis, and decreased chest wall compliance may occu.
○ Drug-related issues and peripheral neuropathy should be documented
Should This Patient Receive “Stress Dose”
Steroid Treatment?
There is still ambiguity about the role of “stress dose” steroid
treatment during the perioperative period. An exhaustive
review of the literature by Joseph et al. [6] concludes that
there is insufficient evidence to determine the prevalence of,
time to recovery from, and influence of glucocorticoid dose
and duration on glucocorticoid-induced adrenal insuffi-
ciency. The routine administration of standard “stress dose”
steroids (typically hydrocortisone 100 mg) prior to surgery is
to be carefully considered, given the risks inherent in this
approach, which include immunosuppression, bone fracture,
and gastrointestinal hemorrhage. A simple way to assess the
integrity of the hypothalamic-pituitary-adrenal (HPA) axis is
to measure early morning cortisol levels—a patient with a
level >10 mcg/dl (275 nmol/L) is unlikely to have HPA axis
issues and suggests that the patient does not require supple-
mental steroid therapy perioperatively. This approach,
although optimal, does present practical difficulties in
obtaining the appropriate blood specimen. A thoughtful and
practical approach has been outlined by Liu et al. [7]. Under
these recommendations our patient would be considered to
be at “low” risk of HPA suppression and no “stress dose”
would be administered
What Is the Current Approach to Opioid Use
in RA?
Chronic opioid use is relatively common among RA patients,
although there is little evidence that such treatment is effica-
cious or safe [8]. It is recommended that a range of non-
pharmacological measures be considered prior to initiating
opioid therapy [9]. Opioids are best reserved for acute man-
agement of pain associated with an RA flare. Nevertheless,
many patients with RA have been taking opioids for many
years, and it is important to document this and indicate to the
patient to take their usual dose of opioid on the morning of
surgery.
Are There Any Specific Laboratory Tests That
Should Be Ordered Preoperatively
in a Patient with RA Being Treated with Any
Form of DMARD?
Patients under the care of a rheumatologist will have had
scheduled laboratory monitoring of renal, liver, and hemato-
logical function. In the absence of available data within 6
months of the date of scheduled surgery, a prudent course
would be to obtain a complete blood count, renal panel, and
baseline liver function tests. Anemia and drug-induced
thrombocytopenia and neutropenia, as well as impaired renal
and liver function, are not uncommon in patients with RA.
How Common Is Cervical Spine Disease
in the Patient with RA?
Joint and ligament destruction is the hallmark of RA, but
early and aggressive use of DMARDs and TNF-α inhibitors
may significantly impede if not halt this aspect of the dis-
ease,1 though long-term studies are lacking. However, there
are many patients who developed RA prior to the use of cur-
rent management strategies or who, for whatever reason, are
unable to access such therapy. In the latter populations, cer-
vical spine involvement by RA is undoubtedly common.
The occiput-C1 and C1-C2 joints are most prone to RA
involvement, as they are synovial joints without cushioning
discs (the latter are not affected by RA-induced inflamma-
tion) [10]. The occiput-C1 joint is a relatively stable saddle
joint, but basilar invagination can occur, so that the odontoid
process appears to enter the foramen magnum. The C1-C2
joint has horizontally orientated articulations (no bone bar-
rier to subluxation) and is supported in this plane by liga-
ments that can be significantly damaged by RA, inducing
laxity and instability [10]. It is the cervical joint most com-
monly affected by RA.
Subluxation of these joints decreases the space available
for the spinal cord and can lead to compression of the cord
and/or vertebral arteries. Subaxial subluxation, as seen in the
patient under discussion, is less common and results from
destruction of the facet and uncovertebral joints.
Patients with significant RA-induced cervical spine dis-
ease may be asymptomatic, and preoperative radiological
assessment of the cervical spine is reasonable in any patient
with significant disability and ongoing disease activity. Pain radiating to the occiput, paresthesia in the shoulders and
arms on head movement, and/or sensory loss in the derma-
tomes supplied by brachial plexus are suggestive of cervical
spine pathology and warrant radiological examination of the
cervical spine, with MRI assessment if significant pathology
is found on screening films [11].
Is Regional Anesthesia the “Best” Choice
in This Patient?
If acceptable, appropriate, and feasible, regional anesthesia
is an excellent choice for anesthetic management of the
patient with significant RA-induced pathology undergoing
surgery [12]. It is advisable to discuss the possibility of
awake fiberoptic intubation if there is any evidence of airway
compromise, as it may be difficult, if not impossible, in some
cases to perform a regional technique.
True-False Questions
1. In a patient with RA:
(a) The diagnosis is confirmed if the rheumatoid factor is
positive
(b) Early and consistent use of medication should mini-
mize joint destruction
(c) All disease-modifying drugs suppress the immune
response
(d) The subaxial cervical spine is most commonly affected by RA
(e) The risk of stroke is increased
1a.F
1b.T
1c.T
1d.F
1e.T
- In the perioperative management of a patient with RA:
(a) Methotrexate should be held for 14 days before
surgery
(b) All biological disease-modifying drugs should be
held preoperatively
(c) Liver and renal function should be assessed
(d) “Stress dose” steroids in the form of hydrocortisone
should always be ordered
(e) A cervical spine radiograph is always mandatory
2a.F
2b.T
2c.T
2d.F
2e.F
How Is SLE Diagnosed?
○ There are no definitive diagnostic criteria.
○ A diagnosis of SLE is made based on the presence of characteristic clinical
and laboratory features in the context of serologic biomarkers, e.g., antinuclear antibodies or anti-double-stranded DNA antibodies.
○ A number of classification criteria have been developed for the purposes of research and disease surveillance (Tables 30.1 and 30.2) [4–7].
○ Consensus diagnostic guidelines from the American College of Rheumatology (ACR) and the Systemic Lupus International Collaborating
Clinics (SLICC) criteria are two commonly used tools [5, 7].
○ Even though these tools were developed to ensure consistency for the purposes of research, they can be useful in clinical practice to differentiate patients with lupus-like clinical features from patients with another systemic autoimmune disease [8].
What Can Be Ascertained from This Patient’s PFTs?
- A restrictive pattern of pulmonary disease is present as evidenced by the low FVC.
- At less than 13% of predicted, this patient is considered very high risk for prolonged postoperative ventilation.
- Full PFT testing with diffusion capacity for carbon monoxide (DLCO) is indicated when a restrictive pattern is present. However, due to the low volumes attained and the patient’s BiPAP dependence, lung volume and DLCO measurement were not attempted. We know that there is no element of obstruction in this disease pattern as the FEV1/FVC pattern is normal.
- An obstructive defect is present when FEV1/FVC is less than 70%
