Tissue Disorders

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© Springer Nature Switzerland AG 2021

R. Reti, D. Findlay (eds.)Oral Board Review for Oral and Maxillofacial Surgerydoi.org/10.1007/978-3-030-48880-2_17

17. Connective Tissue Disorders

Zain Manji1  , Robert Reti2 and Damian Findlay3

Bramalea Oral Surgery, William Osler Health System, Department of Surgery, Division of Oral & Maxillofacial Surgery, Brampton, ON, Canada

Southwest Oral Surgery, St. Louis, MO, USA

Oral Facial Surgery Institute, St. Louis, MO, USA

Systemic lupus erythematosusRheumatoid arthritisObesityBody mass indexMyasthenia gravisEhlers-Danlos syndromeMarfan’s syndromeDisease-modifying antirheumatic drugs (DMARDs)Muscular dystrophy

Systemic Lupus Erythematosus (SLE)

  • A multisystem chronic inflammatory disorder characterized by autoantibody production responsible for immune-mediated tissue damage.

  • SLE is mostly seen in women of child-bearing age with the African American, Asian, and Hispanic demographic having the higher prevalence. The clinical variance in presentation and expression of the disease differs dramatically between patients. Most patients with SLE will experience remissions and exacerbations.

  • The most common symptoms are constitutional symptoms (fever, fatigue, weight gain), arthralgias, pancytopenia, photosensitive rash (e.g., malar rash/butterfly rash), and serositis.

  • Arthritis and arthralgias occur in 90% of SLE patients during the course of their disease. It may vary as mild joint pain to deformities. It usually presents as a symmetric inflammatory arthritis of the knees, wrist, or small joints of the hand.

  • Jaccoud-like arthropathy initially resembles the ones observed in rheumatoid arthritis but, classically, it is “reversible.” It is characterized by subluxation of metacarpophalangeal joints, “swan-neck” and Boutonniere deformities. Hyperextension at the interphalangeal joint of the thumb may also be present. The absence of erosions on radiography distinguishes it from those of RA. Patients do not tend to have prolonged morning stiffness.

  • It should be noted that procainamide (antiarrhythmic) is known to cause a drug-induced SLE that will resolve weeks after discontinuation.

Multisystem Manifestations of SLE

  • Renal – Renal involvement is found in the majority of SLE patients with about half of these having a significant nephritis. The most common nephropathy is immune complex-mediated glomerulonephritis, which may result in hypoalbuminemia. Oliguric renal failure may result as GFR is reduced.

  • Pulmonary – Pleuritis is the most common manifestation of SLE and occurs in up to 30% of patients sometime in the course of their disease [1]. Pleural effusions, pulmonary arterial hypertension, and chronic interstitial lung disease, although less common, may be seen. Pulmonary function tests will show a restrictive lung pattern. A chest X-ray for evaluation of pulmonary involvement is warranted in this patient population.

  • Cardiac:

    • Pericarditis occurs in 50% of patients with SLE, although usually small and asymptomatic, found mostly at time of autopsy or coincidental finding on imaging [2]. It may manifest itself as substernal chest pain with relief of symptoms while bending forward and exacerbated on inspiration.

    • Libman-Sacks endocarditis (aka verrucous endocarditis) has been recognized as a characteristic valvular abnormality in SLE. The pea size granular lesions normally involve the posterior leaflet of the mitral valve, although all four valves may be involved. The lesion may spread to the endocardium causing regurgitation. Advanced atherosclerosis is prevalent in SLE patients.

    • Patients are more prone to cardiac arrhythmias.

    • Hydroxychloroquine is known to cause a prolonged QT interval.

  • Maxillofacial – The cutaneous and mucous membranes are commonly affected. The oral cavity may have lichenoid lesions, nondescript erythematous patches, or granulomatous lesions. These lesions commonly are found on the buccal mucosa or the hard palate. Involvement of the lower lip may show lupus cheilitis, which involves the vermillion of the lower lip. The characteristic butterfly facial rash with nasolabial fold sparing is the classic rash of SLE (seen in up to 60% of patients) [1].

  • Hematology – All three blood cell lines can be affected. Anemia of chronic disease is commonly seen, and it is a normochromic, normocytic anemia with low serum iron and lower transferrin. Hemolytic and aplastic anemia may be present. Leukopenia and thrombocytopenia are seen in about half of SLE patients. Patients with SLE are at a higher risk of thromboembolism due to the presence of antiphospholipid antibodies/syndrome.

  • Neuropsychiatric – Patients have neuropsychiatric manifestations as a result of inflammation. Manifestations include an acute confusional state, seizures, mood disorders, psychosis, aseptic meningitis, optic neuritis, and central and peripheral neuropathies.


  • Diagnosis is based on a constellation of symptoms and not serological testing alone. It should be noted that more than 50% of SLE patients will not have met four criteria at one time, but will have during the course of their disease. ANA is the most common specific antibody found in SLE, but anti-DSDNA and anti-Sm are more specific. The American College of Rheumatology requires four or more of the criteria met and exclusion of other reasonable diagnosis [3].

  • DOPAMINE RASH is a mnemonic for SLE.

    • Discoid rash

    • Oral ulcers

    • Photosensitivity

    • Arthritis > 2 joints

    • Malar rash

    • Immunologic criteria: anti-Sm Ab, anti-DSDNA

    • Neurologic symptoms: seizures, psychosis

    • ESR elevated

    • Renal disease

    • ANA positive

    • Serositis: pleurisy, pericarditis

    • Hematologic disorders: hemolytic anemia, leukopenia, thrombocytopenia


  • NSAIDs can often control arthritis and serositis. Patients are to avoid sun exposure due to photosensitivity.

  • Corticosteroids should be limited to treat acute or subacute symptomatology but are effective at managing thrombocytopenia and hemolytic anemia as well as suppressing glomerulonephritis and cardiovascular abnormalities. Topical steroids can be used to treat cutaneous and mucosal lesions. Hypoadrenalism and emotional disturbances can be major side effects. Heavy use of corticosteroids in treating SLE patients may lead to early-onset osteoporosis.

  • Antimalarial drugs such as hydroxychloroquine (Plaquenil®) are used long term to control disease flare-ups. Long-term use, greater than 400 mg daily, can lead to eye toxicity and should be monitored every 6–12 months.

  • Severe disease symptoms require immunosuppressant agents such as alkylating agents (e.g., cyclophosphamide), purine synthesis inhibitors (e.g., azathioprine), and disease-modifying agents such as methotrexate (folate agonist). Consider biologic agents (e.g., rituximab, belimumab) for refractory cases.

Patient Management

  • Consult with patient’s rheumatologist.

  • Elective surgery should be deferred until flare-ups have resolved.

  • Preoperative laboratories: CBC, aPTT, and BMP.

    • Rule out anemia, thrombocytopenia, coagulopathies, renal compromise, and electrolyte disturbances.

  • EKG to rule out ischemic heart disease and rhythm disturbances.

  • Auscultation to assess for cardiac murmurs and pulmonary involvement.

  • Consider supplemental antibiotics in the setting of immunosuppression [3].

  • Consider steroid supplementation for adrenal suppression.

  • Avoid nephrotoxic drugs. Also, maintain urine output by avoiding hypotension and hypoperfusion.

  • Airway considerations include mild laryngeal inflammation, vocal cord paralysis, subglottic stenosis, and laryngeal edema with acute obstruction may be seen in SLE which may make intubation and extubation difficult [3].

  • Patients may be anticoagulated due to hypercoagulable state and should be managed appropriately.

Rheumatoid Arthritis (RA)

  • A chronic systemic inflammatory disease of unknown etiology characterized by inflammatory polyarthritis (synovitis) with progressive destruction of joint, bone, and articular cartilage.

  • RA affects females more than males (3:1).

  • It usually affects patients in the fifth to sixth decade of life.

  • It is a symmetrical polyarthropathy and the joints involved tend to be warm to the touch. Morning stiffness and swelling of the joints involved over 1 hour are hallmark signs of RA.

  • Classic features are ulnar deviation and subluxation of the metacarpophalangeal joints, the swan-neck deformity (hyperextension of the proximal interphalangeal joint), and Boutonnière (hyperflexion proximal interphalangeal joint) deformities (See Fig. 17.1). This differs from osteoarthritis, which involves weight-bearing joints. Other major joints normally involved are the wrists, knees, elbows, ankles, and hips.

  • Rheumatoid nodules are present in 1/5th of patients with RA. They are non-painful, firm, and normally present on the extensor surface of the forearms, but can be anywhere.

  • The cervical spine is commonly involved, most often a C1–C2 (atlantoaxial) subluxation. When separation is severe, the odontoid process can exert pressure on the spinal cord and impair blood flow through the vertebral arteries. The deformity can be easily observed on a lateral plain film of the cervical spine of which up to of 3 mm or more gap can be seen between the anterior margin of the odontoid process from the posterior margin of the anterior arch of the atlas. Limitation of neck extension should be practiced with SLE patients to demonstrate range of motion to avoid damage to the spinal cord.

Fig. 17.1

Hand deformities seen in RA. (Modified from Rahman and Giles [17])

Multisystem Manifestations of RA

  • Cardiovascular – In the cardiovascular system, pericarditis, myocarditis, CAD, aortitis with aortic dilatation leading to a possible aortic regurgitation and advanced atherosclerosis may be present.

  • Ocular – Eye pain and redness due to keratitis, scleritis, and episcleritis; foreign body and dryness sensation with keratoconjunctivitis and sicca. If severe enough, visual acuity can be compromised.

  • Neurological – Neuropathy secondary to deposition of complexes into the vaso nervosum.

  • Pulmonary – In the pulmonary system, pleural effusions and rheumatoid nodules may develop. If the costochondral joints are involved, this may create a restrictive lung disease pattern due to restricted wall movement. Preoperative pulmonary function studies may be indicated for those with advanced disease.

  • Hematological – Anemia of chronic disease may be seen. Felty’s syndrome (RA with splenomegaly and leukopenia) may occur. Small vessel vasculitis may manifest as digital infarcts and represent a poorly controlled state of the disease.


  • Not based solely on lab results. Common lab findings include rheumatoid factor titers increased, elevated erythrocyte sedimentation rate, and elevated C-reactive protein.

  • Diagnostic Criteria for Rheumatoid Arthritis (symptoms must be >6 weeks & 4/7 criteria must be met):

    • Morning stiffness (≥1 hour).

    • Swelling of 3+ joints.

    • Swelling of hand joints.

    • Symmetrical swelling.

    • Subcutaneous nodules.

    • Serum rheumatoid factor.

    • Radiographic evidence of erosive arthritis.


  • Treatment of the disease may include anti-inflammatory drugs like corticosteroids (e.g., prednisone) to decrease swelling and stiffness. Long-term use can lead to osteoporosis, poor wound healing, adrenal suppression, and hyperglycemia.

  • Disease-modifying antirheumatic drugs (DMARDs) are used to slow and halt progression of the disease. They include methotrexate, hydroxychloroquine (Plaquenil®), antimalarials, minocycline, and tofacitinib (Xelijanz®).

  • The preferred medication methotrexate acts by inhibiting metabolism of folic acid via dihydrofolate reductase. Close monitoring is required to monitor for liver dysfunction and bone marrow suppression.

  • Hydroxychloroquine requires yearly eye exams to rule out macular toxicity.

  • Monoclonal antibody biologics – entanercept (Enbrel®), infliximab (Remicade®), and Adalimumab (Humira®) work by inhibiting TNF-α.

Patient Management

  • Preoperative laboratories: CBC and BMP.

    • Rule out anemia, thrombocytopenia, renal compromise, and electrolyte disturbances.

  • EKG to rule out ischemic heart disease.

  • Cardiopulmonary exam to assess for cardiac murmurs and pulmonary involvement.

  • Consider PFTs if there is presence of restrictive lung disease.

  • Consider supplemental antibiotics in the setting of immunosuppression.

  • Consider steroid supplementation for adrenal suppression.

  • Avoid nephrotoxic drugs.

  • Intubation considerations:

    • Hoarseness or stridor in this patient group may be a sign of cricoarytenoid joint involvement, which limits glottic opening making intubation difficult.

    • Additionally, TMJ involvement with limitation of opening should be identified before any anesthesia delivered.

    • Flexion deformity of the cervical spine may make intubation difficult due to difficulty with extension.

    • Atlantoaxial subluxation should be confirmed preoperatively with a radiograph. When present, care must be taken to when extending the neck during laryngoscopy to prevent spinal cord damage.

Osteoarthritis (OA)

  • A painful degenerative process involving progressive deterioration of articular cartilage and remodeling of subchondral bone that is not primarily inflammatory.

  • OA effects females to male 2:1 and occurs predominately later in life at ages 50 and above [4].

  • Risk factors are age, female gender (especially post-menopausal), obesity, smoking, trauma from physical activity, occupation of physical nature, and muscle weakness.

  • The hallmark of osteoarthritis is damage to articular cartilage. Cartilage normally distributes loads across joint surfaces to aid in smooth movement.

  • Changes in the cartilage progresses through roughness, fibrillation, fissuring, and eventual erosion of the cartilage. The erosive process activates chondrocytes to release proteolytic enzymes causing further degeneration. The unprotected bone underlying the articular cartilage (subchondral bone) results in thinning (attrition) leading to subchondral cysts early on and later to subchondral sclerosis as bone formation is outpaced by bone resorption.

  • The large weight-bearing joints (knees and hips) are the most commonly affected.

  • Symptoms are prominently aching and pain that is worse with function. Morning pain is normally brief (less than 30 minutes). Joint instability, locking, sensation of grinding, and limited range of motion are common findings.

  • Small joints of the hands are the most commonly affected. Osteophytes of the distal interphalangeal joints (Heberden nodes) or the proximal interphalangeal joints (Bouchard’s nodes) can lead to visible and palpable nodes.

  • Common radiographic findings are joint space narrowing, subchondral sclerosis, and osteophytes.

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Jul 23, 2021 | Posted by in Oral and Maxillofacial Surgery | Comments Off on Tissue Disorders
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