Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

CHAPTER 10 – Skin and Bone Disorders

John E. Tetzlaff, MD



Achondroplasia and Dwarfism



Behçet's Disease



Epidermolysis Bullosa



Erythema Multiforme



Erythema Nodosum



Fabry's Disease



Herpes Simplex












Osteogenesis Imperfecta



Osteoporosis, Osteomalacia, and Osteopetrosis



Paget's Disease of Bone






Pemphigus and Pemphigoid






Pyoderma Gangrenosum

In this chapter a discussion is presented of the diseases and syndromes that involve the skin and bones in the context of the perioperative period. The goal is to define the anesthetic issues, including preoperative preparation, intraoperative management, and postoperative care.

Skin and bone disorders have in common alteration of the surface of the body. As a consequence, anesthetic care can be challenging. Airway management can be difficult if the anatomy is abnormal. Regional anesthesia can also be difficult or impossible for the same reason. Alterations in surface anatomy present difficult issues for positioning, and routine movement of the patient can cause significant skin lesions or bone fracture. Some of these diseases are associated with comorbidity that must be investigated preoperatively and taken into account in the perioperative care. Some of these diseases are chronic and controlled with a variety of medications that can cause organ toxicity. This knowledge will alter preoperative preparation of these patients. When these diseases create the indication for surgery, particularly urgent surgery, knowledge of the pathophysiology can guide management and decrease the risk of morbidity.



The chondrodysplasias are a group of related syndromes associated with abnormality of the size of the trunk, limbs, and skull, resulting in a disproportionate shortness of stature. Achondroplasia is the most common form of dwarfism.[1] The pathophysiology is abnormal cartilage formation, particularly at the epiphyseal growth plates.[2] Cellular structure of individual cartilage cells is abnormal.[3]Classification is based on the site of the dysplasia (e.g., epiphyseal, metaphyseal, and diaphyseal).[4] Other terms to name these diseases include “spondylo” for those that affect the spine, and “cranio” for those that involve the base of the skull. Further classification is based on age at onset (infantile) and genetic inheritance (X-linked, recessive, or autosomal dominant). The etiology is unknown but has been associated with numerous causative factors.[2]

Differential Diagnosis.

Another name for achondroplasia is short-limbed dwarfism. The achondroplastic appearance is an adult less than 4 feet tall, with a large head, bulging forehead, depressed nasal bridge, prominent mandible, and short arms and legs with normal trunk size. In those that survive infancy, life expectancy is normal. Infants with this condition have shortening of the proximal part of the limbs, protuberance of the frontal skull, and depressed nasal bridge, related to shortness of the base of the skull. Lordosis, thoracolumbar kyphosis, and pelvic narrowing are present, and severe spinal stenosis is common.[1] Spinal stenosis can manifest as nerve root compression, cauda equina syndrome, thoracolumbar spinal cord compression, or high cervical cord compression due to stenosis of the foramen magnum. Quadriplegia has been reported in an achondroplastic infant due to stenosis of the foramen magnum caused by normal range of motion.[5] Atlantoaxial dislocation also caused high cord compromise in another infant.[6]Quadriplegia occurred after anesthesia and surgery in a diastrophic dwarf with severe kyphosis.[7]

Achondroplasia is an autosomal dominant syndrome, although family history is less obvious because fertility is low.[8] Other genetic information is contained in Table 10-1 . The differential diagnosis of short stature (dwarfism) is based on a combination of clinical and radiographic features. Numerous comorbidities are associated with these syndromes and are listed in Table 10-2 .

TABLE 10-1   -- Chondroplasia: Genetic


Clinical Issues



Limbs, skull, spine

Autosomal dominant

Dystrophic dysplasia

Limbs, spine, cleft palate




Autosomal dominant

Metaphyseal dysplasia



Spondyloepiphyseal dysplasia

Spine, cleft palate

X-linked recessive



TABLE 10-2   -- Comorbidities Associated with Achondroplasia and the Chondrodysplasias



Malformation of the skull






Dental abnormalities



Mental retardation



Seizure disorder






Atlantoaxial instability (hypoplastic odontoid)



Scoliosis, kyphosis



Spinal stenosis



Difficult airway criteria



Congenital heart disease



Obstructive sleep apnea



Pulmonary hypertension



Cleft palate






Preoperative Preparation ( Table 10-3 )

Because of the associated congenital defects, abnormalities of the cardiovascular and respiratory systems should be actively evaluated in all patients with chondrodysplasia. Chest radiography, electrocardiography, and transthoracic echocardiogram are minimum requirements. A difficult airway will be present in a majority, complicated further by anatomic abnormality of the skull, neck, and chest. Cleft lip, cleft palate, and micrognathia may also contribute to difficult airway management. Stridor can occur spontaneously, secondary to laryngomalacia.[9] Symptomatic subglottic stenosis, requiring urgent tracheostomy for emergency surgery, has been reported.[10] The potential for atlantoaxial instability from abnormal odontoid development[1] or congenital absence of the odontoid[11] should be investigated with flexion-extension lateral cervical spine radiographs and open mouth view of the odontoid. If inconclusive, magnetic resonance imaging (MRI) of the skull and cervical spine is required. When there are cervical radicular signs or if mental retardation makes recognition impossible, high cervical stenosis should be assumed and delineated with computed tomography (CT) or MRI. When spinal cord compression is identified, decompressive laminectomy or decompression of the foramen magnum is indicated. Kyphoscoliosis can be severe, and evaluation of pulmonary reserves with chest radiography, arterial blood gas analysis, and pulmonary function tests may be required. Thoracic dystrophy can be associated with some rare dwarfism syndromes and can greatly exaggerate the ventilatory compromise with kyphoscoliosis owing to mechanical restriction of thoracic excursion. Tracheomalacia is one additional source of airway compromise and should be actively sought by identification of symptoms, CT, or flow-volume loops. Because of the shape of the head and neck, obstructive sleep apnea will be present in as many as 40% of achondroplastic patients, even in childhood. [12] [13] Central sleep apnea has been reported in patients with high cervical spinal stenosis or stenosis of the foramen magnum.[13] Because there is no specific treatment for achondroplasia, there are no recurring medications. Any medication list would be related to comorbidities, such as seizure disorder or lung disease.

TABLE 10-3   -- Preoperative Issues for Achondroplasia Patients



Anticipated difficult airway






Cervical spine instability






Obstructive sleep apnea



Abnormal chest mechanisms



Intraoperative Considerations.

The primary concern in achondroplasia relates to airway management. The high probability of encountering a difficult airway makes preparation for awake intubation options necessary. Reduced endotracheal tube size has been recommended.[14] Urgent airway management should be avoided because atlantoaxial instability or spinal canal stenosis puts the cervical spinal cord at risk with traditional airway maneuvers. Laryngeal mask airway (LMA) has been reported as a means to achieve oxygenation and to facilitate endotracheal intubation when it is otherwise impossible in these infants.[15] High spinal cord injury and death have been reported after routine airway management (neckflexion, extension of the occiput) in patients with atlantoaxial instability. Ventilatory difficulty should be assumed; and because of restrictive pulmonary disease, general anesthesia may be impossible without tracheal intubation. Mechanical ventilation may require a high respiratory rate and a reduced tidal volume. Volume ventilation may need to be abandoned for pressure-control ventilation.

All forms of general and regional anesthesia have been performed in patients with achondroplasia ( Table 10-4 ). Spinal surgery, especially of the cervical spine, may require evoked potential motoring (somatosensory, motor), which modifies anesthetic options. Regional anesthesia has been reported for achondroplastic patients. Spinal and epidural anesthesia for surgery [16] [17] [18] and obstetrics [19] [20] [21] [22] [23] have been reported as successful, although technically difficult. Successful combined spinal/epidural anesthesia has also been reported.[24] Emergency cesarean section has been accomplished with spinal anesthesia when the issues of a difficult airway were obvious.[25] Extensive spread of small volumes of local anesthetic in the epidural space has been reported and could lead to dangerously high block if reduced volumes are not administered.[26] Peripheral nerve block and plexus block have been accomplished without incident; however, there is concern for the uncontrolled airway management issues that occur with local anesthetic induced seizure activity. The use of ketamine, succinylcholine, and nitrous oxide for cesarean section has been reported for a full-term achondroplastic parturient who requires general anesthesia.[27] Because of the anatomic and functional abnormality of the thoracic spine, ribs, and chest, postoperative ventilatory insufficiency may occur, and extended mechanical ventilation may be necessary. The high probability of obstructive sleep apnea[12] will make postoperative pain management challenging.

TABLE 10-4   -- Anesthetic Management Issues for Achondroplasia Patients



Airway management issues



Difficult ventilation



Cervical spinal cord compression



Cervical spine instability



Technical difficulty with neuraxial block



Extensive spread of neuraxial local anesthetic



Prolonged postoperative respiratory insufficiency



Difficult acute pain control due to obstructive sleep apnea




Achondroplasia and other dwarfism syndromes are genetic congenital defects in the development of bones. They present as short stature and a variety of skeletal anomalies. Other associated congenital defects include congenital heart disease, cleft lip/palate, scoliosis, and clubfoot. Anesthetic management is complicated by difficult airway issues, spine abnormalities, including atlantoaxial instability, and cardiopulmonary compromise. Prolonged mechanical ventilation may be necessary.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


Behçet's disease is an autoimmune disease manifesting as iritis[28] and ulceration of the oropharynx, perineum, and genitalia.[29] Sporadic cases involve the central nervous system (CNS), cardiovascular system, lungs, and synovial surfaces. [30] [31] Less common lesions can occur in the urogenital and gastrointestinal tract. In some, fibrinolysis is impaired and recurrent thrombophlebitis and hypercoagulability can occur.

Differential Diagnosis and Clinical Manifestations ( Table 10-5 )

Prior to diagnosis, Behçet's disease is often confused with its numerous manifestations, defined by the major involved organ system. Skin lesions are easily confused with numerous other dermatologic diseases. Mucosal lesions are more specific, especially when the triad of iritis and oropharyngeal, and genital mucosal lesions is present.[32] When the CNS is involved, [33] [34] serious manifestations include lesions of the spinal cord, cauda equina syndrome, aseptic meningitis, seizures, dementia, coma, and intracranial thrombosis. Dural sinus thrombosis has been reported in a patient with Behçet's disease.[35] Cardiovascular manifestations include myocarditis vasculitis,[36] pericardial effusion, valve lesions,[37] arterial occlusion, aneurysm,[38] or dissection of major blood vessels.[39] Obstruction of the superior vena cava has been reported,[40] as well as other lesions of major venous structures.[41] Pulmonary manifestations [42] [43] include chronic obstructive pulmonary disease (COPD),[44]hemoptysis, bronchiectasis, pulmonary artery thrombosis, and pulmonary hypertension.[45] Glomerular lesions can precipitate chronic renal failure.[46] In patients with Behçet's involvement of the gastrointestinal tract, return of gastrointestinal function may be delayed after surgery.[47] This should also be considered in regard to drug absorbance, which can be delayed postoperatively.[48]

TABLE 10-5   -- Clinical Manifestations of Behçet's Disease



Mucosal lesions



Spinal cord lesions



Cauda equina syndrome



Aseptic meningitis






Intracranial thrombosis






Pericardial effusion



Large vessel aneurysm or dissection



Hemoptysis, bronchiectasis



Pulmonary hypertension



Chronic renal failure



Preoperative Preparation ( Table 10-6 )

When Behçet's disease presents as major organ system involvement, these systems should be completely investigated before elective surgery. Severe neurologic manifestations[49] have usually been defined at diagnosis with MRI or CT and should be reviewed for anesthetic issues (cord compression, increased intracranial pressure [ICP], or risk of herniation). If symptoms have increased since the last study, the studies may need to be repeated. Electrocardiography and echocardiography are often needed because of the cardiovascular involvement.[50] If there are significant respiratory symptoms, arterial blood gas analysis, spirometry, and a chest radiograph should be considered. Oropharyngeal ulceration can occur and become symptomatic with onset of hemorrhage.[51] If symptoms such as stridor with exertion suggest airway compromise, indirect laryngoscopy should be considered before elective anesthesia. Blood urea nitrogen/creatinine should be measured to identify or quantitate chronic renal disease and to reveal nephrotoxicity of treatment. [52] [53] [54] Because Behçet's disease is an inflammatory process, chronic use of anti-inflammatory and antineoplastic drugs is common. With chronic corticosteroid use, supplemental corticosteroids are necessary the day of surgery.

TABLE 10-6   -- Preoperative Preparation for Patients with Behçet's Disease



MRI/CT for compromised central nervous system









Pulmonary function tests



Elective evaluation of airway



Blood urea nitrogen/creatinine



Stress-dose corticosteroids



Intraoperative Considerations.

Puncture of skin or mucous membranes is very likely to result in inflammation and nodular formation and should be kept to a minimum. This would mean that regional anesthesia would be less ideal but not contraindicated. With anesthesia of the airway, topical application of local anesthetics would be preferred to airway blocks because of potential compromise of the airway from the inflammatory response to local injection.

General anesthesia can be challenging if oropharyngeal lesions are present.[55] In extreme cases, lesions can severely reduce the lumen of the oropharynx and tracheostomy might be necessary for urgent surgery. For elective procedures, awake fiberoptic intubation would be required. Use of an LMA could aggravate lesions in the airway. If spinal cord lesions are symptomatic, use of succinylcholine can result in hyperkalemia. With cervical cord lesions, intraoperative manifestations of autonomic hyperreflexia may occur.


The anesthetic implications of Behçet's disease are related to comorbidity, mainly in the CNS, cardiovascular, and pulmonary systems ( Table 10-7 ). In patients with severe oropharyngeal lesions, airway management can be difficult or impossible. Regional anesthesia can be utilized, but needle puncture may cause inflammation and lesion formation. General anesthesia is complicated by difficult airway management. There is risk of autonomic hyperreflexia if spinal cord lesions are present. If there is spinal cord involvement, the hyperkalemic response to succinylcholine can be exaggerated.

TABLE 10-7   -- Anesthetic Management Issues for Patients with Behçet's Disease



Minimize skin puncture



Difficult airway management



Difficult ventilation



Lesions from needle used for regional anesthesia



Hyperkalemia with succinylcholine



Autonomic hyperreflexia



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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


Epidermolysis bullosa (EB) is a hereditary disorder of the skin and mucous membranes that causes the development of blistering of body surfaces in response to minimal trauma. The most visible abnormalities are vesicles and bullae within skin and/or mucous membranes. Abnormal healing of these lesions is a common feature, as is contracted scarring and erosion. Although skin surfaces are the primary sites of involvement, the mucous membranes of the upper gastrointestinal tract can also be extensively involved. There are several genetic variants of epidermolysis bullosa ( Table 10-8 ).

TABLE 10-8   -- Genetics of Epidermolysis Bullosa Variants


Genetic Transmission

Epidermolysis bullosa simplex (EBS)

Autosomal dominant

Junctional epidermolysis bullosa (JEB)

Autosomal recessive

Dystrophic epidermolysis bullosa (DEB)




Epidermolysis bullosa results from defects in the structural integrity of the dermal-epidermal basement membrane. In epidermolysis bullosa simplex (EBS) there is a true split through the cytoplasm of basal cells. In junctional epidermolysis bullosa (JEB) and dystrophic epidermolysis bullosa (DEB), the defect is a lack of adherence between cellular layers. Regardless, the result is a surface structure with minimal ability to withstand any shear forces. The genetic basis is probably related to abnormal gene function for keratins.

In EBS, the presentation is obvious early in life, usually when the infant begins to crawl. Sites of maximum friction are the most symptomatic (e.g., knees, elbows). JEB and DEB present later in life, because more trauma is required to elicit the abnormal response. In some of the variants, lesions can include the anus, genitourinary tract, and, ominously from the anesthesiology perspective, the larynx and vocal apparatus. Laryngeal scarring with vocal cord dysfunction or airway obstruction has been reported.[56] In EB patients, lesions of the airway can result from vigorous laryngoscopy. Esophageal obstruction and webbing has been reported.[57] Abnormality in coagulation has also been reported.[58]


Epidermolysis bullosa is not subtle, and elective surgery in severe cases is uncommon. Although all surface areas are at risk, each EB patient will have areas of the body more affected than others. These sites should be identified preoperatively so that they can be protected in the perioperative period. It is particularly important to identify lesions in the oropharynx or esophagus, because these may predict laryngeal involvement and risk of acute postoperative airway compromise from lesions. Fortunately, other congenital issues are not regularly associated with EB.

Preoperative Preparation ( Table 10-9 )

Most EB patients take chronic corticosteroids and need “stress-dose” corticosteroids on the day of surgery. Wound care and infection management/prevention are key elements for survival in EB patients and must be continued carefully in the perioperative period. EB patients with involvement of the esophagus may have severe dysphasia that can compromise airway reflexes and increase the risk of aspiration during induction or emergence from anesthesia.[59] Significant laryngeal stenosis has been reported with EB.[56] If history or symptomatology suggests an abnormal airway, a preoperative assessment with indirect laryngoscopy by an otolaryngologist may be necessary to identify existing lesions that could influence subsequent plans for airway management. Nephrotoxic and hepatotoxic agents such as cyclosporine and colchicine [60] [61] have been used for treatment of EB, and preoperative preparation should address these risks when they apply.

TABLE 10-9   -- Preoperative Preparation for Patients with Epidermolysis Bullosa



Stress-dose corticosteroids



Wound care



Aspiration prophylaxis



Liver function tests



Blood urea nitrogen/creatinine



Intraoperative Care.

The key to safe anesthetic care in these patients is caution with skin and mucous membranes. The blood pressure cuff should be applied over padding and only inflated when needed. Excessive pressure or sustained inflation can cause injury and should be avoided. Placement of monitors must be done with caution. [62] [63] Electrocardiographic (ECG) electrode pads can cause lesions. All positioning and patient transfers must be performed with the absolute minimum shear force applied to the body surface, and whenever possible patients should be encouraged to move themselves to decrease the risk of skin injury.[64] Spinal anesthesia for surgery has been reported.[62] Regional anesthesia for surgery or obstetrics[65] can be an excellent choice, as long as the skin at the block site is normal. [66] [67] [68] [69]Successful brachial plexus anesthesia has also been reported in EB patients.[70] Aggressive volume or injecting pressure for infiltration should be avoided, because this can cause skin lesions. With general anesthesia, airway management can be problematic.[71] Prolonged mask ventilation could subject the face to enough friction to cause disfiguring facial lesions.[72] The physical maneuvers necessary to properly place an LMA would be likely to create lesions in the airway and should probably be avoided. Endotracheal intubation is the best approach to securing the airway but has been associated with lesions, edema, and hemorrhage.[73] This is particularly true with emergency obstetric care.[74] Atraumatic technique, the smallest possible endotracheal tube, and generous lubrication of the tube are necessary. There are no particular advantages among general anesthetic agents. Intramuscular and intravenous ketamine have been used as sole anesthesia for minor procedures.[75] The eyes should not be taped closed, but lubricated. The risk to skin surfaces from stormy emergence make rapid emergence techniques valuable. Suctioning during emergence should be gentle and limited to direct vision to avoid creating oropharyngeal lesions.[76] With intravenous drugs, the patency of intravenous access must be continuously verified, because extravasation can be associated with serious skin injury.

Summary ( Table 10-10 ).

Epidermolysis bullosa is a genetic defect in the skin and mucous membranes that decreases the tensile strength of body surfaces and results in extensive lesions from minimal trauma. Involvement of the esophagus and oropharynx can make airway management difficult, and even minimal trauma from laryngoscopy, stylettes, forceful intubation, or blind suctioning can create lesions that compromise the airway. Regional anesthesia can be selected, as long as the block site is clear of lesions. Excessive volume and/or pressure with infiltration of local anesthetic for intravenous placement or nerve block can cause skin injury. Intravenous extravasation is also associated with potential skin slough.

TABLE 10-10   -- Anesthetic Management Issues with Epidermolysis Bullosa



Padding pressure points



Careful patient transfer to avoid skin injury



Avoid high subcutaneous injection pressure



Injury from prolonged mask ventilation



Airway injury from instrumentation, stormy emergence



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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


Erythema multiforme (EM) is a spectrum of diseases that have in common an immunologic basis for inflammatory lesions of the skin. [77] [78] [79] When involving mainly mucous membranes, it is called the Stevens-Johnson syndrome (SJS).[80] When precipitated by a bacterial skin infection it is called the staphylococcal scalded skin syndrome (SSSS). When there is a sudden onset and a large area of skin and mucous membranes is involved, the syndrome is referred to as toxic epidermal necrolysis (TEN).[81]

Pathophysiology and Clinical Manifestations ( Table 10-11 ).

The majority of the immune reactions causative for EM are triggered by systemic virus exposure, with drugs [82] [83] and bacteria [84] [85] causing a minority of cases.[86] Some cases have been triggered by human immunodeficiency virus (HIV)[87] or herpes. Rarely, a response that resembles EM[88] can follow radiation therapy.[89] Both the bacterially triggered (SSSS, TEN) and drug triggered (SJS) types have a more abrupt onset and fulminant course.[80] Mucocutaneous lesions of the skin adjacent to the airway and mucous membranes within the airway can cause life-threatening airway compromise. In the less-fulminant EM cases, extensive skin lesions can present in a manner indistinguishable from epidermolysis bullosa. Conjunctivitis, corneal lesions, and uveitis are common. Acute myocarditis has been associated with EM triggered by viremia. Mucosal lesions of the trachea or gastrointestinal tract can cause perforation,[90] resulting in esophageal rupture, mediastinitis, pneumothorax, bronchopleural fistula, or massive gastrointestinal hemorrhage. Fulminant cases may cause acute renal failure.[91]

TABLE 10-11   -- Spectrum of Erythema Multiforme



Stevens-Johnson Syndrome (SJS)



Mucous membranes



Drug Reaction



Sudden Onset, Fulminant Course



Staphylococcal Scalded Skin Syndrome (SSSS)



Skin lesions



Bacterial trigger



Sudden onset, fulminant course



Toxic Epidermal Necrolysis (TEN)



Large lesions of skin and mucous membranes



Bacterial trigger



Sudden onset, fulminant course



Erythema Multiforme (EM)



Skin, mucous membrane



Conjunctivitis, uveitis



Corneal lesions



Renal failure



Gradual onset



Variable severity



Preoperative Preparation ( Table 10-12 ).

Mild cases of EM present no unique issues for anesthesiology or surgery. In contrast, SJS, TEN, and SSSS are phenomena that can create the need for anesthetic intervention.[92] Numerous drugs, including antimicrobials,[93] antiepileptics,[94] and antihypertensives have been reported as triggers for life-threatening airway compromise from SJS. When time permits, identifying comorbidity may allow optimization, appropriate assessment, or planning, especially if myocarditis or renal failure is known.

TABLE 10-12   -- Perioperative Issues with Erythema Multiforme



Skin care



Stress-dose corticosteroids



Echocardiogram to detect pericardial effusion



Detection of airway lesions



Emergency airway care (Stevens-Johnson syndrome)



Hypovolemia, electrolyte abnormality (toxic epidermal






Eye care



With EM patients, chronic skin care techniques to prevent skin injury and infection are important. Continuing this skin care into the perioperative period reduces the risks of infection and sepsis. Chronic corticosteroid therapy is common, and stress-dose corticosteroids are often required in the perioperative period. When myocarditis is known or suspected, echocardiography is required to define ventricular function and quantify pericardial effusion. If airway lesions are suspected, careful indirect laryngoscopy can identify critical lesions. In fulminant cases, this is specifically avoided to prevent acute airway compromise. With extensive acute lesions, loss of fluid and electrolytes can cause hypovolemia or electrolyte disturbances that should be identified and corrected. Severe chronic cases can be associated with cachexia and malnutrition.

Anesthetic Management

There are no unique anesthetic agents or techniques indicated in these patients. Barbiturates may precipitate SJS. Skin care is a primary issue. Skin injury from minimal trauma is a risk, and all elements of patient handling must reflect concern for this issue. Because cutaneous barriers are incompetent, surfaces must be protected from contamination, because bacteremia and sepsis could be fatal.

In fulminant cases, the anesthesia care required is often airway management. With SJS especially, anesthesia care for airway management is often urgent. All elements of management of the difficult airway may be required, including tracheostomy. When EM patients present for elective surgery, regional anesthesia is appropriate, as long as the skin at the site of the block is normal. With general anesthesia, nitrous oxide should be used with caution in light of the risk of occult barotrauma. For similar reasons, maximum peak ventilatory pressures should be kept as low as possible. In fulminant cases, dehydration and electrolyte loss intraoperatively should be considered likely. Monitoring devices can injure skin, as with epidermolysis bullosa. Unexplained arrhythmia could be a sign of acute myocarditis. Ocular care should reflect the possibility of EM involvement of the eyes.


Erythema multiforme is a syndrome with a variety of presentations. Minor cases have virtually no anesthetic implications. Severe cases can present for emergency airway management. The majority of the anesthetic management issues are related to comorbidities such as dehydration, electrolyte disturbance, renal failure, myocarditis, and ocular involvement. Most anesthetic techniques are appropriate.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


Pathophysiology and Clinical Manifestations.

Erythema nodosum (EN) is an acute inflammatory reaction within skin and subcutaneous tissue.[95] The nodules are deep, painful, and red and most commonly represent a hypersensitivity reaction to prior inflammation or infection.[96] Some cases can be precipitated by acute streptococcal pharyngitis. Regional enteritis and ulcerative colitis have also been associated with erythema nodosum.[97] Numerous other associated features are listed in Table 10-13 . Less common causes include leptospirosis,[98] toxoplasmosis,[99] Q fever,[100] and sarcoid.[101] A syndrome that resembles EN has been reported as a sequela of malignancy.[102]

TABLE 10-13   -- Diseases Associated with Erythema Nodosum

Streptococcal pharyngitis

Fungal infections



Inflammatory bowel disease






Yersinia enterocolitica






In the majority of cases there is associated joint involvement, most commonly of the knees, ankles, and wrists. Permanent joint deformity is uncommon, but septic arthritis can be an indication for surgery.

Differential Diagnosis.

The lesions of EN can be confused with traumatic bruising, fat necrosis, and superficial thrombophlebitis. In contrast to other dermatologic syndromes, EN is usually associated with a short interval to full resolution (3 to 6 weeks). Secondary morbidity from EN is uncommon, unless related to complications of the lesions.

Preoperative Preparation.

Because the etiology of EN can be infectious, presurgical preparation should focus on identification and treatment of the infectious etiology. In cases that present for emergent surgery (e.g., infectious arthritis), the possibility of other infections should be considered, even while not delaying the surgical procedure. When the precipitating factor is sarcoid, chest radiography and spirometry should be obtained to identify limited pulmonary reserves. Arterial blood gas analysis may be indicated for severe cases. Because viremia can be etiologic for EN, other serious sequelae of viremia, such as encephalitis and myocarditis, should be considered during preparation for emergency surgery.

Intraoperative Considerations ( Table 10-14 ).

If respiratory or systemic infections are etiologic, contamination of anesthesia equipment should be prevented with either filters or a disposable circuit/carbon dioxide absorber. Both regional and general anesthesia are possible, and there are no specific recommendations regarding agents. During acute infection, there can be coincident infection of the airway that can create issues such as laryngospasm, bronchospasm, or atelectatic lobar collapse from inspissated secretion.

TABLE 10-14   -- Perioperative Issues with Erythema Nodosum



Identify infectious etiology



Quantify diminished pulmonary reserve



Detect myocarditis, encephalitis



Prevent contamination of anesthesia gear













Erythema nodosum is a cutaneous hypersensitivity response to a variety of infectious and inflammatory disorders. Because joint involvement can occur, septic arthritis can present as an urgent indication for surgery. When sarcoidosis or pulmonary tuberculosis is causative, pulmonary compromise should be suspected. Because of the possibly infectious etiology, anesthesia equipment should be protected. There are no specific anesthetic agents or techniques either indicated or contraindicated.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier



Fabry's disease results from a congenital defect of glycosphingolipid caused by abnormal function of the enzyme alpha galactosidase A. The defect is transmitted as an X-linked autosomal recessive syndrome. The result is widespread deposition of neutral glycosphingolipids within most visceral structures and body fluids. The organs most affected are the vascular endothelium, smooth muscle of the cardiovascular and renal systems, cornea, kidney, reticuloendothelial system, and the ganglion and perineural cells of the nervous system.

Clinical Manifestations ( Table 10-15 ).

The consequences of lipid accumulation include excruciating pain, blue-black vascular lesions of the superficial layers of skin and mucous membranes, as well as organ dysfunction. The lesions of the mucous membranes commonly occur in the mouth and oropharynx. Some cases can occur without surface lesions.[103]

TABLE 10-15   -- Clinical Manifestations of Fabry's Disease



Skin lesions



Mucous membrane lesions



Coronary artery disease






Cardiac conduction lesions



Valvular heart disease



Congestive heart failure



Hypertrophic cardiomyopathy



Pulmonary hypertension



Chronic renal failure



Delayed gastric emptying



Central hyperthermia



Ocular lesions



Retinal detachment/thrombosis



The affected organ systems present with symptoms of organ dysfunction. Cardiac disease presents early in life, [104] [105] including coronary artery disease,[106] myocarditis, left ventricular hypertrophy, conduction abnormalities,[107] valvular insufficiency, [108] [109] [110] and congestive heart failure (CHF). The progress and severity of these diseases are accelerated by the universal presence of severe hypertension. Hypertrophic cardiomyopathy has been associated with some cases of Fabry's disease. [111] [112] [113] Pulmonary hypertension from lipid accumulation in the pulmonary vasculature can occur.[114] [115]

Accumulation of lipid in the kidney causes progressive loss of renal tubular units.[116] Tubules lose squamous tissue as well as the ability to exchange electrolytes. Renal blood vessels are also involved with progressive luminal narrowing. The result is progressive, chronic renal failure, and a renovascular component for hypertension. Intestinal dysfunction can occur with obstruction and delayed gastric emptying. [107] [117]

Vascular lesions occur within the CNS and peripheral nervous system. Pain, hyperhidrosis, and gastrointestinal symptoms can result. Episodic fever is reported. Abnormality in the brain stem and cerebellum cause disequilibrium and abnormal temperature regulation.[118] Dementia, seizure disorder, and intracranial hemorrhage can occur. Ocular involvement [119] [120] includes corneal opacity, lens involvement, and arterial lesions that can result in retinal artery thrombosis [121] [122] and retinal detachment.


In affected males, the diagnosis is made in childhood from skin lesions and fever of unknown origin. It can be mistakenly attributed to collagen vascular disease, rheumatic fever, or vasculitis. Fabry's disease can be diagnosed in the workup of early onset of cardiovascular, renal, or neurologic disease. Biochemical investigation is confirmatory.

Preoperative Considerations ( Table 10-16 ).

Because there is no specific treatment for Fabry's disease, preoperative preparation should focus on detection of end-organ disease. Quantification of ocular involvement should be considered to avoid the association of postoperative visual defects with surgical positioning and hemodynamic fluctuation. Measurement of blood urea nitrogen/ creatinine will determine the degree of chronic renal failure. An electrocardiogram [123] [124] and an echocardiogram[125] are required to detect myocardial ischemia, valve lesions, CHF, and ventricular outflow tract obstruction. Silent myocardial ischemia is likely due to lesions of the autonomic nervous system. A pharmacologic stress test may be required to determine if significant coronary artery disease is present, especially if the patient is sedentary. With an abnormal stress test or echocardiographic evidence of pulmonary hypertension, cardiac catheterization may be necessary. Careful neurologic examination is important to document peripheral lesions, [126] [127]especially if regional anesthesia is planned.

TABLE 10-16   -- Preoperative Preparation for Patients with Fabry's Disease



Quantify ocular involvement



Measure blood urea nitrogen/creatinine



Electrocardiogram and echocardiogram



Functional cardiac study



May need cardiac catheterization



MRI/CT if neurologic exam abnormal



Intraoperative Considerations ( Table 10-17 ).

Preoperative sedation should be considered to prevent excessive activation of the abnormal autonomic nervous system. Increased levels of monitoring may be required because of major organ system comorbidity. Abnormal temperature regulation should be assumed, and active warming and cooling devices should be present. Autonomic neuropathy is likely, and vasoactive drugs to treat sudden hypotension and hypertension should be prepared in advance.

TABLE 10-17   -- Anesthetic Management Issues with Fabry's Disease



Sedation to avoid sympathetic activations



Invasive monitoring



Temperature monitoring/control



Hemodynamic control



Airway management issues



Need for excellent analgesia



Centrally mediated chronic pain



Autonomic instability with neuraxial block



With general anesthesia, the airway should be evaluated in advance because of oropharyngeal lesions. Agent selection is determined by comorbidity. Excellent pain control should be planned, particularly in patients with chronic pain from peripheral nerve lesions. Pain control may require carbamazine or phenytoin.[128] If morphine has been successful in treating prior pain episodes, it may be useful postoperatively.[129] If chronic pain is treated with carbamizine,[130] increased metabolism of nondepolarizing muscle relaxants should be assumed and dosing of muscle relaxants should be guided by neuromuscular blockade monitoring. Regional anesthesia is a consideration; however, autonomic instability could exaggerate the hemodynamic instability normally associated with sympathectomy from central neuraxial blocks.[131] If CNS lesions are progressive, central neuraxial block is relatively contraindicated because of the possible presence of central demyelination.


Fabry's disease is a congenital defect of glycosphingolipid metabolism that results in massive deposition of the lipoproteins in visceral structures, causing organ dysfunction. Cardiovascular, pulmonary, neurologic, renal, and ocular dysfunction are common. Anesthetic preparation and care are determined by the presence and extent of major organ system disease.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


Herpes infections of the skin and mucous membranes are caused by infection with human herpes simplex virus (HSV-1 and HSV-2). Once systemic infection occurs, a primary outbreak is followed by a dormant state.[132] Recurring outbreaks result from activation. Oral and genital sites for primary infection are the most common. During the dormant state, the virus remains in the cells of the neuraxial ganglia. During the primary outbreak, the lesions are contagious by contact. After transfer to other surfaces, the viruses are only briefly contagious. Genital herpes in an active outbreak can be transferred to the neonate during transit through the birth canal. Not only is skin involved for the neonate, but devastating infection of visceral organs is a risk. Whereas genital herpes is almost always directly related to sexual contact, facial-oral infection has many causes and involves the majority of adults worldwide.[133] Reactivation is triggered by stress, fever, contact sports,[134] or surgical manipulation. The viruses move down the nerve by axonal flow and produce lesions. Numerous common lesions are listed in Table 10-18 .

TABLE 10-18   -- Manifestations of Herpes



Primary gingivostomatitis



Primary genital herpes



Recurrent facial-oral herpes



Herpesvirus cervicitis



Recurrent genital herpes



Herpes associated with HIV



Herpes in immunocompromised patients



Herpetic whitlow



Generalized herpes



Herpetic keratoconjunctivitis



Herpes encephalitis




Small, raised, confluent lesions are suggestive of the presence of the disease. The facial lesions are often confused with many other skin lesions, such as erythema multiforme, impetigo, and vaccinia. Genital herpes can be confused with fungal infections, urinary tract infection, syphilis, lymphogranuloma venereum, and genital papilloma. Mucopurulent herpes cervicitis is easily confused with infectious vaginitis. Recurrent infections are usually easily identified because of prior experience.[135]

Preoperative Considerations ( Table 10-19 ).

During primary outbreak, generalized viremia is present. Elective surgical procedures are unwise, because body fluids are contagious. Patients with herpetic whitlow can present for surgical drainage of infected finger tissue.[136] Topical and oral antiviral drugs are both therapeutic in acute episodes and part of suppression therapy to prevent outbreaks. Parenteral antiviral drugs can be lifesaving in generalized herpes and herpes encephalitis. [137] [138] [139] Detection of systemic infection is a priority. During viremia, transmission from primary lesions or systemic viremia is possible by instrumentation. This would make elective airway management during acute oral outbreak or neuraxial block during primary genital herpes unwise.

TABLE 10-19   -- Perioperative Issues in Patients with Herpes Infection



Generalized viremia during primary outbreak



Viral transfer with airway management



Central nervous system infection with neuraxial instrumentation



Protection of anesthetic equipment



Universal precautions



Intraoperative Care.

When emergency surgery is required during acute herpetic outbreaks, all body fluids from the patient should be considered contaminated. The anesthesia machine should be protected with filters and equipment cleaned as if contaminated. Nurses and equipment aides should be warned of the risk of transmission. Simple contact cleaning is effective, and contaminated surfaces remain contagious for only a brief interval.

No particular anesthetic agents or techniques offer any advantage. Central neuraxial block during acute or systemic episodes should be avoided. Other than avoiding viral transmission to other people, recurrent lesions have no specific issues.


Acute herpetic infections are associated with systemic viremia. Elective surgery and anesthesia should be avoided to prevent dissemination of the viruses. In particular, dural puncture could induce herpes meningitis and/or encephalitis. When emergency surgery is required, the lesions should be considered contagious. Anesthesia machine protection, appropriate cleaning, and warning health care providers of risk for exposure are essential. No particular anesthetic agents are indicated or contraindicated.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


Mastocytosis is caused by mast cell hyperplasia in the liver, spleen, bone marrow, lymph nodes, skin, and gastrointestinal tract.[140] Mast cells easily degranulate and symptoms related to release of mediators are common, including urticaria, flushing, abdominal pain, bone pain, diarrhea, nausea, and vomiting. This familial syndrome is based on abnormal expression of the gene that regulates mast cell production. There are a variety of manifestations of mastocytosis, and a classification system is presented in Table 10-20 .

TABLE 10-20   -- Manifestations of Mastocytosis


















Bone marrow aggregate









Lymph gland















Mastocytic leukemia



The clinical features for any given patient are determined by which mast cell mediators are produced in excess. Most patients have cutaneous lesions referred to as urticaria pigmentosa, which are small, reddish-brown, itchy lesions of the trunk and limbs. In aggressive forms, these lesions can become confluent and involve nasal and oral mucosa. Local heparin release creates a lesion with easy bruising by trivial contact. The noncutaneous manifestations of mastocytosis are related to mast cell infiltration of various organ systems. Gastritis and peptic ulcer disease result from hypersecretion secondary to increased plasma histamine levels. Abdominal pain, diarrhea, and malabsorption[141] are other manifestations directly related to mast cell invasion of gastrointestinal mucosa.[142] Liver and spleen involvement occur in some cases. The most common liver manifestation is elevation of liver enzymes, but severe cases can present as ascites and portal hypertension[143] associated with liver fibrosis.[144]Marked enlargement of the spleen occurs in a majority of cases. Bone lesions are caused by focal deposits of mast cells. Bone pain is the most common result, but pathologic fracture can occur.[145]Numerous hematologic abnormalities are associated with mastocytosis.[146] Systemic response to mediators is as varied as are the mediators chemically ( Table 10-21 ).

TABLE 10-21   -- Mast Cell Mediators




Pruritus, bronchoconstriction, gastric hypersecretion


Local anticoagulation, osteoporosis


Bone lesions


Vasopermeability, bronchoconstriction, vasoconstriction

Prostaglandin D2

Vasodilation, bronchoconstriction

Platelet-activating factor

Vasopermeability, vasodilation, bronchoconstriction


Cellular activation



Systemic mediator release can cause neuropsychiatric abnormalities, including irritability, decreased attention span, memory impairment, and secondary depression. [147] [148] There is an association between mastocytosis and eosinophilic granuloma.[149]


Most cases of mastocytosis are diagnosed by the characteristic skin lesions. Biopsy confirms the role of mast cells in various lesions (skin, mucous membranes, bone). Urine studies may reveal increased levels of metabolites of mast cell mediators. Without the presence of skin lesions, CT, bone scan, or endoscopy may be diagnostic. Because the systemic effects mimic other diseases with vasoactive release, workup should rule out carcinoid and pheochromocytoma by measuring urine 5-hydroxyindoleacetic acid and metanephrines.

Preoperative Considerations ( Table 10-22 ).

Gastric hypersecretion should be suspected in all mastocytosis patients. Gastric acid blockade and increased gastric emptying with metoclopramide should be considered. If liver disease is suspected, assessment of synthetic and coagulation function is required.[150] Anxiolysis may decrease mast cell activation. If chronic corticosteroids are used for treatment, stress-dose corticosteroids should be ordered for the perioperative period.

TABLE 10-22   -- Perioperative Issues with Mastocytosis



Gastric acid blockade



Delayed gastric emptying



Liver function testing



Coagulation testing



Stress-dose corticosteroids



Temperature support



Hemodynamic instability from histamine release



Invasive monitoring



Avoidance of histamine-releasing anesthetic agents



Histamine release with blood transfusion



Intraoperative Consideration.

Vasodilation makes hypothermia more likely, and active temperature support should be planned.[151] Release of mediators is increased by manipulation of lesions, which should be kept to the absolute minimum.[152] Bone pain indicates a risk of fracture, which should be considered during positioning. Hemodynamic instability may occur from mast cell mediator release.[153] Sudden, profound, intraoperative hypotension has been reported,[154] and epinephrine may be the intervention of choice.[155] As a result, invasive monitoring and immediate availability of vasoactive drugs is often required. Histamine release with transfusion can be massive; pretreatment with diphenhydramine should be routine.

Regional anesthesia is acceptable, but vasodilation may accentuate the consequences of neuraxial sympathetic block. Specific agents for general anesthesia should be selected to avoid further histamine release.[156] Light anesthesia may trigger histamine release.


Mastocytosis presents numerous anesthetic implications related to release of mast cell mediators. Cutaneous, gastrointestinal, and systemic issues are most prominent. Many of the mediators have potent vasoactive properties that can alter the course of any anesthetic procedure.

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Mucopolysaccharidoses occur because of genetic defects in enzymes that degrade intracellular complex molecules. The action of the abnormal enzymes leads to accumulation of these partially degraded compounds and secondary cellular and organ system pathology.[157] The specific enzyme defect determines the different syndromes ( Table 10-23 ). Accumulation of mucopolysaccharides (heparin sulfate, dermatan sulfate, and/or keratin sulfate) is the direct cause of the systemic manifestations. Accumulation occurs in CNS, peripheral nerves, ganglia, cardiac valves, coronary arteries,[158] liver, spleen, lymph nodes, retina, pituitary, and testicles. Skeletal and bony defects result from abnormal osteocytes and chondrocytes, which are enlarged and have multiple large vacuoles. In the area of the growth plates the chondrocytes are disorganized, leading to decreased growth and early closure.

TABLE 10-23   -- Mucopolysaccharidoses



Skeletal Defect


Sulfoiduron Sulfatase




Face, spine


N-acetyl-galactose-6 sulfate sulfatose

Face, spine, femur



Hands, face


Heparan sulfatase

Chest, clavicle



Differential Diagnosis and Clinical Manifestations.

Although similar, each syndrome has unique features. Hurler's syndrome results from accumulation of dermatan, and lesser amounts of heparin.[159] The head is enlarged with abnormal faces and poor dentition. Upper airway defects are common and severe sleep apnea may be associated.[160] Airway obstruction can be progressive and symptomatic.[160] Hypoplasia of the odontoid can occur, often presenting as quadriparesis requiring fusion.[161] Short neck, flaring of the thorax and kyphoscoliosis characterize the trunk. Flexion contractures are common. Chronic dislocation and dysplasia of the hip can be present.

Cardiac defects occur because of infiltration of cardiac cells,[162] and progressive accumulation around the valves, especially the mitral valve can be observed.[163] Retardation is common, and MRI reveals multiple small cystic lesions of white matter. Acute hydrocephalus has been reported with deposition of mucopolysaccharides in the lower brain.[164] Glaucoma from mucopolysaccharide deposition has been reported.[165]

Hunter's syndrome results from accumulation of heparan sulfate. Skeletal defects include absent thoracolumbar kyphosis, pediatric carpal tunnel syndrome, [166] [167] [168] abnormal facies, structural upper airway obstruction, and mild to moderate distortion of the chest. Progressive mucopolysaccharide deposition in the upper airway leads to airway obstruction and can present as stridor and airway compromise.[169] Sleep apnea is common.[160] In one case, difficulty with endotracheal intubation during airway surgery was related to bulging false cords and glottic stenosis from deposition of mucopolysaccharides ( Table 10-24 ).[170]

TABLE 10-24   -- Comorbidities Associated with Mucopolysaccharidoses



Progressive airway obstruction



Obstructive sleep apnea



Cervical spine instability






Chronic dislocation of hip



Cardiac conduction defects






Chronic hydrocephalus






Morquio's syndrome results from accumulation of keratan sulfate and chondroitin-6-sulfate. These children are normal at birth but demonstrate spine dysplasia within 12 to 18 months. Severe thoracolumbar kyphoscoliosis occurs early in life.[171] Abnormality at the craniocervical junction is almost universal with hypoplastic odontoid,[171] atlantoaxial instability, [172] [173] and, in some, severe cervical cord compression [174] [175] or quadriparesis.[176] Spinal cord compression and myelopathy is a common chronic disability.[177] Dwarfism results from limited development of the trunk. Joint laxity, abnormal faces, and valgus/varus deformity of the knees are common. The CNS is usually not involved; mental retardation is uncommon. Life expectancy is shortened by progressive kyphoscoliosis. Fusion of C2 to the occiput is frequently required.[178]

Preoperative Preparation ( Table 10-25 ).

Obstructive sleep apnea can be associated with pulmonary hypertension and right ventricular dysfunction. Respiratory mechanics can be compromised from airway obstruction, pectus deformities, or mechanical distortion of the thorax[179] and deposition in the tracheobronchial tree.[180] If suspected, transthoracic echocardiogram with attention to the right ventricle and right-sided valves is indicated. If a murmur is detected, echocardiography is also indicated because of the potential involvement of the aortic and mitral valves from mucopolysaccharide deposition [163] [181] and the resultant cardiomyopathy.[182] Even in young children, an electrocardiogram is important because of cardiac defects from accumulation of mucopolysaccharides and early-onset coronary artery disease. [158] [183]Radiographic evidence of severe thoracic deformity suggests increased risk of postoperative ventilatory insufficiency. Radiographic investigation of the cervical spine may be required if limited range of motion or abnormal surface anatomy is observed. Because odontoid development may be abnormal, atlantoaxial instability may be present. Flexion-extension cervical spine films are indicated, and if cooperation is impossible, instability must be presumed. With Hurler's syndrome, C2-occiput fusion may be required for atlantoaxial instability owing to odontoid hypoplasia or the onset of spontaneous quadriplegia.[184]

TABLE 10-25   -- Preoperative Issues in Patients with Mucopolysaccharidoses



Pulmonary function testing









Chest radiograph



Cervical spine radiographs in flexion and extension



C-spine fusion



Intraoperative Management.

A large tongue, thickening of airway structures, and friable tissue make airway management more difficult. Plans for difficult airway management should be made for any patient with one of these syndromes.[185] Bronchospasm may be more common.[186] In one series, airway issues occurred in 53% of patients.[187] Death from inability to ventilate or intubate has been reported in patients with Hurler's syndrome. [188] [189] Emergency tracheostomy was lifesaving in others. [183] [190] Use of the LMA has been helpful in some of these children with difficult airway management, to control the airway and to assist with fiberoptic intubation.[191] LMA use has also been a failure.[192] Airway management can be challenging when cervical cord compression is symptomatic and the patient is uncooperative.[174] Transoral decompression of the brainstem and proximal cervical spine may be the chosen surgical procedure.[177] With Hurler's syndrome, progressive airway obstruction may require tracheostomy if laser decompression is not possible.[169]

Contractures may make positioning very difficult, and pressure injuries should be actively prevented. Because of tissue deposits, contractures, and bony defects, intravenous access may be very difficult. Deformities of the skeleton make regional anesthesia difficult and potentially dangerous. Even with successful catheterization of the epidural space, epidural anesthesia can be incomplete secondary to deposition of mucopolysaccharides in the epidural space.[193] Continuous spinal anesthesia has been used successfully in a child with Morquio's syndrome[194] and a child with Hurler's syndrome[195] in whom intubation could not be accomplished. During general anesthesia, recognition of acute cord compression would be difficult, and, if unrecognized, devastating neurologic injury could be the outcome[196] Massive intraoperative stroke has also been reported in a child.[197] There are no specific issues with anesthetic agents unless comorbidity is present, such as cardiac dysfunction. Complete heart block during anesthetic management has been reported.[198] Delayed awakening has been associated with Hunter's syndrome in one case.[199] Progressive respiratory failure leading to death has been reported after surgery, related to the mechanical limits of respiratory mechanics.[200] Increased sensitivity to opioids should be assumed; and because of the high probability of abnormal upper airway, airway obstruction will be even more likely during acute pain management ( Table 10-26 ).

TABLE 10-26   -- Anesthetic Issues with Mucopolysaccharidoses



Difficult airway management



Difficulty with ventilation



Acute airway obstruction



Difficult positioning/injuries



Incomplete epidural block



Complete heart block



Delayed emergence



Challenging acute pain control due to obstructive sleep apnea




Patients with congenital defects in mucopolysaccharide metabolism present with anesthetic issues mainly because of skeletal structural issues. Airway management, positioning, and intravenous access problems are likely. Asymptomatic compression of the spinal cord can be present, and spinal cord lesions from positioning during general anesthesia have been reported. Abnormality of the thorax creates diminished respiratory function and increases the probability of postoperative respiratory failure.

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Neurofibromatosis is a syndrome caused by the abnormal deposition of neural tissue within the nervous system, endocrine system, visceral structures, and skin.[201] The origin is congenital, with an autosomal dominant mode of transmission. Two variants are known[202]: central neurofibromatosis (10%) and von Recklinghausen's neurofibromatosis (85%). [203] [204] Both have characteristic skin lesions. The central variant is associated with multiple slow-growing CNS lesions, including bilateral acoustic neuroma in most cases.[205] With the von Recklinghausen variant, osseous lesions, renal artery involvement, optic nerve compression,[206] and hydrocephalus can occur.[207] Involvement of the mid brain can cause a variety of endocrine disorders. Spinal cord lesions can create paraplegia.[208]

Clinical Manifestations ( Table 10-27 ).

Deposition of proliferating neural tissue causes organ-specific dysfunction. Proliferation in osseous tissue causes cyst formation, osteoporosis, and fracture. Long-bone fracture, osteoarthritis of weight-bearing joints, and kyphoscoliosis are potential pathophysiologic consequences. Deposition of neural tissue in the oropharynx and larynx can cause dysphagia or airway incompetence. [209] [210] Interstitial lung disease can result from deposition of neural tissue.[211] Other respiratory involvement can result from chronic hypoxemia, causing pulmonary hypertension, right-sided heart strain, and respiratory failure from cor pulmonale. Obstruction of the urinary tract and/or renal artery involvement can cause renal failure. Pelvic obstruction can complicate obstetric care. [212] [213] Neuroendocrine proliferation can lead to pheochromocytoma and other less common endocrinopathies.

TABLE 10-27   -- Clinical Manifestations of Neurofibromatosis



Bone cyst, osteoporosis, fracture






Airway incompetence



Interstitial lung disease






Retinal artery lesions



Optic nerve compress



Spinal cord compromise



Renal failure



Neuroendocrine disorders



Pelvic outlet obstruction: difficult obstetric care




The diagnosis of neurofibromatosis can be delayed by the manifestations in a major organ system. The most common diagnostic evidence comes from observation of the classic skin lesions called café-au-lait spots. [214] [215] The café-au-lait spots can be confused with pigmented nevus. Skin biopsy is definitive.

Preoperative Considerations ( Table 10-28 ).

The multiple sites of involvement of advanced neurofibromatosis determine the priorities for presurgical preparation. The primary site of involvement is the nervous system, which must be investigated completely. CT or MRI of the head[216] will identify masses, midline shift, or increased intracranial pressure and will demonstrate any potential risk of herniation. Occult spinal cord tumors have been reported.[217] If spinal cord involvement is suggested by weakness, pain, or other long tract signs, radiographic investigation is required. Meningocele and bony anomalies have been reported. [218] [219] In particular, quantification of risk for airway management may require MRI examination of the cervical spinal cord.[220] Discovery of spinal osseous lesions would further protect the patient from spinal cord injury from fracture. The probability of pulmonary involvement can be suggested by history. If the history or physical examination (kyphoscoliosis) is positive,[221] spirometry and arterial blood gas analysis may be necessary. If there are signs of cor pulmonale, echocardiogram and even angiography may be required. If the upper airway is involved, indirect laryngoscopy should be performed by an experienced endoscopist.

TABLE 10-28   -- Perioperative Issues for Patients with Neurofibromatosis



CT/MRI of head



Cervical spine radiographs in flexion/extension



Pulmonary function tests






Blood urea nitogen/creatinine measurement



Detection of abnormal electrolytes



Difficult airway management



Respiratory compromise with high neuraxial block



Temperature control



Abnormal response to muscle relaxants



Other issues that should be considered include renal failure, endocrine hyperplasia (pheochromocytoma), and optic nerve involvement. If regional anesthesia is a consideration, the site for the block must be free of lesions and anatomically normal enough to perform the block. Abnormal pituitary function is possible and occult electrolyte abnormalities should be investigated.

Intraoperative Considerations.

When the airway or cervical spine is compromised, careful awake fiberoptic intubation is required. The degree of invasive monitoring is determined by the extent of major organ system compromise. When advanced pulmonary compromise is present, the possibility of prolonged postoperative mechanical ventilation must be considered.[222] In this subset of patients, central neuraxial block should be undertaken with the understanding that high levels of truncal somatic block could precipitate respiratory failure. Epidural analgesia for labor has been reported with success.[223] With advanced kyphoscoliosis, access for neuraxial block may be difficult or impossible. Even with successful epidural catheterization, the block can be incomplete because the epidural space may be partially obliterated. Abnormal temperature regulation should be assumed and active heating provided. No unique drug indications or contraindications are present, although abnormal response to muscle relaxants has been reported. [224] [225] [226]


Neurofibromatosis is a syndrome with consequences related to deposition and proliferation of abnormal neural tissue. Consequences are manifest in the central autonomic and peripheral nervous system, spine and long bones, airway, kidneys, and eyes. Anesthetic management is modified by CNS pathology, respiratory compromise, difficult airway management, endocrine and electrolyte abnormalities, and abnormal skin surface.

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The majority of patients with osteogenesis imperfecta (OI) have a genetic defect in the genes that creates structural collagen.[227] The subclassification of collagen found in the skeletal system, including ligament, tendon, and bone, is type I collagen. In OI there is either a quantitative defect or a structural deficiency of type I collagen.[228] Of the four or more genetic variants there is a range between extreme bone fragility that leads to death during or shortly after delivery to skeletal changes subtle enough to be confused with child abuse. The consequence of defective structural collagen is disturbance in the formation of enchondral and intramembranous bone. Ligament and tendon structure is variably defective and/or incomplete. The bone trabeculae most responsible for tensile strength are thin, and the interlinkage is diminished.

Clinical Manifestations. ( Table 10-29 ).

In the most extreme cases, multiple fractures occur during delivery. These cases are usually associated with neonatal demise. In the nonlethal forms of the disease, the most significant feature is brittle bone structure. Fractures occur from minimal force. More fractures occur in the lower extremities, perhaps because they are exposed to more trauma. The femur is fractured more often than the tibia for the same reason. Deformity of the pelvis can be extreme, and bowel obstruction from protrusion fracture of the acetabulum has been reported.[229] Spinal deformity develops because of decreased ligamentous stability, compression fractures, osteoporosis, and spondylolisthesis.[230] Kyphoscoliosis is the most common lesion, but others, including cervical spine instability/fracture[231] and upward migration of the odontoid, causing brain stem compression and altered cerebrospinal fluid flow, have been reported. [232] [233] The teeth are malformed and fracture easily.[234] Blue sclera, thin sclera and cornea, and exophthalmos are common ocular abnormalities, and there has been a report of central retinal artery occlusion in the prone position in an OI patient.[235] An association with malignant hyperthermia has been reported, [236] [237] [238] although muscle biopsy from a clinical case did not test positive for malignant hyperthermia susceptibility.[239] Platelet dysfunction has been associated with OI.[240]Associated cardiac anomalies include patent ductus arteriosus, atrial septal defects, ventricular septal defects, and valvular defects.[241] Acquired cardiac defects associated with OI include aortic regurgitation,[242] mitral regurgitation from chordal rupture, [243] [244] and cystic degeneration of the proximal aorta.[245]

TABLE 10-29   -- Clinical Manifestations of Osteogenesis Imperfecta



Multiple fractures with delivery



Fracture with minimal stress



Spinal deformity



Compression fractures






Abnormal dentition



Ocular lesions



Patient ductus arteriosus



Atrial septal defect



Valvular lesions




In infancy, OI can be confused with achondroplasia or other forms of dwarfism because of skeletal or skull anomalies with a common appearance. In childhood, idiopathic juvenile osteoporosis will also present in a similar manner. A confounding variable is child abuse, where fracture is also a feature of diagnosis. [246] [247] [248] [249] [250] In less severe forms of osteogenesis imperfecta, investigation of possible child abuse can be a cause for serious delay in diagnosis.

Preoperative Preparation ( Table 10-30 ).

The anatomic defects of osteogenesis imperfecta determine the preanesthetic preparation. Because of the nature of OI, most indications for surgery will be urgent, that is, treatment of fractures. This does not eliminate the issues of preparation. Creatine phosphokinase (CPK) levels should be measured because they can be elevated if there is risk of malignant hyperthermia. Because platelet function may be abnormal,[251] complete measurement of coagulation is indicated if there are any signs of coagulopathy, such as excessive bleeding, easy bruising, or blood with oral hygiene or bowel or bladder function.[252] Unexpected massive bleeding without an obvious surgical etiology has been reported in a patient with OI.[253] Because cor pulmonale can result from thoracic deformity, and because of associated congenital heart disease, a preoperative echocardiogram is required if a normal study is not previously known. Severe kyphosis will predict mechanical dysfunction of the lungs and should be evaluated preoperatively with spirometry.[254] Multiple issues with the skull and spinal column must be investigated radiographically, including brain stem compression, atlantoaxial instability, and cervical spinal cord compression. Hypoplasia or fracture of the odontoid is a significant risk[255] and must influence approaches to airway management. Basilar impression may occur, requiring decompression of the foramen magnum. [232] [256] [257] [258] [259] If undetected, normal range of motion with basilar impression [233] [260] or soft odontoid[260] could cause neurologic catastrophe.[261] Minor trauma has been reported to be associated with death from brain stem compression by this same mechanism.[232] Congenital or progressive kyphoscoliosis can interfere with pulmonary function, and spirometry and arterial blood gas analysis may be indicated for major surgery, especially procedures to stabilize progressive scoliosis. Reports of retinal artery anomalies associated with OI make assessment of preoperative visual activity valuable.

TABLE 10-30   -- Perioperative Issues with Osteogenesis Imperfecta



Creatine phosphokinase measurement: high levels suggest risk of malignant hyperthermia



Evaluation of coagulation



Electrocardiogram, echocardiogram



Central nervous system and cervical spine evaluation



Pulmonary function testing



Visual acuity



Positioning issues



Airway management issues



Bony injury during neuraxial block



Risk of malignant hyperthermia



Fracture risk with stormy emergence



Intraoperative Management.

Positioning must be performed with extra care because long-bone fractures can result from minor trauma. Fragility of connective tissues makes padding important, to avoid ligament or tendon disruption. Achilles and patellar tendons are particularly at risk. Any bone is susceptible to fracture, and potential serious consequences can occur. A fatal intraoperative hemorrhage resulted from occult fracture of a rib during instrumented spine fusion, resulting in massive transfusion and coagulopathy.[262] A fracture of the femur from minor trauma caused a compartment syndrome.[263] Airway management must be gentle because fractures of the mandible, maxillary surface, and cervical spine are all possible if excessive force is applied.[264] Awake fiberoptic intubation may be the best option, although successful use of an intubating LMA has been reported.[265] Regional anesthesia is possible, but needle placement near bony structures may be problematic. Puncture of bone could cause fracture in the postoperative period. Intraosseous injection is also possible, is difficult to recognize, and could be associated with local anesthetic toxicity. However, successful use of an epidural catheter for anesthesia and postoperative analgesia for cesarean section has been reported. [267] [268] Intramuscular ketamine has been used in the past as a sole anesthetic for fracture reduction, [241] [269] although adequate muscle relaxation was problematic in some instances. Because there is risk of malignant hyperthermia, a nontriggering anesthetic should be planned for general anesthesia, and total intravenous anesthesia (TIVA) may be an excellent option.[269] Succinylcholine should be avoided. Metabolic acidosis without other signs of malignant hyperthermia has also been reported. [233] [271] [272] The risk of hyperthermia[240] requires that there be access to active cooling. Smooth emergence should be the goal, because coughing, bucking, or excitement could cause multiple fractures. When the surgical procedure is spine fusion, this is particularly important because the fusion instrumentation can be disrupted and threaten the integrity of the spinal cord.[272] Extensive cervico-occipital decompression with fusion would almost certainly require prolonged intubation and sedation before extubation.[232] Any positioning other than supine must take into account the risk of retinal artery occlusion, and external pressure on the eyes should be carefully avoided.


Anesthesia for patients with osteogenesis imperfecta is unfortunately a common experience because of the frequency of long-bone fracture, requiring fixation. Anesthetic issues arise from abnormalities of bone, including cervical spine instability, brain stem herniation, and kyphoscoliosis. Positioning must be careful, because fracture from minimal stress can occur. Similar care with airway management is necessary to avoid fracture of the mandible, maxilla, or cervical spine. Susceptibility to malignant hyperthermia must be an element of any plan for general anesthesia. Regional anesthesia should be performed with care if close to cortical bone to avoid fracture or unrecognized intraosseous injection.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


Osteoporosis is a generalized atrophy of bone that results in decreased bone mass without change in the nonmineralized elements. There is no alteration in the structural appearance of osteoporotic bone, although the tensile strength is reduced as bone density decreases. Disproportionate loss of trabecular bone is a distinguishing feature of osteoporosis.[273] When the trabecular (structural) bone volume reaches 10% or below, osteoporosis is confirmed and the risk of stress fracture becomes significant. The most common association is loss of estrogen in postmenopausal women[274] or as a product of either aging or disuse. Exercise may prevent disuse osteoporosis. [276] [277] Osteoporosis has also been reported as associated with rheumatoid arthritis and osteoarthritis.[277] Reduced intestinal absorption of calcium can create osteoporosis with normal aging, in association with primary biliary cirrhosis [279] [280] or chronic cholestatic liver disease.[280] Bone remodeling favors absorption more and more as a function of age. Although the tensile strength of all bone is reduced, some bones are more at risk for fracture. These include the thoracic and lumbar spine, the proximal femur, the proximal humerus, and the wrist. Compression fractures of the thoracic and lumbar spine are also common.[281] Midforearm fractures result from minimal trauma if Colles‚ fracture of the wrist does not occur.[274] When bone density is reduced more than 50%, spontaneous fractures of vertebral bodies may occur in response to minor compression loading, such as coughing or sneezing. Acute pain and muscle spasm are the presenting symptoms and can be the indication for surgical procedures to stabilize the spine (percutaneous vertebroplasty). There is a clear genetic predisposition to osteoporosis, with women of Northern European descent being at highest risk.

Osteomalacia is a generalized softening of bone resulting in reduced tensile strength of bone. It results from a wide variety of causes, having in common deficient vitamin D. This can be extrinsic, as in nutritional deficiency, [283] [284] or intrinsic related to malabsorption. [285] [286] The result is defective or incomplete mineralization of bone. In contrast to osteoporosis, osteomalacia can occur at any age, including childhood. Bone tenderness, back pain, and abnormal gait are the most common clinical symptoms. Long-bone fractures are more likely and occur with less trauma.[286] Rarely, this can occur with symptoms of hypocalcemia when inadequate skeletal calcium is available for acute mobilization. Severe deformities of the spine (kyphoscoliosis) or pelvis (acetabular protrusio) can be the initial presentation and the indication for surgery. Radiating sciatic pain can also be both diagnostic and an indication for surgery. Skeletal muscle can have abnormal function in advanced osteomalacia, and muscle weakness can be significant. Respiratory muscle groups are not spared, and respiratory muscle failure can be accelerated. Using conservative definitions, up to 4% of geriatric hospital patients have the clinical criteria for osteomalacia. Chronic corticosteroid use can cause osteopenia, [288] [289] especially associated with rheumatoid arthritis. [290] [291] Comorbidities can cause osteomalacia. Hepatic osteodystrophy can occur in end-stage liver disease,[291] either based on malnutrition (alcoholism) or steatorrhea and malabsorption of vitamin D. Chronic ingestion of alcohol can impair calcium uptake by the intestine, [293] [294] and osteomalacia can be the result.[294] In cholestasis, impaired absorption of vitamin D and impaired metabolism can be expected. Long-term anticonvulsant therapy can result in osteomalacia from malabsorption of calcium. [289] [296] End-stage renal disease or nephrotic syndrome[296] can cause renal osteodystrophy from malabsorption of calcium and failure of mineralization of bone, secondary to abnormal vitamin D metabolism.[297] Softened bone may result in fractures proximate to large blood vessels.[298] Osteomalacia is associated with metastatic prostatic cancer. [300] [301] [302]

Osteopetrosis (marble bone disease) is a rare disorder associated with increased bone density (osteosclerosis), associated with clinical issues related to skeletal abnormality.[302] The range of severity is wide, from children with genetically based generalized skeletal defects[303] to asymptomatic adults, identified because of easy fracture and workup for metabolic bone disease.[304] Radiographic manifestations include sclerosis of bone, abnormal growth, and symmetrically increased bone mass, most obvious near the end of the long bones and pelvis. In some cases, alternating density and lucent areas can be visible radiographically, suggesting risk for pathologic or traumatic fracture.[305] Cranial nerve compression can be associated with blindness, deafness, and facial nerve paralysis.[302] Rare presentations include diffuse idiopathic skeletal hyperostosis (DISH),[306] which manifests with increased bone mass and density at ligament and tendon insertions of the spine.[307] Ankylosis can create deformity and decreased mobility. Hypertrophic osteoarthropathy is an osteopetrosis variant that occurs secondary to other disease processes, including chronic obstructive pulmonary disease, lung cancer,[308] bronchiectasis, pulmonary fibrosis, congenital heart disease, liver cirrhosis, cystic fibrosis,[309] chronic gastrointestinal disease, renal tubular acidosis,[310] cystic fibrosis, multiple myeloma,[311] and other chronic diseases. Long-bone abnormality is more likely altered compared with the trunk and vertebral column, although spondylolysis has been reported.[312] Intracranial calcification has been reported in children with osteopetrosis, associated with carbonic anhydrase II deficiency.[313] Although fracture is less common, nonunion of fracture in children is more likely.[314] Hyperostosis associated with excessive ingestion of vitamin D has been reported. [316] [317]

Differential Diagnosis.

The differential diagnosis of these diseases is based on radiographic examination and bone density studies. The patient with repeated fractures or a postmenopausal female with bone pain may undergo a skeletal radiographic survey. The abnormalities can include decreased bone density (osteoporosis), decreased mineralization (osteomalacia), or excessive mineralization (osteopetrosis). All have in common structural weakness of bone and increased risk of fracture.

Preoperative Preparation ( Table 10-31 ).

In patients with structural defects of bone, anatomic deformity of the airway and thorax is possible. The airway can be abnormal secondary to decreased range of motion of the neck. Despite diminished mobility, instability is also possible, secondary to fragility of the structural elements, such as the odontoid. Even if mobility is normal, decreased tensile strength may be present. Structural abnormality of the thorax may diminish pulmonary reserves. If kyphosis, scoliosis, and/or rib cage deformity is present, chest radiography and spirometry may be indicated. Because bone pain may be an indicator of structural deficiency, an inventory of bone pain sites may be a guide to positioning issues in the operating room.

TABLE 10-31   -- Perioperative Issues with Structural Defects of Bone



Airway issues



Fragile cervical spine



Diminished pulmonary reserves



Stress-dose corticosteroids



Assessment of causative organ-system



Positioning issues



Risk with routine airway maneuvers



Cervical spine ankylosis



Increased risk of bleeding



Injury to bone with regional anesthesia



If osteoporosis is secondary to chronic corticosteroid use, stress-dose corticosteroids are indicated. Osteomalacia is often a secondary condition; and when caused by end organ failure, investigation may be required. If secondary to severe liver disease, the synthetic functions of the liver should be measured, including proteins and coagulation testing (prothrombin time, activated partial thromboplastin time). If related to chronic renal disease, blood urea nitrogen and creatinine measurements are needed to guide anesthetic care. Osteopetrosis can also be a secondary condition, and primary causes in the lungs and heart would need to be investigated and evaluated to guide anesthetic care.

Intraoperative Management.

Positioning should be careful to avoid fracture. The skin is also fragile in some patients.[317] The management of the airway could be either difficult or dangerous with advanced osteoporosis. Awake fiberoptic intubation may be necessary. Positioning of the patient can be difficult, and the risk of fracture with minimal stress must be considered in all these conditions. Instrumentation of osteopetrotic bone can be difficult due to density[318] and associated with increased levels of bleeding and prolonged surgical times. [303] [320] There is no interaction between anesthetic agents and structural bone disorders, unless they are secondary to other diseases (e.g., end-stage liver disease, chronic renal failure) that have independent interaction issues. Regional anesthesia can be used, but the potential for trauma to abnormal bone must be considered. Chronic compression fractures of the lumbar and thoracic spine may make access to neuraxial block sites technically difficult or impossible. Besides injury to bone, the possibility of intraosseous injection with rapid plasma uptake of local anesthetic must be considered. In patients with osteopetrosis, ankylosis of the dorsal spinal column may be present, [321] [322] making neuraxial block difficult or impossible. There are no unique recovery issues.


Osteoporosis, osteomalacia, and osteopetrosis are disorders associated with reduction in the tensile strength of bone, which create indications for surgery and present anesthetic issues. These issues are focused on the skeletal anomalies that result and the comorbidities that are the primary causes of the disorders. Anesthetic care is modified by airway issues, risk of positioning injuries, and potential technical issues with regional anesthesia.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


Paget's disease of the bone is a process of unknown etiology that causes excessive resorption and subsequent abnormal remodeling that results in abnormally thickened bone with paradoxically reduced tensile strength. It may be related to excess parathyroid hormone or decreased calcitonin levels.[322] Paget's disease clearly has a genetic basis and is found most frequently in residents of Anglo-Saxon countries and their descendents. [324] [325] [326]

Paget's disease occurs in phases. The first phase involves active resorption of bone, and pain may occur.[326] Rapidly, new bone is deposited in an asymmetrical pattern. Pain will continue if it is present at the start of this phase, or it may occur as a new sign. The final phase is not usually associated with pain but is characterized by the proliferation of irregularly shaped trabeculae, which create a mosaic appearance in affected bone. In this final phase, the cellular content of bone is reduced, as is the tensile strength. Fracture through affected bone heals with a disorganized pattern. Collagen is prominent in the fracture callus for prolonged intervals. Vascular hypertrophy occurs during fracture repair and during the first two phases of the onset of Paget's disease. During instrumentation of this bone, bleeding will be significantly greater than normal. The abnormal remodeling of bone has been suggested as etiologic in familial cases of osteosarcoma that develop in pagetoid bone. [328] [329] [330]

Pain is the most common symptom that leads to the diagnosis of Paget's disease. Pain may be related to bone resorption, inflammation, or microfracture. Weight-bearing increases the pain in affected long bones. Pain may be caused by hyperemia after microfracture or stretching of periosteum. Weight bearing also leads to deformity, such as acetabular protrusion.[330] Osteoporosis of the skull, followed by exuberant deposition of bone and increased size and weight of the skull, can occur. Changes in the skull are commonly associated with hearing loss.[331] Excessive ossification of the foramen magnum can lead to neurologic symptoms from compression of the cerebellum in the posterior fossa or from cerebral tonsillar herniation.[332] Hydrocephalus or compression of the cervical spinal cord are possible. Hydrocephalus associated with dementia has also been reported from pathologic changes of the base of the skull related to Paget's disease. [334] [335] Anatomic abnormality of the temporal bones may result in abnormal balance and hearing loss and in optic neuropathy from bony compression.[335] Paget's disease can involve the mandible, maxilla, and teeth, further increasing the abnormal configuration of the head.[336] Dental extraction is commonly more difficult and associated with increased bleeding during and after the procedure.[337] Paget's disease of the upper cervical spine can cause spinal cord compression or atlantoaxial instability.[338] Proliferation of bone can result in compression of the spinal cord or nerve roots, most particularly in the lumbar and thoracic regions,[339] or spondylitis.[340]Lumbar spinal stenosis is a common manifestation of Paget's disease, requiring surgical intervention.[341] Coincident ankylosing spondylitis has been reported.[326] Knee and hip pain associated with sclerosis and deformity are common in advanced Paget's disease.

Fractures are the most common pathologic manifestation of Paget's disease after bone pain. The incidence of nonunion of these fractures is high. Microfracture through an area of active resorption of bone during early onset of Paget's disease may lead to spread of the lesions to surrounding bone. Rarely, malignancy (osteosarcoma) may occur in bone affected by Paget's disease. Renal calculi and gout are manifestations of abnormal calcium metabolism. Excessive blood flow to bone affected by Paget's disease can cause congestive heart failure. Calcification of cardiac structures (especially valves) is common. When calcification involves the cardiac structures, arrhythmia and heart block can result. There is a correlation between Paget's disease and calcific disease of the aortic valve. Peripheral vascular disease based on arterial calcification has been reported ( Table 10-32 ).

TABLE 10-32   -- Comorbidity Associated with Paget's Disease



Bone pain



Acetabular protrusion



Hypertrophy of skull



Compression at foramen magnum



Compression of cerebellum






Hearing loss, optic neuropathy



Abnormal mandible maxilla



Cervical spine instability



Lumbar spine stenosis



High incidence of fracture



Nonunion of fracture






Calcific cardiac conduction, valved disease



Peripheral vascular disease



Diagnosis and Treatment.

Paget's disease can be confused with a variety of bone disorders, including osteomalacia, osteoporosis, and osteopetrosis. The unique radiographic presentation of Paget's disease is usually the element that establishes the diagnosis.

Drug treatment is usually reserved for either symptomatic or advanced cases. Antimitotic drugs, such as colchicine, have been used for symptomatic relief, with the concomitant issues with bone marrow suppression.[342] Bone pain can be modified with either calcitonin[343] or biphosphonates.[344] High cardiac output can be treated with either option but may be more effective with biphosphonates.[345]The risk of osteomalacia,[346] stress,[347] and pathologic fractures[348] is higher with biphosphonates. [350] [351] [352] A limitation of calcitonin therapy is the development of resistance. Mithramycin has been used in the treatment of hypercalcemia secondary to Paget's disease.[352] It has also been used for severe bone pain refractory to other pharmacologic options. Administration is challenging since mitramycin must be administered intravenously and carefully because it is highly cytotoxic. Nausea and vomiting are commonly associated with its administration. Abnormal platelet function, hepatotoxicity, and nephrotoxicity are associated with mithramycin therapy and treatment with mithramycin should trigger evaluation of these systems.[353]

Preoperative Preparation ( Table 10-33 ).

Because of the abnormal bone metabolism, the potential for electrolyte abnormalities should be considered. If there is enlargement of the skull, CNS pathology is possible, including increased intracranial pressure and compression of the brain stem, cerebellum, and/or spinal cord. Although plain radiography of the skull will yield some information, especially if there is involvement of the maxilla or mandible, CT or MRI is needed to identify increased intracranial pressure, mass effect, or impending herniation at the foramen magnum. If there is bony abnormality of the spine, radiographic examination is required to look for spinal cord compression or anomalies that would risk injury to the spinal column during airway management. Flexion-extension films of the neck to look for atlantoaxial instability are indicated.

TABLE 10-33   -- Perioperative Issues with Paget's Disease



Abnormal electrolytes



Central nervous system at risk



Unstable cervical spine



Electrocardiogram, echocardiogram



Carotid ultrasound



Difficult airway management



Risk of injury with routine airway maneuvers



Excessive blood loss



Because of calcific changes in the cardiovascular system, comorbidities should be sought. Basic electrocardiography may reveal lesions in the conduction system. Calcific valvular disease would be detected by cardiac auscultation, and murmurs may require evaluation by echocardiography. Carotid bruit may trigger a carotid ultrasound. As described earlier, specific therapies for Paget's disease may necessitate detection of renal, hepatic, or platelet function abnormalities. If significant deformity of the thorax is noted, spirometry may be required to measure pulmonary reserves.

Intraoperative Issues.

Airway management can be difficult related to bone changes in Paget's disease. Both pain and deformity will make positioning difficult. Excessive force should be avoided, secondary to the risk of fracture through weakened bone. Regional anesthesia can be used, but radiographic examination may be required before central neuraxial block to avoid needle instrumentation through pathologic bone. If range of motion of the spine is severely restricted, review of spine radiographs may reveal ankylosis, which presents severe technical issues for central neuraxial block.[326] Excessive bleeding occurs routinely with bone affected by Paget's disease, and increased blood loss can be expected compared with comparable procedures on nonpagetoid bone.[354] Preparation for possible massive transfusion with lower extremity joint reconstruction is indicated.[355] Sclerotic bone is more difficult to instrument, which may prolong the surgical time and further increase blood loss. There are no specific interactions between Paget's disease and anesthetic agents, except where consequences of treatment cause organ damage or dysfunction.


The anesthetic management of Paget's disease is complicated by the structural consequence of the disease, including fracture deformity and CNS dysfunction. The symptoms of Paget's disease, including pain and weak bones, present issues in patient handling in the perioperative period. When Paget's disease is symptomatic, treatment may be necessary and some of the options have anesthetic implications.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


Panniculitis is a term for a group of diseases caused by inflammation of subcutaneous tissue. The eruption of clusters of edematous masses in the subcutaneous tissue occurs most often on the trunk and thighs but can involve the neck and face. The massive inflammatory response has systemic manifestations, including malaise, myalgia,[356] fatigue, and fever.[357] In rare cases, the fat of visceral organs can be involved. Inflammation of fat around the spleen, liver, adrenals, or myocardium can cause serious organ damage. Diffuse adenopathy is common. Bone marrow suppression can cause pancytopenia and bleeding events. Rare causes include chemical panniculitis, usually from subcutaneous infection, cold panniculitis,[358] where fat necrosis is triggered by exposure to cold, infection, [360] [361] [362] and factitial panniculitis from self-injection. In neonates, massive subcutaneous fat necrosis can occur, but fortunately this is short lived and reasonably well tolerated. [363] [364] Some forms of panniculitis are caused by serious systemic diseases, such as pancreatitis, lupus, [365] [366] sarcoidosis,[366] renal failure, leukemia,[367] and lymphoma. One variant of panniculitis is associated with vasculitis in the same parts of the body in which needle trauma has induced panniculitis.[368] The consequence of the vasculitis is increased severity of tissue injury and delayed healing. Erythema nodosum is a form of panniculitis. Articular lesions have been reported.[369]

Differential Diagnosis.

The lesions of panniculitis are initially confused with many other skin conditions. Lesions that are confined to subcutaneous tissue and fat are diagnostic. Although rare, panniculitis can be diagnosed during the workup of organ failure found to be associated with fat necrosis. There is an association between α-antitrypsin deficiency and panniculitis.

Preoperative Considerations ( Table 10-34 ).

The primary issue for presurgical preparation of patients with panniculitis focuses on care of the lesions and identification of any comorbidity caused by fat necrosis. Pressure on the lesion could cause extension. Ulcerated lesions should be protected from infection. Assessment of liver function and blood urea nitrogen/creatinine should be obtained to rule out organ dysfunction. An abnormal electrocardiogram and poor exercise tolerance could suggest cardiac involvement. When the lesions create the need for surgery (abscess, vascular compromise), evaluation should focus on functional status if fuller evaluation would delay urgent surgery. Treatment with corticosteroids mandates stress-dose corticosteroids in the perioperative period. When immunosuppressants or antimetabolites are used, organ toxicity should be investigated.

TABLE 10-34   -- Perioperative Issues in Patients with Panniculitis



Identify cause of fat necrosis



Positioning pressure causing lesions






Vascular compromise



Stress-dose corticosteroids



Inflammation of visceral organs



Intraoperative Considerations.

Positioning can be an issue when numerous lesions are present. Anesthetic technique is dictated by other organ system involvement and urgency of surgery. If there are clusters of lesions involving either the face or neck, airway compromise should be considered. Regional anesthesia is a reasonable technique, as long as the needle insertion site is free of lesions. Traumatic placement of regional anesthesia or invasive monitors can create lesions.


Panniculitis is an inflammatory process that creates deep, tender lesions of fat that tend to expand and ulcerate. Although most common on the trunk and limbs, they can occur on the neck and face with potential airway issues. If generalized inflammation of fat involves fat insulating visceral organs, organ-system dysfunction can result. Perioperative care requires that positioning, regional anesthesia, or invasive monitoring not compromise lesions or increase the risk of infection.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


Pemphigus and pemphigoid are related syndromes characterized by autoimmune blistering of skin and mucous membranes. The bullae are large, soft, and superficial and range in size from 1 to 10 cm at formation. Because they are fragile, they tear easily and leave areas of inflamed, unprotected body surface area. The skin surrounding the lesions is fragile and pressure causes extension of the lesions. Mucous membranes are common sites for lesions, and the oral mucosa is involved in a majority of patients with pemphigoid and in nearly every patient with pemphigus.

The physical cause of the lesions is acantholysis, which is a breakdown of the adherence of the layers of skin and mucous membranes. With pemphigus the superficial layer is not structurally attached and lesions form from minimal trauma. With pemphigoid, the lesions are subepidermal. The lesions of pemphigoid do not extend as easily at their margins as is the case with pemphigus.

Although the most common etiology for pemphigus is idiopathic and autoimmune, there are a variety of other causes, including neonatal transmission, sun exposure, and a variety of drug reactions. The most common drug reactions are to captopril and penicillamine. In contrast to other causes, most drug-induced pemphigus resolves rapidly with elimination of the offending drug. Myasthenia gravis and thymoma have been reported to be associated with pemphigus. Rheumatoid arthritis, lupus, and cirrhosis of the liver have also been associated with pemphigus. Pemphigus may be part of a paraneoplastic syndrome. [371] [372] The oral mucosal lesions of paraneoplastic pemphigus are unusually severe. The triggering neoplasms are most often lymphoma, leukemic, or thymoma. [373] [374] The reverse (pemphigus as a cause of malignancy) is less likely. [375] [376]

Preoperative Considerations ( Table 10-35 ).

Preoperative preparation of patients with pemphigus/pemphigoid focuses on care of the lesions, assessment of the airway, and consequences of treatment. First-line treatment usually begins with high-dose corticosteroid therapy[376] or bolus corticosteroid administration,[377] which should be continued through the perioperative period parenterally to deal with adrenal suppression, as well as avoiding acute exacerbation of the lesions. Dapsone has been used in some patients, but the failure rate, peripheral neuropathy,[378] and hematologic complications (anemia, hemolysis, neutropenia) have made this less common. [375] [380] Rarer complications of dapsone include anaphylaxis, thrombocytopenia, and toxic epidermal necrolyis.[380] Perioperative methemoglobinemia secondary to dapsone has been reported.[381] Some patients may be receiving immunosuppressants,[382] which increase the risk of infection.[380] Because of the nephrotoxicity of some immunosuppressants (cyclosporine), renal function (blood urea nitrogen, creatinine) should be measured. Gold therapy[383] has been used and can cause liver failure,[380] and these patients should have measurement of liver function tests. A combination therapy with tetracycline and nicotinamide has been used[384] and rarely causes renal toxicity and possible acute tubular necrosis.[385] Severe dehydration and electrolyte abnormalities[386] are common in pemphigus patients with lesions covering a large surface area, and assessment of volume status and resuscitation are important preanesthetic issues. In patients with oral lesions, indirect laryngoscopy to evaluate the airway preoperatively would be valuable, recognizing the trauma that could exaggerate oropharyngeal lesions. Coexisting illnesses should be fully explored.[387]

TABLE 10-35   -- Perioperative Issues for Anesthetic Management for Patients with Pemphigoid



Stress-dose corticosteroids



Peripheral neuropathy with treatment (dapsone)



Patient taking immunosuppressants






Laryngeal/airway obstruction



Physical trauma with intubation



Airway obstruction during emergence



Intraoperative Course.

Elective surgery should be rare in these patients.[388] Laryngeal and airway obstruction can be the presentation of pemphigoid requiring anesthetic intervention, and tracheostomy may be required.[389]When emergency surgery is required, management of the airway is potentially life threatening.[390] Intubation could be difficult, and the physical process of placing the endotracheal tube might create lesions that could compromise the airway after extubation. Bleeding within the oropharynx could also result, even from gentle airway instrumentation.[391] Regional anesthesia is possible if the site of the block is free of lesions. [393] [394]


Pemphigus and pemphigoid are autoimmune diseases of the skin that can present issues when surgery/anesthesia is required. Oral lesions are common, and airway compromise is a serious issue. Many of the treatments have issues with major organ systems that must be investigated before surgery. Because these syndromes can be induced into remission or eliminated, elective surgery should be uncommon.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier



Psoriasis is an inflammatory skin disease that results from epidermal proliferation and accumulation. It is the most common chronic disease of the skin. It can be triggered by bacterial or viral infection, bone marrow transplantation,[394] malignancy [396] [397] or emotional stress.


The lesions of psoriasis can be confused with fungal skin lesions and seborrheic dermatitis. There are no significant major organ system issues associated with psoriasis.

Preoperative Preparation.

Chronic corticosteroid therapy is a common management strategy. Stress-dose corticosteroids should be provided for the perioperative period. The surface skin should be inspected to detect any areas of acute infection, which should be treated before elective surgery or regional anesthesia. Uveitis has been reported and could cause visual delay.[397] If immune suppressants are used, [399] [400] [401] [402] renal function should be investigated. If methotrexate is used, liver toxicity should be suspected. [403] [404]

Intraoperative Considerations.

Trauma to psoriatic skin should be avoided. Regional blocks or invasive monitors should not be inserted through psoriatic skin. No specific agents are indicated or contraindicated. Unusual sepsis events have been associated with psoriasis [405] [406] [407] and could present in the operating room or early postoperative period.


Psoriasis is a chronic skin disease that results in large surface areas of inflamed skin. There are no anesthetic issues other than protection of the skin and avoidance of instrumentation of psoriatic skin.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier



Pyoderma gangrenosum (PG) is a destructive inflammatory disease of the skin.[407] The lesion begins as painful nodules that break down and erode into an ulcer.[408] These ulcers naturally expand to large sizes. Some cases are related to other systemic illness, malignancy,[409] or other autoimmune diseases.[410] Neutrophil infiltration of the dermis is causative.[411] Although mucous membranes are usually spared, lesions of the oral cavity, pharynx, and larynx have been reported in a minority of cases.[412] Intradermal injections, intravenous catheters, and surgical incision can cause new lesions. Massive edema from circumferential lesions can be the indication for surgery if distal ischemia or compartment syndrome are present. The lesions can trigger fat necrosis, also causing vascular embarrassment of limbs or panniculitis, which can trigger peritonitis. Polyarthritis can occur, and septic arthritis is an occasional presentation for urgent surgery.[411] An association with vasculitis can also present urgent need for surgery. [414] [415]

Diagnosis ( Table 10-36 ).

The lesions occur as an idiopathic disease confined to the skin in a majority of cases. In the others, a systemic illness proceeds PG and is causative. Myeloma,[415] leukemia, [417] [418] [419] chronic[419]hepatitis, primary[420] biliary cirrhosis, diabetes, carcinoid, lupus, [422] [423] vasculitis, and inflammatory small[423] or large[424] bowel disease are examples of precipitating causes. PG has been associated with allogenic bone marrow transplantation.[425]

TABLE 10-36   -- Causes of Pyoderma Gangrenosum












Biliary cirrhosis















Inflammatory bowel disease



Preoperative Considerations.

Significant lesions around the mouth[426] can occur and should prompt further evaluation to determine if the airway is involved. [428] [429] [430] [431] [432] Because these lesions are associated with other diseases, presurgical preparation should focus on identifying other comorbidities. Inflammatory lesions of the lung can occur and should be investigated if symptomatic. [433] [434] Chronic corticosteroid therapy requires stress-dose corticosteroids in the perioperative period. Some patients are treated with immunosuppressive drugs with organ toxicity, most notably nephrotoxicity and hepatotoxicity with methotrexate.[434] Antimetabolites can induce pancytopenia and/or coagulopathies.

Intraoperative Considerations.

Pressure on existing lesions should be avoided to prevent expansion. Lesions of the oropharynx and airway should be suspected. If abnormality of voice or swallowing is detected, awake fiberoptic intubation is indicated. Regional anesthesia can be used, but the possibility of a lesion occurring at the site of the block must be considered. There is no particular anesthetic agent either indicated or contraindicated. Causative comorbidities may alter the anesthetic course.


Pyoderma gangrenosum is an inflammatory disease of the skin that causes lesions that extend and ulcerate easily. Many systemic illnesses with an inflammatory component can be associated/causative. Lesions of the oropharynx and airway have potentially serious anesthetic implications. Needle puncture and intradermal injections can cause lesions and limit the enthusiasm for regional anesthesia. When general anesthesia is selected, the possibility of lesions of the airway may make awake fiberoptic intubation the best choice.

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Fleisher: Anesthesia and Uncommon Diseases, 5th ed.

Copyright © 2005 Saunders, An Imprint of Elsevier


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