Skin and Bone Disorders

Pathophysiology

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. The pathophysiology is abnormal cartilage formation, particularly at the epiphyseal growth plates. Cellular structure of individual cartilage cells is abnormal. Classification is based on the site of the dysplasia (e.g., epiphyseal, metaphyseal, and diaphyseal). Other terms for 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) ( Table 10-1 ). The etiology is unknown but has been associated with numerous causative factors.

Differential Diagnosis

Another name for achondroplasia is “short-limbed dwarfism.” The achondroplastic appearance is an adult less than 4 feet (1.2 m) tall, with a large head, bulging forehead, depressed nasal bridge, prominent mandible, and short arms and legs with normal trunk size. In those who survive infancy, life expectancy is normal. Affected infants 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. Spinal stenosis can manifest as nerve root compression, cauda equina syndrome, thoracolumbar spinal cord compression, or high cervical cord compression caused by stenosis of the foramen magnum. Quadriplegia in an achondroplastic infant resulted from stenosis of the foramen magnum caused by normal range of motion of the neck. Normal range of motion also caused cervical spinal cord injury in an infant with atlantoaxial subluxation. Quadriplegia occurred after anesthesia and surgery in a diastrophic dwarf with severe kyphosis.

Achondroplasia is an autosomal dominant syndrome, although family history is less obvious because fertility is low. The differential diagnosis of short stature (dwarfism) is based on a combination of clinical and radiographic features. Numerous comorbidities are associated with these syndromes ( Box 10-1 ).

Preoperative Preparation ( Box 10-2 )

Because of the associated congenital defects, abnormalities of the cardiovascular and respiratory systems should be suspected in all patients with chondrodysplasia. Chest radiography, electrocardiography, and transthoracic echocardiography are minimum requirements. Difficult airway management is likely, complicated by anatomic abnormalities of the skull, neck, and chest. Cleft lip, cleft palate, and micrognathia may also be contributing factors. Stridor can occur spontaneously, secondary to laryngomalacia. Symptomatic subglottic stenosis required urgent tracheostomy in one report. The potential for significant atlantoaxial subluxation from abnormal odontoid development or congenital absence of the odontoid 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. If cervical radicular signs are present, or if mental retardation makes recognition impossible, high cervical stenosis should be evaluated 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 (ABG) 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 from kyphoscoliosis secondary to mechanical restriction of thoracic excursion. Tracheomalacia is an additional source of airway compromise and should be evaluated by identification of symptoms, CT, or flow-volume loops. Because of the shape of the head and neck, obstructive sleep apnea is present in as many as 40% of achondroplastic patients, even in childhood. Central sleep apnea has been reported in patients with high cervical spinal stenosis or stenosis of the foramen magnum.

Because no specific treatment exists for achondroplasia, there are no recurring medications. Any medication list is related to comorbidities, such as seizure disorder or lung disease.

Intraoperative Considerations

The primary anesthesia concern in achondroplasia relates to airway management. The high probability of difficult airway management necessitates preparation for awake intubation. Reduced endotracheal tube size has been recommended. 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) can achieve oxygenation and facilitate endotracheal intubation in urgent situations when otherwise impossible in these infants. High spinal cord injury and death have been reported after routine airway management (neck flexion, extension of 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. Pressure-controlled ventilation may be the best approach.

All forms of general and regional anesthesia have been performed in patients with achondroplasia ( Box 10-3 ). Spinal surgery, especially of the cervical spine, may require neurophysiologic monitoring (somatosensory/motor-evoked potentials), which modifies anesthetic options. Regional anesthesia has been reported for achondroplastic patients. Spinal and epidural anesthesia for surgery and obstetrics have been successful, although technically difficult. Successful combined spinal/epidural anesthesia has also been reported. Emergency cesarean section has been accomplished with spinal anesthesia when a difficult airway was obvious. Extensive spread of small volumes of local anesthetic in the epidural space could lead to dangerously high block if the volume injected is not reduced. Peripheral nerve block and plexus block have been accomplished without incident, although the uncontrolled airway management issues associated with local anesthetic–induced seizure activity are a concern. Ultrasound guidance for peripheral and plexus block could reduce this risk. The use of ketamine, succinylcholine, and nitrous oxide for cesarean section has been reported for a full-term achondroplastic parturient who required general anesthesia.

Because of the anatomic and functional abnormality of the chest cage, postoperative ventilatory insufficiency may occur, and extended mechanical ventilation may be necessary. The high probability of obstructive sleep apnea will increase the sensitivity to opioids and make postoperative pain management challenging.

Summary

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

Differential Diagnosis and Clinical Manifestations

Behçet's disease can have a broad differential diagnosis as a result of its myriad manifestations. Oral ulcerations can mimic herpetic stomatitis, pemphigus vulgaris, and Stevens-Johnson syndrome. Skin lesions may be confused with other neutrophilic dermatoses such as Sweet's syndrome, but the triad of iritis, oropharyngeal lesions, and genital mucosal lesions is more specific. CNS involvement can manifest as parenchymal and nonparenchymal disease. Serious manifestations include lesions of the spinal cord and brainstem, cauda equina syndrome, aseptic meningitis, seizures, dementia, coma, and intracranial aneurysms and thrombosis. Dural sinus thrombosis has been reported in a patient with Behçet's disease. Cardiovascular manifestations include myocarditis, vasculitis, pericardial effusion, valve lesions, arterial occlusion, aneurysm, or dissection of major blood vessels. Obstruction of the superior vena cava has been reported, as well as other lesions of major venous structures. Pulmonary manifestations include chronic obstructive pulmonary disease (COPD), hemoptysis, bronchiectasis, pulmonary artery aneurysms and thrombosis, and pulmonary hypertension. Glomerular lesions can precipitate chronic renal failure. In patients with Behçet's involvement of the GI tract, return of GI function may be delayed after surgery. This should also be considered in regard to drug absorption, which can be delayed postoperatively.

Preoperative Preparation ( Box 10-5 )

When Behçet's disease presents as major organ system involvement, these systems should be completely investigated before elective surgery. Severe neurologic manifestations have usually been defined at diagnosis with MRI or CT and should be reviewed for anesthetic issues, including cord compression, increased intracranial pressure (ICP), and 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. If the patient has significant respiratory symptoms, ABG analysis, spirometry, and a chest radiography should be considered. Oropharyngeal ulceration can occur and become symptomatic with onset of hemorrhage. If symptoms such as stridor with exertion suggest airway compromise, indirect laryngoscopy should be considered before elective anesthesia. Blood urea nitrogen (BUN) and creatinine levels should be measured to identify or quantitate chronic renal disease and nephrotoxicity of treatment.

Because Behçet's disease is an inflammatory process, chronic use of anti-inflammatory and antineoplastic drugs such as corticosteroids, azathioprine, cyclosporine, and cyclophosphamide is common. With chronic corticosteroid use, supplemental corticosteroids are necessary the day of surgery.

Intraoperative Considerations

Skin puncture, such as at the site of an intravenous (IV) line, is likely to result in an inflammatory nodule, a phenomenon known as pathergy ( Fig. 10-1 ); punctures should thus be kept to a minimum. Thus, regional anesthesia is less ideal but not contraindicated. With anesthesia of the airway, topical application of local anesthetics is 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. 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 is 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.

Summary

The anesthetic implications of Behçet's disease are related to comorbidity, mainly in the CNS, cardiovascular, and pulmonary systems ( Box 10-6 ). In patients with severe oropharyngeal lesions, airway management can be difficult or impossible. Regional anesthesia can be used, but needle puncture may cause inflammation and lesion formation. General anesthesia is complicated by difficult airway management. Autonomic hyperreflexia is a risk with spinal cord lesions. Spinal involvement can exaggerate the hyperkalemic response to succinylcholine.

Diagnosis

Epidermolysis bullosa is not subtle, and the age of presentation coupled with the diffuse blistering and ulcerations make the diagnosis apparent. The most severe types of recessive DEB involve pseudosyndactyly (“mitten” deformities of hands with scarring contractures and fusion of web spaces), often necessitating corrective surgery. Also, squamous cell carcinomas frequently develop in the sites of chronic ulceration, requiring surgical excision. The pediatric patient with a rare variant of JEB with pyloric atresia may present for surgical repair. Although all surface areas are at risk, each EB patient has areas of the body more affected than others. These sites should be identified preoperatively to allow perioperative protection. 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.

Preoperative Preparation ( Box 10-7 )

The major perioperative issues for EB patients are skin fragility, risk of infection, potential for airway involvement and compromise, chronic malnutrition and impaired GI absorption, potential esophageal strictures from manipulation, and use of nasogastric tubes. Corticosteroids are not often used chronically in these patients, and the need for perioperative corticosteroids should be weighed against the risk for infection. Wound care and infection management or prevention are key elements for survival in EB patients and must be continued carefully in the perioperative period. EB patients with esophageal involvement may have severe dysphasia that can compromise airway reflexes and increase the risk of aspiration during induction or emergence from anesthesia. Significant laryngeal stenosis has been reported with EB. 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.

Intraoperative Care

The key to safe anesthetic care in EB patients is caution with skin and mucous membranes. The blood pressure cuff should be applied over padding and inflated only when needed. Excessive pressure or sustained inflation can cause injury and should be avoided. Placement of monitors must be done with caution. Electrocardiogram (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. Spinal anesthesia for surgery has been reported. Regional anesthesia for surgery or obstetrics can be an excellent choice, as long as the skin at the block site is normal. Successful brachial plexus anesthesia has also been reported in EB patients. Aggressive volume or injecting pressure for infiltration should be avoided because this can cause skin lesions.

With general anesthesia, airway management can be problematic. Prolonged mask ventilation can subject the face to enough friction to cause disfiguring facial lesions; in fact, a variant of JEB (Herlitz type) manifests with prominent perioral granulation tissue and scarring. The physical maneuvers necessary to place an LMA properly would likely 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. This is particularly true with emergency obstetric care. 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. The eyes should not be taped closed, but lubricated. The risk to skin surfaces from stormy emergence makes rapid emergence techniques valuable. Suctioning during emergence should be gentle and limited to direct vision to avoid creating oropharyngeal lesions. With IV drugs, the patency of IV access must be continuously verified, because extravasation can be associated with serious skin injury.

Summary ( Box 10-8 )

The disorders collectively known as epidermolysis bullosa are caused by genetic defects in the skin and mucous membranes that decrease the tensile strength of body surfaces and result in extensive blistering lesions from minimal trauma. Involvement of the esophagus and oropharynx can make airway management difficult, and even minimal trauma from laryngoscopy, stylets, forceful intubation, or blind suctioning can create lesions that compromise the airway. Regional anesthesia can be used as long as the block site is clear of lesions. Excessive volume and pressure with infiltration of local anesthetic for IV placement or nerve block can cause skin injury. Intravenous extravasation is also associated with potential skin sloughing.

Pathophysiology and Clinical Manifestations ( Table 10-3 )

The majority of cases of EM, both minor and major, are triggered by herpes simplex virus (HSV). Less frequently, other infectious agents may be implicated, such as Mycoplasma pneumoniae , Histoplasma capsulatum, and human immunodeficiency virus (HIV). Rarely, a medication may cause EM, but this should heighten clinical suspicion for early presentation of SJS. Also rarely, a response that resembles EM can follow radiation therapy. Both minor EM and major EM manifest with typical target lesions classically described for the disease spectrum. These well-defined, round, 0.5- to 3-cm papules and plaques have a dusky violaceous center and an outer concentric ring of erythema separated by a paler zone. As the lesions progress in number and severity, the central violaceous zone may become bullous, hemorrhagic, or necrotic. EM minor and EM major are distinguished by the presence or absence of mucosal involvement and systemic symptoms, both of which are characteristic of EM major. In general, however, despite the more serious clinical appearance of EM major, both EM conditions are characterized by involvement of relatively minimal body surface area and lack of progression to the SJS/TEN spectrum.

In contrast, SJS and TEN exist on a clinical spectrum together, are characterized by significantly greater involvement of body surface area as well as mucous membranes, an abrupt onset and fulminant course, and most often with cutaneous drug reactions. SJS is classically described as involving less than 10% of body surface area (BSA), whereas TEN involves greater than 30% BSA. The nebulous region between 10% and 30% BSA has been dubbed “SJS-TEN overlap syndrome.” Numerous drugs, including antimicrobials, antiepileptics, and antihypertensives, have been reported as triggers for life-threatening airway compromise from SJS/TEN ( Fig. 10-2 ), caused by mucocutaneous lesions adjacent to the airway and mucous membranes within the airway. Respiratory epithelium is involved in approximately 25% of TEN patients. Conjunctivitis, corneal lesions, and uveitis are common.

Acute myocarditis has been associated with EM triggered by viremia. Mucosal lesions of the trachea or GI tract can cause perforation, resulting in esophageal rupture, mediastinitis, pneumothorax, bronchopleural fistula, or massive GI hemorrhage. Fulminant cases may cause acute renal failure.

Preoperative Preparation ( Box 10-9 )

Erythema multiforme minor presents no unique issues for anesthesiology or surgery. In contrast, EM major, SJS, and TENS are phenomena that can create the need for anesthetic intervention. When time permits, identifying comorbidity may allow optimization, appropriate assessment, or planning, especially if myocarditis or renal failure is known.

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, transepidermal fluid loss can cause hypovolemia and electrolyte imbalances, which should be identified and corrected. Severe chronic cases can be associated with cachexia and malnutrition.

Anesthetic Management

No special anesthetic agents or techniques are indicated in these patients. Barbiturates may precipitate SJS. Skin care is a primary issue; tissue injury from minimal trauma is a risk, and all elements of patient handling must address this concern. 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 and especially with TEN, anesthesia care for airway management is often urgent. All elements of management of the difficult airway may be required, including tracheostomy. 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 eye involvement.

When chronic 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 because of the risk of occult barotrauma. For similar reasons, maximum peak ventilatory pressures should be kept as low as possible. In patients with EM precipitated by oral HSV infection, contamination of anesthesia equipment should be prevented with filters or a disposable circuit and carbon dioxide (CO ₂ ) absorber.

Summary

Erythema multiforme and SJS/TEN present along a clinical spectrum. Minor cases have virtually no anesthetic implications. Patients with severe EM can present for emergency airway management. Most anesthetic management issues are related to comorbidities such as dehydration, electrolyte disturbance, renal failure, myocarditis, and ocular involvement. Most anesthetic techniques are appropriate.

Pathophysiology and Clinical Manifestations

Erythema nodosum (EN), an acute inflammatory reaction of the subcutaneous fat, is the prototypic septal panniculitis. The lesions manifest as red to violaceous, deep, painful nodules most frequently on the anterior legs. Unlike a disease process, EN should be considered a type of hypersensitivity reaction to some other stimulus. The most common causes include infectious or inflammatory processes such as streptococcal pharyngitis, bacterial gastroenteritis, inflammatory bowel disease, and sarcoidosis ( Box 10-10 ). However, despite appropriately thorough investigations for underlying causes, the majority of cases continue to be idiopathic in nature. Less common causes include leptospirosis, toxoplasmosis, Q fever, and sarcoid. A syndrome that resembles EN has been reported as a sequela of malignancy.

Some patients with EN have associated joint involvement, most often 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 may be confused with other forms of panniculitis, such as pancreatic panniculitis and erythema induratum, and with bruising, traumatic fat necrosis, and superficial thrombophlebitis. EN tends to involute spontaneously over several weeks to months, but a more chronic form exists termed erythema nodosum migrans. The lesions of EN rarely ulcerate, and secondary morbidity from EN is uncommon.

Preoperative Preparation

Because the etiology of EN can be infectious, presurgical preparation should focus on identification and treatment of the infectious etiology. In patients who present for emergency surgery (e.g., infectious arthritis), other infections should be considered, but not delaying the surgical procedure. When the precipitating factor is sarcoid, chest radiography and spirometry should be obtained to identify limited pulmonary reserves. ABG 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 ( Box 10-11 )

If respiratory or systemic infections are etiologic, contamination of anesthesia equipment should be prevented with filters or disposable circuit/CO ₂ absorber. Both regional anesthesia and general anesthesia are possible for EN patients, and there are no specific recommendations regarding agents. During acute infection, coincident infection of the airway can cause laryngospasm, bronchospasm, or atelectatic lobar collapse from inspissated secretions.

Summary

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. No specific anesthetic agents or techniques are indicated or contraindicated for EN patients.

Pathophysiology

Fabry's disease results from a congenital defect of glycosphingolipid caused by abnormal function of the enzyme α-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 ( Box 10-12 )

The consequences of lipid accumulation in Fabry's disease include excruciating pain, blue-black vascular lesions of the superficial layers of skin and mucous membranes, and organ dysfunction. The lesions of the mucous membranes usually occur in the mouth and oropharynx. Some cases can occur without surface lesions.

The affected organ systems present with symptoms of organ dysfunction. Cardiac disease presents early in life, including coronary artery disease (CAD), myocarditis, left ventricular hypertrophy, conduction abnormalities, valvular insufficiency, 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. Pulmonary hypertension from lipid accumulation in the pulmonary vasculature can occur. Accumulation of lipid in the kidney causes progressive loss of renal tubular units. 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.

Vascular lesions occur within the CNS and peripheral nervous system. Pain, hyperhidrosis, and GI symptoms can result. Episodic fever is reported. Abnormalities in the brainstem and cerebellum cause disequilibrium and abnormal temperature regulation. Dementia, seizure disorder, and intracranial hemorrhage can occur. Ocular involvement includes corneal opacity, lens involvement, and arterial lesions that can result in retinal artery thrombosis and retinal detachment.