ANORECTAL FISTULA - Timothy L.Black, MD
BASICS
DESCRIPTION
Inflammatory track with one opening in the anal canal and another in perianal skin. Fistulas occur spontaneously or secondary to perirectal abscess. Most fistulas originate in the anal crypts at the anorectal junction.
• Goodsall's rule
- If external opening is anterior to an imaginary line drawn horizontally through anal canal, fistula usually runs directly into anal canal.
- If external opening is posterior to line, fistula usually curves to posterior midline of anal canal.
- For Goodsall's rule: Anterior fistulae, PPV is ~70%, for Posterior fistulae, PPV is ~40%.
- In children, track is usually straight.
• Classification (1)[C]
- Intersphincteric: Fistula is confined to the intersphincteric plane (most common).
- Transsphincteric: Fistula connects intersphincteric plane with ischiorectal fossa by perforating the external sphincter.
- Suprasphincteric: Fistula connects intersphincteric plane with ishiorectal fossa but loops over external sphincter.
- Extrasphincteric: Fistula connects rectum to perineal skin but passes external to sphincter.
• System(s) Affected: Gastrointestinal; Skin/Exocrine
• Synonym(s): Fistula-in-ano; Anal fistula
ALERT
Geriatric Considerations
Constipation is a common complication.
Pediatric Considerations
• Most common in infants
• More frequent in males
GENERAL PREVENTION
Prevention or prompt treatment of anorectal abscess
EPIDEMIOLOGY
• Predominant age: All ages
• Predominant sex: Male = Female
Incidence
Common
RISK FACTORS
• Injection of internal hemorrhoids, puncture wound from eggshells or fish bones, foreign objects, enema tip injuries
• Ruptured anal hematoma
• Prolapsed internal hemorrhoid
• Acute appendicitis, salpingitis, diverticulitis
• Inflammatory bowel disease (chronic ulcerative colitis, Crohn disease)
• Previous perirectal abscess
• Radiation treatment to perineum/pelvis
• Trauma, either internal or external
• Carcinoma
ETIOLOGY
• Erosion of anal canal
• Extension from infection from a tear in lining of anal canal
• Infecting organism is commonly Escherichia coli
ASSOCIATED CONDITIONS
• Possibly associated with penetrating injury, intestinal tuberculosis, ulcerative colitis
• Hidradenitis suppurativa
• Crohn disease
DIAGNOSIS
SIGNS AND SYMPTOMS
• Constant or intermittent drainage or discharge
• Firm tender perianal lump
• External anal sphincter pain during and after defecation
• Spasm of external anal sphincter during and after defecation
• Anal bleeding
• Discoloration of skin surrounding fistula
• Fistulous opening frequently granulose or scarred
• Possible fever
• Recurrent anorectal abscesses in identical locations
History
• History of perianal drainage
• History of perianal pain
• History of recurrent perianal abscesses
Physical Exam
• Perineal or perianal draining orifice
• Recurrent perianal abscesses in identical location
• Small palpable lesion sometimes identified on rectal exam at level of anal crypts
TESTS
Lab
• Complete blood count (usually not indicated)
• Prometheus first step serology for inflammatory bowel disease (if Crohn disease suspected)
• Consider RPR for recurrent fistulas in sexually active patients.
Imaging
• Lower gastrointestinal series if inflammatory bowel disease suspected
• Pelvic MRI or endorectal ultrasound may be useful in complex or recurrent fistulas
Diagnostic Procedures/Surgery
• Proctoscopy
• Sigmoidoscopy
• Probe inserted into tract to determine its course (be careful not to create an artificial opening)
• Injection of dilute methylene blue into abscess cavity may be helpful in demonstrating fistula (1)[C]
Pathological Findings
• Fistulous tract may be simple or multiple
• Fistulous tract has primary opening in anal crypt; secondary opening in anal skin, para-anal skin, perineal skin, or in rectal mucus membrane
• Anal sinus: Opens in anal crypt
• Termination of sinus is blind and located in para-anal or pararectal tissue.
DIFFERENTIAL DIAGNOSIS
• Pilonidal sinus
• Perianal abscess
• Urethroperineal fistulas
• Ischiorectal abscess
• Submucous or high muscular abscess
• Pelvirectal abscess (rare)
• Rule out: Crohn disease; carcinoma; retrorectal tumors
TREATMENT
GENERAL MEASURES
• Appropriate health care: Outpatient surgery
• Sitz baths 3-4 times per day until definitive surgery
Diet
Clear liquid diet until gastrointestinal function returns
Activity
Resume work and normal activity as soon as possible.
MEDICATION (DRUGS)
• Broad-spectrum antibiotic if active infection
- Cephalexin (Keflex)
- Cefadroxil (Duricef)
- Ampicillin-sulbactam (Unasyn)
- Amoxicillin-clavulanate (Augmentin)
• Stool-softening laxative
• Contraindications
- Refer to manufacturer's literature
• Precautions
- Refer to manufacturer's literature
• Significant possible interactions
- Refer to manufacturer's literature
SURGERY
• Fistulotomy
- Surgical incision of entire length of fistula (unroofing) (2)[A]
- Mucosal tract should be cauterized or curetted
- Sphincterotomy
• Fistulectomy
- Complete excision of tract (rarely indicated, because of extensive tissue loss)
- Sphincterotomy
• Consider Seton stitch placement (especially for suprasphincteric or transsphincteric fistulas). (2)[A]
• Endorectal advancement flap closure for complex fistulas. (2)[A]
• General anesthesia or regional anesthesia usually required (usually done as outpatient procedure in children)
• Consider use of fibrin glue in selected cases of anal fistulas (2)[A], (3)[C]
• Fistulas in Crohn Disease (2)[A]
- Asymptomatic fistulas may not need treatment.
- Simple fistulas treated with unroofing
- Complex fistulas treated with advancement flap or long term setons
- May require a stoma
• Postoperative: Sitz baths
• Avoid constipation.
FOLLOW-UP
PROGNOSIS
• Surgical results usually excellent
• Postoperative healing
- 4-5 weeks for perianal fistulas
- 12-16 weeks for deeper fistulas
• Postoperative healing may occur within 2-3 weeks in children.
• Recurrence rates 2-9% in simple fistulas (2)[A]
COMPLICATIONS
• Constipation (urge to defecate may be suppressed due to pain)
• Rectovaginal fistula
• Partial incontinence of fecal material if sphincter is divided
• Delayed wound healing
• Low-grade carcinoma may develop in long-standing fistulas.
• Recurrent anorectal fistula if fistula is incompletely opened or excised
• Chronic intermittent infections
• Sepsis (rarely)
PATIENT MONITORING
Frequent follow-up examinations following surgery to ensure complete healing and assess continence
REFERENCES
1. Townsend C, Beauchamp RD, Evers BM, et al., eds. Sabiston Textbook of Surgery, 17th ed. Philadelphia: Elsevier Saunders; 2006.
2. Whiteford MH, Kilkenny J, Hyman N, et al. Practice parameters for the treatment of perianal abscess and fistula-in-ano (Revised). Dis Colon Rectum. 2005;48:1337-1342.
3. Hammond TM, Grahn MF, Lunniss PJ. Fibrin glue in the management of anal fistulae. Colorectal Dis. 2004;6:308-319.
Wednesday, December 31, 2008
ANORECTAL FISTULA
ANORECTAL ABSCESS
ANORECTAL ABSCESS - Timothy L. Black, MD
BASICS
DESCRIPTION
• Localized induration and fluctuance due to inflammation of the soft tissue near the rectum or anus
• 80% are perianal, the remainder are intrasphincteric or supra-levator (1)[C]
• System(s) Affected: Gastrointestinal; Skin/Exocrine
ALERT
Geriatric Considerations
A high pelvirectal abscess may cause no symptoms except lower abdominal pain and fever.
Pediatric Considerations
Common in first year of life
GENERAL PREVENTION
• Avoid constipation.
• Don't use enemas.
• Avoid rectal temperatures or medicines in immunocompromised patients.
EPIDEMIOLOGY
• Predominant age: All ages (most common in infants) (2)[C]
• Predominant sex: Male > Female (4:1)
Incidence
Common
RISK FACTORS
• Inciting trauma
- Injections for internal hemorrhoids
- Enema tip abrasions
- Puncture wounds from eggshells or fish bones
- Foreign objects
- Prolapsed hemorrhoid
• Inflammatory bowel disease
• Chronic granulomatous disease
• Immunodeficiency disorders
• Hematologic malignancies (5-8% of these patients will have abscess at some time)
• Diabetes
• Chronic medical immunosuppression
ETIOLOGY
• Bacterial invasion of the anal glands found in the intersphincteric space, which may begin with an abrasion or tear in lining of anal canal, rectum, or perianal skin
• Organisms (usually mixed):
- Escherichia coli
- Proteus vulgaris
- Streptococci
- Staphylococci
- Bacteroides
- Pseudomonas aeruginosa
ASSOCIATED CONDITIONS
• Crohn's disease
• Other inflammatory disease (e.g., appendicitis, salpingitis, diverticulitis)
• Possibly perianal hidradenitis suppurativa, or HIV infection in patients with recurring perianal or ischiorectal abscesses
DIAGNOSIS
SIGNS AND SYMPTOMS
• Perirectal swelling for superficial abscesses
• Perirectal redness
• Perirectal tenderness
• Perirectal throbbing pain
• Fever and other toxic symptoms with deep abscesses
• If abscess is not accompanied by external swelling, digital rectal exam will reveal a swollen tender mass.
• Pain on defecation
Physical Exam
Digital rectal examination is mandatory
TESTS
Lab
Complete blood count: Leukocytosis
Imaging
• Barium enema (rarely needed)
• CT scan of pelvis and perineum indicated if horseshoe or ischiorectal abscess suspected (3)[C]
Diagnostic Procedures/Surgery
Only indicated if diagnosis in doubt
• Sigmoidoscopy: Rule out unusual causes
• Proctoscopy: Redness, induration of anus; tender mass
Pathological Findings
• Inflammation of anal mucosa
• Pus
• Inflammatory tissue
DIFFERENTIAL DIAGNOSIS
• Carcinoma
• Retrorectal tumors
• Crohn's disease
• Primary lesions of syphilis
• Tuberculous ulceration
TREATMENT
GENERAL MEASURES
Appropriate health care
• Outpatient surgery with oral antibiotics (although in some cases, antibiotics may not be necessary) (4)[B]
• Inpatient surgery with IV antibiotics for supra-levator abscess or toxicity (3)[C]
Diet
Increase fiber and fluid intake.
Activity
Resume work and normal activity as soon as possible.
MEDICATION (DRUGS)
• Antibiotics
• Stool-softening laxatives
• Contraindications
- Refer to manufacturer's literature
• Precautions
- Refer to manufacturer's literature
• Significant possible interactions
- Refer to manufacturer's literature
SURGERY
• Perianal abscess
- Incise and drain abscess (4)[B]
- Local anesthetic frequently appropriate
- Pack wound with Iodoform gauze (24-48 hours).
• Ischiorectal abscess
- Incise and drain abscess (4)[B]
- General anesthetic usually required
- Pack wound with Iodoform gauze or similar packing (removed gradually over several days).
- Fistulectomy may be done at the same time in selected cases.
• Supralevator abscess
- Incise and drain abscess into lower rectum or anal canal (3)[C]
- General anesthesia required
• After surgery
- Sitz baths q2-4h
- Heating pad, heat lamp, or warm compress as needed for pain
- Encourage moving legs as soon as possible
- Prevent constipation.
FOLLOW-UP
PROGNOSIS
• Slow healing depending on extent of disease and concurrent illnesses, complete healing by 6 months if no complications
• Healing in infants may be complete in 1-3 weeks.
• Drainage alone results in cure rate of 50% or more.
COMPLICATIONS
• Possible anorectal fistula (in 25% of patients) (2,3)[C]
• Possible rectovaginal fistula
• Fecal incontinence due to rupture through sphincter muscle
• Recurrence of abscess if underlying cause not corrected
• Necrotizing infection with rapid progression, sepsis, and death (3)[C]
PATIENT MONITORING
Routine postoperative care with attention to wound healing, which should progress from the inside out
REFERENCES
1. Fazio VW. Anorectal disorders. In: Gastroenterology Clinics of North America. Philadelphia: Saunders; 1987.
2. Ziegler M, Azizkhan R, Weber T, et al., eds. Operative Pediatric Surgery. New York: McGraw-Hill, 2003
3. Townsend C, Beauchamp RD, Evers BM, et al. eds. Sabiston Textbook of Surgery, 17 ed. Philadelphia: Elsevier Saunders, 2006
4. Whiteford MH, Kilkenny J, Hyman N, et al. Practice parameters for the treatment of perianal abscess and fistula-in-ano (revised). Dis Colon Rectum 2005;48:1337-1342.
ANKYLOSING SPONDYLITIS
ANKYLOSING SPONDYLITIS - Jane S. Kim, MD
BASICS
DESCRIPTION
Ankylosing spondylitis (AS) is a chronic inflammatory seronegative arthritis affecting the axial skeleton with primary involvement of the sacroiliac joint.
• System(s) Affected: Musculoskeletal
• Synonym(s): Rheumatoid spondylitis; Marie-Strumpell disease
EPIDEMIOLOGY
• Predominant age: Onset usually in early 20s, rarely occurs after age >40 years of age
• Predominant sex: Male > Female (3:1)
Incidence
• In white males: 0.5-5 per 1,000
• Less common in women and African Americans
Prevalence
0.1-0.2% in United States
RISK FACTORS
• HLA-B27 (1% of HLA-B27-positive adults likely to have AS)
• Positive family history
- 10% risk of developing AS for HLA-B27-positive child of spondylitic parent
Genetics
Familial clustering and higher than expected frequency of HLA-B27 tissue antigen
PATHOPHYSIOLOGY
Inflammation at the insertion of tendons causes new bone formation (enthesitis).
ETIOLOGY
Unknown
ASSOCIATED CONDITIONS
• Uveitis (25-30%)
• Iritis
• Psoriasis
• Aortic insufficiency (2%)
DIAGNOSIS
SIGNS AND SYMPTOMS
History
• Insidious onset
• Duration >3 months
• Morning stiffness
• Frequently awaken at night to "walk off" stiffness
• Improvement in stiffness with activity
• Increased symptoms with rest
• Hip, shoulder, or knee complaints
• Constitutional symptoms (fatigue, weight loss, low-grade fever)
Physical Exam
• Subgluteal or low back pain and/or stiffness
• Pleuritic chest pain often an early feature
• Diminished range of motion in the lumbar spine in all three planes of motion
• Loss of lumbar lordosis
• Thoracocervical kyphosis (rarely occurs before 10 years of symptoms)
• Aortic regurgitation murmur (1%)
• Acute anterior uveitis
• Osteoporosis
• Plantar fasciitis
• Peripheral arthritis (20-30%)
TESTS
• Synovial fluid: Mild leukocytosis, decreased viscosity
• EKG: Conduction defects
• Measurement of respiratory excursion of chest wall: 5 cm maximal respiratory excursion of chest wall measured at fourth intercostal space
• 2.5 cm is virtually diagnostic of ankylosing spondylitis
• Wright-Schober test for lumbar spine flexion is abnormal or 5 cm.
- Mark the patient's back over the L5 spinous process and 10 cm above this point, then have the patient bend forward.The distance between the 2 marks should increase by 5 cm or more in normal persons.
Lab
• The HLA-B27 tissue antigen is present in 90% of White AS patients; there is a 5-8% incidence in the general population.
• ESR and CRP are elevated in the majority of the cases but correlate poorly with disease activity and prognosis. Mild elevation in serum IgA, creatine kinase, alkaline phosphatase, and complement may be seen.
• Absent rheumatoid factor
• Mild normochromic anemia (15%)
Imaging
• Sacroiliac joint early: Sclerosis on both sides of joint not extending >1 cm from articular surface = sacroiliitis
• Sacroiliac joint late
- Ankylosis of sacroiliac joint
- Osteopenia
• Spine
- "Squaring" of vertebral bodies and ossification of annulus fibrosis giving appearance of "bamboo spine"
- Ankylosis of facet joints
• Peripheral joint
- Symmetric erosive changes in larger joints
- Pericapsular ossification, sclerosis, loss of joint space
• Preferred position for imaging the SI joints with plain films is oblique projection. MRI of the SI joints may show increased signal from the bone and bone marrow suggesting osteitis and edema.
Diagnostic Procedures/Surgery
• Physical examination
• Radiographs: Sacroiliac joint films, lumbar spine series
• DEXA bone scan (high incidence of osteoporosis)
• MRI may show early enthesitis.
Pathological Findings
• Erosive changes coupled with new bone formation at the attachment of the tendons and ligaments to the bone resulting in ossification of periarticular soft tissues
• Synovial changes are indistinguishable from rheumatoid arthritis.
• Erosion of articular cartilage is less severe than in rheumatoid arthritis.
DIFFERENTIAL DIAGNOSIS
• Reactive arthritis
• Psoriatic arthritis
• Diffuse idiopathic skeletal hypertrophy (DISH)
• Spondylitis associated with inflammatory bowel disease
• Rheumatoid arthritis
TREATMENT
GENERAL MEASURES
• Appropriate healthcare: Outpatient
• Posture training and range of motion exercises for spine are essential.
• Firm bed
• Sleep in supine position without a pillow
• Breathing exercises 2-3 a day
• Smoking cessation
Activity
• Encourage active lifestyle. Swimming, tai chi, and walking are recommended.
• Avoid trauma/contact sports.
• Avoid prolonged standing.
SPECIAL THERAPY
Physical Therapy
Exercises to improve posture and flexibility
MEDICATION (DRUGS)
First Line
• NSAIDs provide symptomatic relief, usually rapidly.
- A dramatic response to NSAIDs can be diagnostic of AS.
• Selection is empiric, but traditionally indomethacin 50 mg t.i.d. or q.i.d. has been used.
• Intra-articular steroid injections may provide relief though systemic corticosteroids typically do not.
• Osteoporosis prophylaxis and treatment
• Injection of a long-acting corticosteroid into the sacroiliac joints may be beneficial in very symptomatic patients. Avoid systemic corticosteroids.
• Precautions
- All patients on long-term NSAIDs should have their renal function monitored.
- NSAIDs may aggravate peptic ulcer disease or cause gastritis.
- NSAIDs should be used with caution in patients with a bleeding diathesis or patients requiring anticoagulants.
- Refer to the manufacturer's profile of each drug for significant possible interactions.
Second Line
• Used when patients fail NSAIDs or become intolerant of them
• Sulfasalazine and methotrexate caused clinical improvement.
• Etanercept (anti-tumor necrosis factor alpha agent) showed rapid, significant, and sustained improvement and is now FDA-approved for AS. (2)[A]
• Infliximab can be efficacious and is also FDA-approved for AS. (4)[A]
• Thalidomide shows promise. (3)[C]
• Pamidronate may also help function and decrease disease activity. (3)[C]
SURGERY
• Total hip replacement should be considered to restore upright posture and to control pain in severe cases.
• Vertebral osteotomy can improve posture for those patients with severe cervical flexion.
FOLLOW-UP
DISPOSITION
Issues for Referral
Rheumatologists will be experienced in diagnosing and treating AS.
PROGNOSIS
• Unpredictable course
• Prognosis good if mobility and upright posture maintained
• Usually progressive disability
• No difference in overall mortality
COMPLICATIONS
• Spine
- Spinal fusion causing kyphosis
- Cervical spine fracture (high mortality rate)
- C1-C2 subluxation
- Cauda equina syndrome (rare)
• Peripheral joint ankylosis
• Pulmonary
- Restrictive lung disease
- Upper lobe fibrosis (rare)
• Cardiac
- Conduction defects
- Aortic insufficiency
- Aortitis
- Pericarditis
• Uveitis and cataracts
• Renal
- IgA nephropathy
- Amyloidosis (rare)
• Cutaneous LCV (rare)
• Gastrointestinal: Illeal and colonic mucosal ulcerations, mostly asymptomatic
PATIENT MONITORING
Visits every 6-12 months to monitor posture and range of motion
REFERENCES
1. Bennett DL, Ohashi K, El-Khoury GY. Spondyloarthropathies: Ankylosing spondylitis and psoriatic arthritis. Radiol Clin North Am. 2004;42(1):121-134.
2. Gorman JD, Sack KE, Davis JC Jr. Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha. N Engl J Med. 2002;346:1349-1356.
3. Davis JC Jr, Huang F, Maksymowych W. New therapies for ankylosing spondylitis: Etanercept, thalidomide, and pamidronate. Rheum Dis Clin North Am. 2003;29:481-494.
4. De Keyser F, Baeten D, Van den Bosch F, Kruithof E, Mielants H, Veys EM. Infliximab in patients who have spondyloarpthropathy: Clinical efficacy, safety, and biological immunomodulation. Rheum Dis Clin North Am. 2003;29(3):463-479.
5. Kataria RK, Brent LH. Spondyloarthropathies. Am Fam Phys. 2004;69(12):2853-2860.
ANKLE FRACTURES
ANKLE FRACTURES - Heather C. Killie, MD
BASICS
DESCRIPTION
• Fractures involving the distal fibula (lateral malleolus) and/or distal tibia (medial malleolus and plafond)
• Includes a range of injuries to bones and ligaments of the ankle
GENERAL PREVENTION
• Proper shoe wear (i.e., flat, supportive shoes)
• Avoid running or walking on uneven or slick surfaces.
EPIDEMIOLOGY
• One of the most common fractures requiring orthopedic care
• Lateral malleolus more commonly involved (account for 2/3 of all ankle fractures)
Incidence
• Age-specific incidence increases in men >60 and women >50 years of age
• Highest incidence in elderly women (1)[B]
ALERT
Pediatric Considerations
• Pediatric will present with fractures involving the growth plates
• Most commonly a Salter-Harris I fracture of the distal fibula
RISK FACTORS
• Increased body mass index
• History of smoking
• No association between general health and risk for ankle fracture
PATHOPHYSIOLOGY
The location and pattern of injury depend on foot position and the direction of force applied. Most commonly the foot is plantarflexed and inverted, and the force is external rotation.
Axial load can cause a tibial plafond (a.k.a. pilon) fracture, which is an intra-articular fracture of the distal tibia where it articulates with the talus.
ETIOLOGY
Fall or twisting injury to the ankle
ASSOCIATED CONDITIONS
• Ankle sprains
• Syndesmosis injury
• Ankle or subtalar dislocation
• Fracture of the metatarsals, talus, calcaneus
• Osteochondral fracture (subchondral fracture of the distal tibia or talus)
• Neurovascular injury (very rare)
DIAGNOSIS
PRE HOSPITAL
• If ankle is obviously deformed, it should be reduced and provisionally splinted after adequate pain control is achieved.
• Place ice on ankle and elevate extremity
SIGNS AND SYMPTOMS
• Pain, swelling, and ecchymosis
• Pain or inability to bear weight
• Possible deformity
History
• Mechanism of injury
- Fall or twisting injury
• Timing of injury
• Past history of ankle injuries
• Any other injuries sustained
Physical Exam
• Inspect the ankle and foot for swelling and ecchymosis.
• Inspect the skin for tenting or lacerations.
• Palpate dorsalis pedis and posterior tibial pulses
• Palpate medial and lateral malleoli, proximal leg, and foot
• Sensory and motor exam of ankle and foot
• Rule out compartment syndrome (very rare), especially of the deep posterior compartment of the leg.
TESTS
Lab
Routine lab studies are not needed unless the fracture is operative.
Imaging
• Ottawa Ankle Rules help the clinician determine when to get x-rays. (2)[A]
• X-rays when patient has pain at either malleoli and 1 or more of following:
- Age >55
- Inability to bear weight
- Bony tenderness at posterior edge or tip of either malleoli
• 3 standard views: AP, Lateral, Mortise (15 internal rotation view)
• When foot pain present, get 3 views of foot
Diagnostic Procedures/Surgery
• Arthroscopy is an option in cases of persistent pain or suspicion of an OCD lesion.
• Open reduction, internal fixation in cases of instability (See "Treatment" section)
DIFFERENTIAL DIAGNOSIS
• Stress fracture
• Ankle sprain
• Osteochondral fracture
• Talus fracture
• 5th Metatarsal fracture
• Calcaneus fracture
TREATMENT
PRE-HOSPITAL
• If ankle is obviously deformed, it should be reduced with adequate pain control and provisionally splinted per first-aid protocol.
• Ice and elevate the extremity.
STABILIZATION
• As above if obvious deformity
• Place leg in a padded posterior splint to include toes to just below knee.
• If the fracture is open, remove any debris from the wound, place a moist dressing over the wound, and immediately contact an orthopedic surgeon.
• Obtain x-rays.
GENERAL MEASURES
Activity
• Non-weight bearing in all fractures
• EXCEPTION
- Isolated avulsion fractures of the tip of the lateral malleolus may be weight bearing as tolerated.
Nursing
• Apply ice.
• Instruct patient to keep leg elevated
• Control pain.
SPECIAL THERAPY
Physical Therapy
Early range of motion is key to prevent stiffness.
• Encourage toe and knee motion as soon as possible.
• Start ankle ROM as soon as there is evidence of fracture healing (usually 6 weeks).
MEDICATION (DRUGS)
• In general, ankle fractures are painful, particularly in the 1st 5-7 days following an injury. As the swelling decreases, so does the pain.
First Line
• Acetaminophen
• Opiod analgesics (i.e., hydrocodone)
• Avoid NSAIDs acutely (may delay healing of fractures)
Second Line
Non-opiod analgesics (i.e., tramadol)
SURGERY
• Absolute surgical indications
- Open fractures (fix within 6-8 hours)
• Relative surgical indications
- Gross instability (i.e., dislocation on presentation, bi- or tri-malleolar ankle fractures)
- Displacement after closed reduction attempt
- Displaced, comminuted distal tibia fractures
• Surgical options
- Open reduction internal fixation with plates and screws (most commonly)
- External fixation for comminuted distal tibia fractures
• Timing of surgery
- Within 6-8 hours if skin open
- After swelling decreased in all other cases (preferably not >1 week)
• Length of recovery
- In general, 6-8 weeks for healing
- 6-8 weeks in a cast or splint (longer if fracture involves both medial and lateral malleoli)
- 2-4 months for syndesmotic injury
- Orthopedist may allow range of motion after 4 weeks and place in removable cast boot (fracture pattern and surgeon dependent)
FOLLOW-UP
Most ankle fractures require close follow-up by an orthopedic surgeon (see "Referral" section)
DISPOSITION
• Patient should be transferred to the emergency department if
- Open fractures
- Dislocated ankle
- Neurovascular injury
- Possible compartment syndrome
• Otherwise, patient should be referred to an orthopedic surgeon
Admission Criteria
Admit to the hospital if
Open fracture
Neurovascular injury
Cannot maintain non-weight bearing status and requires physical therapy consultation
Concern of skin compromise
Concern of mechanism of injury (i.e., syncope, MI, head injury)
Discharge Criteria
When patient has completed the following
Able to ambulate with walker/crutches
Medical work-up (if needed) is completed
Appropriate orthopedic follow-up is arranged
Elderly patients may require a short stay in a rehabilitation facility.
Issues for Referral
• Most ankle fractures should be seen by an orthopedic surgeon within 5-7 days, earlier if a reduction is needed.
• Open fractures should be seen by an orthopedic surgeon immediately.
PROGNOSIS
• Good results can be achieved in most ankle fractures without surgery, provided the ankle mortise is maintained. (3)[B]
• Long term, some patients may develop ankle arthritis; timing is unpredictable.
• Effusion or pain can persist for up to 1 year.
COMPLICATIONS
• Non-operative
- Displacement of the fracture
- Malunion
- Skin breakdown
- DVT (rarely pulmonary embolism)
• Operative
- Infection
- Loss of fixation
- Nonunion or malunion
- Skin breakdown
- DVT (rarely pulmonary embolism)
PATIENT MONITORING
• Serial x-rays should be performed weekly for 4 weeks if there is any question about stability.
• Otherwise, x-rays should be performed at 2 weeks, 4 weeks, and 8 weeks or until the fracture is healed.
REFERENCES
1. Court-Brown CM, McBirnie J, Wilson G. Adult ankle fracturesan increasing problem? Acta Orthop Scand. 1998;69(1):43-47.
2. Stiell IG, Greenberg GH, McKnight RD, et, al. Decision rules for the use of radiography in acute ankle injuries: Refinement and prospective validation. JAMA. Mar 1993;269:1127-1132.
3. Michelson JD. Ankle fractures resulting from rotational injuries. J Am Acad Orthop Surg. 2003;11:403-412.
ANIMAL BITES
ANIMAL BITES - George R. Bergus, MD
BASICS
DESCRIPTION
• Bite wounds to humans from dogs, cats, other animals including humans
• System(s) Affected: Endocrine/Metabolic; Hemic/Lymphatic/Immunologic; Nervous; Skin/Exocrine
ALERT
Geriatric Considerations
• Serious injury from any bite wound is more common >50 years old, those with wounds in the upper extremities, or those with puncture wounds.
• Increased risk of infection >50 years old
Pediatric Considerations
Young children are more likely to have severe bites.
GENERAL PREVENTION
• Instruct children and adults about animal hazards.
• Educate dog owners about responsible dog ownership.
• Strongly enforce animal control laws.
EPIDEMIOLOGY
Incidence
• Dog bites: 1,200/100,000
• Cat bites: 160/100,000
• Snake bites: 15/100,000 nonvenomous bites and 3/100,000 venomous bites per year
• Lifetime prevalence for animal bite: 50,000/100,000
• Dog bites are responsible for 1/3 million emergency room visits per year
Prevalence
• Predominant age: All ages, but children more likely to be affected
• Predominant sex: Male > Female
RISK FACTORS
• Dog bites are more common during warm weather.
• Male dogs are more likely to bite.
• Clenched-fist injuries are frequently associated with the use of alcohol.
ETIOLOGY
• Most bite wounds are from a domestic pet known to the victim.
• Large dogs are the most common source of bite wounds.
• Human bites are often the result of one person striking another in the mouth with a clenched fist.
DIAGNOSIS
SIGNS AND SYMPTOMS
• Bite wounds can be tears, punctures, scratches, avulsions, or crush injuries.
• Dog bites (80-90% of bites)
- In adults, hands are most commonly affected.
- In children, the face is the most common site of injury, and involvement of the trunk is uncommon.
• Cat bites (10% of bites)
- Predominantly involve the hands, followed by lower extremities, face, and trunk
- Are more likely to become infected because of puncture nature of wounds
TESTS
Lab
• 85% of bite wounds will yield a positive culture, but culturing at time of injury is of little benefit
• Wound culture is essential in directing therapy.
- Some pathogens are slow growing, so cultures should be kept for 7-10 days
- Gram stain is sensitive but not specific for infecting organism
• Dog bites
- Pasteurella species is present in 50% of bites.
- Also found: Streptococcus viridans, Staphylococcus aureus, coagulase-negative Staphylococcus, Bacteroides, Capnocytophaga canimorsus, Fusobacterium
• Cat bites
- Pasteurella species is present in 75% of bites.
- The wound is often contaminated by other mixed bacteria, including several species of both aerobic and anaerobic organisms.
• Human bites
- Streptococcus species, Staphylococcus aureus, Eikenella corrodens, and various anaerobic bacteria are very common.
• Other animal bites
- Scant information on pathogens
• Drugs that may alter lab results
- Previous antibiotic therapy
Imaging
• If bite wound is near a bone or joint, a plain radiograph is needed to check for bone injury and to use for comparison later if osteomyelitis is suspected.
• In human bite wounds from clenched-fist injuries, order plain-film radiographs to check for metacarpal or phalanx fracture.
Diagnostic Procedures/Surgery
• Consider rabies prophylaxis for bats, nondomestic dogs; rarely skunks, foxes and raccoon
• Surgical exploration may be needed to ascertain extent of injuries.
• Exploration should be performed on all serious hand wounds, especially clenched-fist injuries involving a joint.
DIFFERENTIAL DIAGNOSIS
Diagnosis is straightforward; what is of concern is judging the risk to the patient from the injury and resulting infection.
TREATMENT
GENERAL MEASURES
• Appropriate health care: Outpatient, unless patient has fulminant infection requiring systemic antibiotics, close observation, or surgery
• Elevation of the injured extremity to prevent swelling
• Contact the local health department and consult about the prevalence of rabies in the species of animal involved.
MEDICATION (DRUGS)
First Line
• Consider antirabies therapy.
• Use tetanus toxoid in those previously immunized, but >5 years since their last dose.
• Consider tetanus immune globulin (TIG) in patients without a full primary series of immunizations.
• Prophylactic therapy if wound seen in 1st 12 hours
- Dog, cat, or animal: Amoxicillin-clavulanate 500-875 mg b.i.d. PO (pediatric: 20-40 mg/kg/d PO given t.i.d.)
- Snake bite: If venomous, the patient needs rapid transport to a facility capable of definitive evaluation. If an envenomation has occurred, the patient will need to receive antivenin unless envenomation was only minimal. Be sure patient is stable for transport; consider measuring and or treating coagulation and renal status along with any anaphylactic reactions before transport.
- Human bites: Amoxicillin-clavulanate (Augmentin) potassium, adult: 500 mg PO t.i.d. (pediatric: 20-40 mg/kg/d PO given t.i.d.)
• Established infection
- After patient has developed a clinical infection, amoxicillin-clavulanate potassium (Augmentin) can be used pending culture reports
• Contraindications: Do not use penicillin-derived antibiotics in those with penicillin allergy.
• Precautions: Prescribe dosage of antibiotics by body weight and renal function.
• Significant possible interactions: Antibiotics may decrease efficacy of oral contraceptives
Second Line
• Alternative therapy for penicillin-allergic patients (for prophylaxis or empiric treatment)
- ~10% cross-reactivity with cephalosporins in penicillin-allergic patients
- Dog bite: Moxifloxacin 400 mg/day 7 days in adults (pediatric: trimethoprim- sulfamethoxazole along with Clindamycin); avoid cephalexin due to resistant strains of Pasteurella multocida
- Cat bite: As for dog bite
- Human bite: Moxifloxacin 400 mg/day
• If hospitalized with established infection: Ampicillin-sulbactam (Unasyn) 1-2 g IV q6h or ticarcillin-clavulanate (Timentin) 3.1 g IV q4-6h
SURGERY
• Copious irrigation of the wound with normal saline via a catheter tip is needed to reduce risk of infection.
• Devitalized tissue needs debridement.
• Debridement of puncture wounds not advised.
• Consider surgical closure if the wound is clean after irrigation and bite is 12 hours old. Puncture wounds should be left open.
• Delayed primary closure in 3-5 days is an option for infected wounds.
• Splint hand if it is injured.
• Human bite wounds on the hands should not be primarily closed because of the high risk of infection. Large, gaping wounds should be reapproximated with widely spaced sutures or Steri-Strips.
FOLLOW-UP
PROGNOSIS
Wounds should steadily improve and close over by 7-10 days.
COMPLICATIONS
• Septic arthritis
• Osteomyelitis
• Extensive soft tissue injuries with scarring
• Sepsis
• Hemorrhage
• Death
• Gas gangrene can take an exceedingly rapid course and should be treated very aggressively.
PATIENT MONITORING
• Patient should be re-checked in 24-48 hours if not infected at time of 1st encounter
• Daily follow-up is warranted with active infections.
• If antibiotics are used for an active infection, the duration of therapy should be 7-14 days, depending on the severity of the infection and the clinical response.
REFERENCES
1. Stevens DL, et al. Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin Infect Dis. 2005;41(10):1373-1406.
2. Fleisher GR. The management of bite wounds. N Engl J Med. 1999:340:138-140.
3. Griego RD, et al. Dog, cat and human bites: A review. J Am Acad Dermatol. 1995;33: 1019-1029.
4. Presutti RJ. Prevention and treatment of dog bites. Am Fam Physician. 2001;63(8):1567-1572, 1573-1574.
5. Sacks JJ, et al. Fatal dog attacks 1989-1994. Pediatrics. 1996;97:891-895.
MISCELLANEOUS
Rabies
• Contact your local health department for information about the risk of rabies.
• Most human rabies are related to bat bites. See also: Bartonella Infections; Cellulitis; Rabies; Snake Envenomations; Crotalidae; Elapidae
ANGIOEDEMA
ANGIOEDEMA - Anatoli Freiman, MD
BASICS
DESCRIPTION
• Dermal (subcutaneous or submucosal) extravasation of fluid, leading to localized edema
• The release of inflammatory vasoactive mediators increases vascular permeability.
• The skin, gastrointestinal tract, and respiratory tract are most commonly involved. It is life threatening if the upper airway is affected. It usually resolves in hours to days.
• Can be idiopathic or induced by medications, allergens (e.g., food), or physical agents (e.g., vibration, cold)
• 2 rare but well-described categories of angioedema result from deficiency of C1 esterase inhibitor (C1 INH) of the compliment and kallikrein-kinin systems: Hereditary angioedema (HAE) and acquired angioedema (AAE).
- HAE type I (80-85%): Due to hereditary deficiency of C1-INH; recurrent episodes of angioedema, involving both skin and mucous membranes or intestinal mucosa (25% mortality)
- HAE type II (15-20%): Normal or elevated quantities of functionally impaired C1-INH
- HAE type III: Rare, recently described estrogen-dependent form
- AAE type I: Increased destruction of C1-INH, which occurs in patients with rheumatologic disorders and B-cell lymphoproliferative malignancies, such as leukemia, T-cell lymphoma, multiple myeloma, and essential cryoglobulinemia
- AAE type I is also reported with carcinomas, infections, and vasculitides. Immune complexes continuously activate C1, leading to consumption of C1-INH and precipitating angioedema.
- AAE type II: B cells secrete autoantibodies against C1-INH, leading to its inactivation
• Medication-induced angioedema
- Immunologic hypersensitivity, as in penicillin reaction
- Nonimmunologic, as in reactions to NSAIDs (e.g., aspirin)
- Angiotensin converting enzyme (ACE) inhibitors decrease levels of angiotensin II and stimulate production of bradykinin, a potent vasodilator, thus leading to angioedema. This may occur immediately or months after starting the drug.
• System(s) Affected: Skin/Exocrine
• Synonym(s): Angioneurotic edema; Quincke edema
GENERAL PREVENTION
• If etiology known, avoidance
• Avoid ACE inhibitors in patients with a history of angioedema.
EPIDEMIOLOGY
• Predominant age
- HAE: Infancy to second decade of life
- AAE: Typically patients > 40 years old.
• Predominant sex: Male = Female (idiopathic)
Incidence
• 1 in 5,000
• Accompanies urticaria 40-50% of time
RISK FACTORS
• Medications and foods that can cause allergic reactions
• ACE inhibitors are contraindicated in patients with C1-INH deficiency
Genetics
HAE types I and II are inherited in autosomal dominant mode, whereas type III is X-linked. HAE occurs in 25% of the patients as a result of spontaneous mutations.
PATHOPHYSIOLOGY
Similar pathophysiology for urticaria and angioedema: Localized anaphylaxis causes vasodilatation and vascular permeability of superficial (urticaria) or subcutaneous/deeper dermal tissue (angioedema)
ETIOLOGY
• Idiopathic
• Medication-induced: ACE inhibitors, NSAIDs, antibiotics, or estrogen contraceptives
- ACE inhibitors (ACEI) are ascribed to 10-25% of angioedema cases and mostly occur within the 1st 3-4 weeks of use. However, the 1st onset may be delayed years. Failure to react to re-challenge with drug does not rule out a cause-effect relationship between the ACEI and angioedema.
- Losartan (Cozaar), valsartan (Diovan), and irbesartan (Avapro), which are all angiotensin receptor blockers (ARB), can also cause angioedema. It can occur within 24 hours to 16 months after initiating losartan therapy.
• Allergen-induced: Food allergens, such as fish, nuts, and preservatives
• Physically induced: Cold, pressure, vibration
• Hereditary or acquired C1-INH deficiency
• Thyroid autoimmunity has been reported to be associated with angioedema.
ASSOCIATED CONDITIONS
• Urticaria
• Anaphylaxis
DIAGNOSIS
SIGNS AND SYMPTOMS
• Occurs alone or in association with urticaria in 50% of cases
• Angioedema usually does not cause itching in comparison to urticaria, but can cause burning.
• Relatively rapid onset of presentation; usually resolves spontaneously in 72 hours
• Skin
- Localized swelling; may occur anywhere on body; usually face, extremities, or genitalia; often asymmetric
- Frequently disfiguring and frightening to the patient
• Gastrointestinal
- May present with intermittent unexplained abdominal pain
• Respiratory
- May be associated with generalized anaphylactic reaction, potentially fatal if upper airway is compromised
History
• Acute onset of asymmetric localized swelling
• GI tract involvement may manifest as intermittent unexplained abdominal pain.
• In comparison to urticaria, angioedema is typically nonpruritic, but can cause burning.
Physical Exam
Subcutaneous swelling, usually of the face (eyelids, lips, ears, nose), and less often of the extremities or genitalia
TESTS
Lab
• If angioedema with urticaria and/or anaphylaxis, no testing is needed, but history should be directed to exposures: Foods, medications, exposures, etc.
• Without clear etiology and recurrence in angioedema and urticaria, CBC and ESR; macrocytosis implies a pernicious anemia; eosinophilia my imply atopy or rarely parasitic infection. Elevated ESR may imply systemic disorders.
• In recurrent angioedema without clear etiology and without urticaria, consider ordering C4. Low serum C4 is a very sensitive, but nonspecific, screening test for hereditary and acquired C1-INH deficiency. If C4 is normal, urticaria work-up is recommended.
• If C4 is low, C1-INH assay (immunoreactive) is performed for HAE type I and C1-INH assay (functional) for HAE type II.
• C1q is decreased in acquired C1-INH deficiency.
• If C4 and C1q are low (as in AAE), neoplastic and autoimmune work-up are warranted. Routine blood tests, a smear, protein electrophoresis, immunophenotyping of lymphocytes, and imaging studies are often undertaken to rule out hematological malignancies or cancer.
• May alter lab results
- Antihistamines
- H2-blockers
- Tricyclic antidepressants
Imaging
As part of neoplastic work-up if relevant
Diagnostic Procedures/Surgery
Skin biopsy (may be nonspecific)
Pathological Findings
Edema of deep dermis and subcutaneous tissue. Variable perivascular and interstitial infiltrate
DIFFERENTIAL DIAGNOSIS
• Urticaria
• Allergic contact dermatitis
• Connective tissue disease: Lupus, dermatomyositis
• Anaphylaxis
• Cellulitis, erysipelas
• Lymphedema
• Diffuse subcutaneous infiltrative process
TREATMENT
PRE-HOSPITAL
• Ensure airway patency 1st! Protect the airway if the mouth, tongue, and/or throat are involved.
• Perform CPR and transport to an emergency facility, if necessary.
STABILIZATION
If anaphylaxis (circulatory collapse or airway compromise), consider epinephrine (1:1000) SC 0.3-0.5 q15min.
GENERAL MEASURES
• Symptomatic, supportive management
• Avoid known triggers.
• Cool, moist compresses to control itching or burning
MEDICATION (DRUGS)
First Line
• 1st generation antihistamines for acute angioedema
- Older children and adults: hydroxyzine (Vistaril 5 mg/5 cc, 25 tablets) 10-25 mg t.i.d. or diphenhydramine (Benadryl) 25-50 mg q6h
- Children under 6 years of age: Diphenhydramine 12.5 mg (elixir) q6-8h (5 mg/kg/day)
• 2nd generation H1 blockers are less sedating because they do not cross the blood-brain barrier.
- Fexofenadine (Allegra) 60 mg b.i.d.
- Loratadine (Claritin) 10 mg daily
- Acrivastine (Semprex) 8 mg t.i.d.
- Cetirizine (Zyrtec) 10 mg daily, which is more sedating than others in this class
• Anaphylaxis
- Intubation if airway is threatened
- Epinephrine 1:1,000, 0.2-0.3 mL IV or SQ
- Specific HAE and AAE therapy
- C1-INH concentrate
- Attenuated androgens: Danazol or stanozolol are particularly effective for prevention of HAE because they increase the amount of active C1-INH. Give 200-600 mg daily for 1 month, then 5 days on, 5 days off. The side effects are headaches, weight gain, and hematuria.
- Antifibrinolytic agents (plasmin inhibitors), such as tranexamic acid and aminocaproic acid, may also be used, but are not as effective as attenuated androgens in the management of HAE. On rare occasions they can cause thrombophlebitis, embolism, or myositis.
• Contraindications
- Danazol not to be used in childhood, pregnancy, lactation, and prostate cancer
• Precautions
- Drowsiness with 1st generation drugs
- Second generation H1 blockers should be used with caution in pregnancy and the elderly.
Second Line
Doxepin (Sinequan) may be effective for angioedema (10-25 mg at bedtime)
FOLLOW-UP
PROGNOSIS
Most patients with idiopathic angioedema do well. Chronic forms depend on underlying pathology.
COMPLICATIONS
• Anaphylaxis
• Respiratory compromise
PATIENT MONITORING
• Diagnostic work-up if symptoms are severe, persistent, or recurrent
• Protect airway if mouth, tongue, or throat is involved
REFERENCES
1. Bowen T, et al. Canadian 2003 international consensus algorithm for the diagnosis, therapy, and management of hereditary angioedema. J Allergy Clin Immunol. 2004;114(3):629-637.
2. Charlesworth EN. Differential diagnosis of angioedema. Allergy Asthma Proc. 2002;23:337-339.
3. Frigas E, Nzeako UC. Angioedema. Clin Rev Allerg Immunol. 2002;23:217-231.
4. Heymann WR. Acquired angioedema. J Am Acad Dermatol. 1997;26:611-615.
5. Kim JS, Pongracic JA. Hereditary and aquired angioedema. Allergy Asthma Proc. 2004;25:S47-S49.
6. Nzeako UC, Frigas E, Tremaine WJ. Hereditary angioedema: a broad review for clinicians. Arch Intern Med. 2001;161:2417-2429.
ANGINA
ANGINA - Philip P. Lobstein, MD
BASICS
DESCRIPTION
• Symptom complex resulting from mismatch of myocardial oxygen demand and supply:
- Classic angina: A sense of choking or of pressure or heaviness deep to the precordium, usually brought on by exertion or anxiety and relieved by rest
- Anginal equivalent: Exertional dyspnea or exertional fatigue, which results from myocardial ischemia and is relieved by rest or nitroglycerin
- Variant angina: Also referred to as Prinzmetal angina; describes angina occurring at rest in atypical patterns such as after exercise or nocturnally. Prinzmetal angina is caused by coronary artery spasm, and is associated with ECG changes (usually ST elevation) during symptoms
- Stable angina: Predictable chest discomfort that occurs in a consistent pattern at a certain level of exertion and is relieved with rest or nitroglycerin
- Unstable angina: Pain that is new or is changed in character to become more frequent, more severe, or both. Unstable angina portends myocardial infarction in a certain percentage of patients.
• System(s) Affected: Cardiovascular
• Synonym(s): Heberden syndrome
ALERT
Geriatric Considerations
Patients may be very sensitive to the side effects of the medications.
Pediatric Considerations
Suspect familial dyslipidemias in children presenting with manifestations of coronary artery disease.
Pregnancy Considerations
Other diagnoses should be excluded, and the patient managed closely by an obstetrician or family physician and cardiologist: The metabolic demands of pregnancy will exacerbate symptoms and directly interfere with treatment.
GENERAL PREVENTION
• Discontinue tobacco, adherence to low fat/low cholesterol diet, regular aerobic exercise program
• Antilipidemics if indicated by current ATP guidelines
• Daily aspirin in those without contraindications
EPIDEMIOLOGY
• Predominant age: Most common in middle age and older men; postmenopausal women
• Predominant sex: Male > Female (before menopause)
Incidence
Presenting symptom of coronary artery
• Male: 38%
• Female: 61%
RISK FACTORS
• Family history of premature coronary artery disease (CAD)
• Hypercholesterolemia
• Hypertension
• Tobacco abuse
• Diabetes mellitus
• Male gender
• Advanced age
• Morbid obesity
• Hyperhomocysteinemia (possibly)
Genetics
Coronary artery disease has genetic implications.
ETIOLOGY
• Atherosclerosis of the coronary arteries
• Coronary artery spasm
• Aortic stenosis
• Hypertrophic cardiomyopathy
• Severe hypertension
• Aortic insufficiency
• Primary pulmonary hypertension
ASSOCIATED CONDITIONS
• Hypercholesterolemia
• Claudication, Peripheral vascular disease
• Arterial aneurysms
• Mitral regurgitation
• Papillary muscle dysfunction
• Ventricular aneurysm
• Abdominal aortic aneurysm
• Hypertrophic subaortic stenosis
• Primary hyperthyroidism
• Pernicious anemia and other high output states
DIAGNOSIS
SIGNS AND SYMPTOMS
• Precordial pressure or heaviness, radiating to the back, neck, or arms; brought on by exertion, emotional stress, meals, cold air, or smoking; and relieved by rest or nitrates
• Discomfort may radiate to the neck, lower jaw, teeth, shoulders, and inner aspects of the arms or back.
• Discomfort may be described with a clenched fist over the sternum (Levine sign).
• Dyspnea on exertion may present as the only symptom.
• A choking sensation on exertion is a classic symptom.
• Atypical symptoms are more likely in women, elderly, and diabetic patients.
History
• Quality of any previous anginal episodes and pattern over time
• Underlying history of heart disease or valvular disease
• Family history of MI, CAD, sudden death
Physical Exam
May see signs of dyslipidemia (xanthomas, xanthelasma, diminished peripheral pulses, carotid bruits).
TESTS
• ECG
- May show evidence of ischemia or prior myocardial infarction; follow-up testing via angiography is warranted. Other findings are nonspecific and tracings are frequently normal.
- Bundle branch block, Wolff-Parkinson-White syndrome, or intraventricular conduction delay may make the ECG unreliable.
• If normal ECG, exercise stress treadmill testing (ETT) based on probability is indicated.
- ETT with imaging-via echocardiography or perfusion imaging with sestamibi.
- In patients who cannot tolerate exercise, pharmacologic stress testing should be performed
- Women have lower sensitivity and specificity with ETT than do men; exercise echocardiography is indicated
- In Men
Low probability: ETT without imaging
Intermediate probability: ETT with imaging
High probability: ETT prior to angiography
Lab
• Total cholesterol: Frequently elevated
• HDL cholesterol: Frequently reduced
• LDL cholesterol: Frequently elevated
• CRP: Only useful (and offers no better predictive value than standard CHD risk factors) in those with Intermediate to high risk; should be measured at least twice over 2 weeks; is not predictive in low risk patients and in those on a -blocker or statin.
Imaging
• Radionuclide scintigraphy
• Stress echocardiography
• Stress scintigraphy
• Coronary angiography
Diagnostic Procedures/Surgery
• Definitive evaluation requires coronary arteriography for confirmation and delineation of coronary disease, and direction of interventional therapy or surgery. Coronary artery stenting has proven very effective, with restenosis rates (in skilled hands) often 10%, eliminating need for surgery in many cases.
• Surgery in CAD not amenable to angioplasty, and stenting has proven to have a long-term benefit.
Pathological Findings
Atherosclerosis of the coronary arteries
DIFFERENTIAL DIAGNOSIS
• Esophagitis (GERD)
• Esophageal spasm
• Peptic ulcer disease
• Gastritis or nonulcer dyspepsia
• Cholecystitis
• Costochondritis
• Pericarditis
• Aortic dissection
• Pleurisy
• Pulmonary embolus
• Pulmonary hypertension
• Pneumothorax
• Radiculopathy
• Shoulder arthropathy
• Psychological: Anxiety and panic disorders
TREATMENT
PRE-HOSPITAL
• EMS activation if chest discomfort unimproved or worsening 5 minutes after 1 nitroglycerin dose (1)[C]
- EMS to initiate IV, O2, and monitor
- Aspirin administration if ACS suspected and not previously taken or contraindicated
GENERAL MEASURES
• The patient's symptoms should be brought under control medically. If symptoms are unstable, hospitalization is warranted.
• Treatment goal involves reducing myocardial oxygen demand or to increase oxygen supply.
• Noninvasive testing often is indicated as a means of stratifying the patient's risk for an event that might seriously compromise myocardial function.
• Quit smoking.
• Minimize emotional stress.
• Weight reduction in obese patients (2)[C]
Diet
Low-fat, low-cholesterol, low-salt diet
Activity
• As tolerated after consulting physician
• Exercise program after physician's approval; very effective if consistent
SPECIAL THERAPY
Complementary and Alternative Medicine
Relaxation/stress reduction therapy may help reduce anginal aggravations.
MEDICATION (DRUGS)
First Line
• Aspirin: 81-325 mg/d
• -Blockers are effective in reducing heart rate and thereby decreasing oxygen consumption and reducing angina
- Atenolol 25-100 mg/d, metoprolol 25-100 mg b.i.d., or bisoprolol 2.5-10/d
- Adjust doses according to clinical response. Aim to maintain resting heart rate of 50-60 beats per minute.
- Side effects are infrequent but include fatigue, exercise intolerance, erectile dysfunction, and exacerbation of peripheral vascular and obstructive pulmonary disease.
• Nitroglycerin 0.4 mg SL is the most effective therapy for acute anginal episodes
- May repeat 2-3 times over a 10-15 minute period; if no relief, the patient should seek immediate medical attention.
• Long-acting nitrates (mononitrates or transdermal nitrates)
- Should be used with a drug-free interval of 10-14 hours to prevent tolerance
- Tachyphylaxis occurs rapidly.
- Preload reduction and coronary vasodilatation
- Side effects: Headaches and hypotension, tend to clear with continued usage.
- A -blocker or calcium channel blocker should be used in conjunction with the nitrates during the drug-free interval.
- Caution patients not to use in conjunction with oral medicine for erectile dysfunction, such as sildenafil (Viagra).
• Long-acting calcium channel blockers: Verapamil 160-480 mg/d or diltiazem 90-360 mg/d, or nifedipine 30-120 mg/d, or amlodipine 5-20 mg/d. Drug of choice for variant angina. The various agents have their own individual side effects (i.e., verapamil, constipation; nifedipine, peripheral edema).
• HMG CoA reductase inhibitors (e.g., atorvastatin, pravastatin, lovastatin) for hypercholesterolemia: These drugs decrease incidence of symptomatic CAD and reduce both myocardial infarction and death from MI. LDL target levels below 100 mg/dL in diabetes mellitus and 130 mg/dL in low- to moderate-risk patients.
• ACE inhibitors (ramipril 10 mg) in patients with CAD or other vascular disease (3)[B], and particularly those with diabetes or left ventricular (LV) systolic dysfunction (3)[A] have been shown to reduce both cardiovascular death and MI.
• Heparin: Low-molecular-weight heparin should be initiated in patients hospitalized with unstable angina.
• Glycoprotein IIb/IIIa receptor antagonists (Integrilin): Indicated in certain patients hospitalized with unstable angina
• Combination therapy may be used (especially nitrates plus calcium antagonists with or without -blockers).
• Contraindications:
- Sildenafil (Viagra), vardenafil (Levitra), or tadalafil (Cialis) with nitrates should be avoided due to the risk of hypotension and possible death.
• Precautions: Avoid verapamil and diltiazem with compromised ventricular function (LV ejection fraction 40%) especially in conjunction with -blockers.
• Significant possible interactions:
- Combination therapies may impair LV function and precipitate heart failure.
- -Blockers and calcium channel blocker: May combine to produce symptomatic heart block, although either class of drug may act alone in producing this side effect
- Niacin may worsen glucose intolerance.
Second Line
• Current ATP guidelines support the use of lipid-lowering drugs in patients with unfavorable lipid profiles and suspected or documented CAD with or without symptoms (4)[A].
• Consider adding clopidogrel (Plavix) to ASA for severe diffuse CAD. The use of Plavix is indicated after stent placement for at least 9 months to significantly reduce restenosis rates.
SURGERY
Coronary artery bypass graft surgery, angioplasty, stent placement, atherectomy in selected cases
FOLLOW-UP
DISPOSITION
Admission Criteria
Unstable symptoms warrant hospitalization for evaluation.
PROGNOSIS
• Variable; depends on the extent of CAD as well as LV function
• Annual mortality is 3-4% overall
COMPLICATIONS
• Related to myocardial damage occurring during infarction
• Arrhythmia
• Cardiac arrest
• Congestive heart failure
PATIENT MONITORING
• Depends on the frequency and severity of the complaints
• Hospitalization is indicated in patients diagnosed with unstable angina.
REFERENCES
1. Antman EM, Ane DT, Armstrong PW, et al. Guidelines for the management of patients with ST-elevation myocardial infarctionexecutive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2004;110:588-636.
2. Gibbons RJ, Abrams J, Chatterjee K, et al. ACC/AHA 2002 guideline update for the management of patients with chronic stable anginasummary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2003;107:149-158.
3. Yusuf S, Sleight P, Pogue J, et al. Effects of an angiotensin-converting-enzyme inhibitor ramipril on cardiovascular events in high-risk patients. The HOPE Study Investigators. N Engl J Med. 2000;342:145-153.
4. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497.
ANEURYSM OF THE ABDOMINAL AORTA
ANEURYSM OF THE ABDOMINAL AORTA - David H. Stubbs, MD
BASICS
DESCRIPTION
A permanent localized (i.e., focal) dilatation of the abdominal aorta having at least a 50% increase in diameter compared to the expected diameter of the artery. The clinical presentation of aneurysms relates to location, size, type, and comorbid factors affecting the patient. The majority of aneurysms are asymptomatic. Some present with rupture, others with embolism or thrombosis. The management and indications for surgical repair is dictated by the natural history of the aneurysm, the type, the consequences of repair, and the general status of the patient. There are two types, which are infrarenal (90%) and thoracoabdominal.
• System(s) Affected: Cardiovascular; Hemic/ Lymphatic/Immunologic
• Synonym(s): Aortic aneurysms; AAA
ALERT
Geriatric Considerations
Familial aggregations exist, but pathogenesis relates to interaction of genetic, environmental, and biochemical factors.
- Marfan syndrome
- Ehlers-Danlos syndrome
Pediatric Considerations
Etiology more likely infectious or collagen disorders
GENERAL PREVENTION
Screening: 1-time ultrasound screening for AAA in male patients, ages 65-75 who have ever smoked >100 cigarettes
EPIDEMIOLOGY
• Predominant age: Elderly
• Predominant sex: Male > Female (4:1)
Incidence
• >15,000 deaths per year
• 10th leading cause of death in males >55
- In men >60 years: 2-5%
- In men >65 years: 6%
- In men >75 years: 11%
• In women >65 years: 4%
• High risk groups
- Coronary disease: 5-9%
- Peripheral vascular disease: 10-15%
- 1st degree relative with AAA: 25%
- Males = 40% risk
- Females = 15% risk
- Obese patients >65 years
- Presence of peripheral aneurysms
RISK FACTORS
• Hypertension
• Nicotine
• COPD
• Familial: Siblings of patients with AAA
ETIOLOGY
• Atherosclerosis
• Inflammatory (5-10%)
• Traumatic
• Genetic predisposition (Marfan, Ehlers-Danlos)
ASSOCIATED CONDITIONS
• Marfan syndrome
• Ehlers-Danlos syndrome
DIAGNOSIS
SIGNS AND SYMPTOMS
Physical Exam
Majority of patients with abdominal aortic aneurysm (AAA) are asymptomatic. Many are discovered during radiologic procedures performed for other reasons.
• Pulsatile epigastric mass
• Vague abdominal pain
- May radiate to the back of flank
• Encroachment by aneurysm
- Vertebral body erosion
- Gastric outlet obstruction
- Ureteral obstruction
• Lower extremity ischemia secondary to microembolization or macroembolization of mural thrombus
• The triad of shock, pulsatile mass, and abdominal pain should always suggest rupture of AAA
- Shock may be absent if the rupture is contained.
- Palpable pulsatile mass may be absent in up to 50% of the patients with rupture.
- Pain may radiate to the back or into the groin.
- Rupture associated with 90% mortality rate.
• Unusual presentations
- Primary aortoenteric fistula: Erosion/rupture of AAA into duodenum
- Aortocaval fistula: Erosion/rupture of AAA into vena cava or left renal vein
- Inflammatory aneurysm: Encasement of aneurysm by thick inflammatory rind associated with chronic abdominal pain, weight loss, and elevated ESR
- Surrounding viscera are densely adherent.
ALERT
Geriatric Considerations
More common in this age group and may present atypically
TESTS
Lab
Evaluation for concomitant CAD
• Selective evaluation for CAD is appropriate prior to elective AAA repair (i.e., cardiac clearance).
• Patients with mild, stable cardiac symptoms should have a noninvasive cardiac stress study.
• Coronary revascularization should be performed when the CAD would merit intervention on its own.
Imaging
Screening: 1-time ultrasound screening for AAA in male patients, ages 65-75, who have ever smoked >100 cigarettes
Diagnostic Procedures/Surgery
• Clinical examination
• Ultrasonography is the preferred initial diagnostic tool in suspected AAA, but is not reliable for a diagnosis of a rupture.
• CT scans are the preferred preoperative study. Avoid contrast if the patient has significant renal insufficiency. CT scans assist in the diagnosis of an inflammatory aneurysm.
• MRI: Similar to CT and avoids contrast. MR angiography may replace arteriograms.
• Aortography: Does not define outside dimensions of aneurysms.
• Indications for aortography
- Associated renovascular hypertension
- Symptoms of visceral angina
- Significant iliofemoral occlusive disease
- Peripheral aneurysms
- Horseshoe or pelvic kidney
- Prior colectomy
DIFFERENTIAL DIAGNOSIS
• Abdominal masses transmitting aortic pulse
• Other causes of abdominal pain (e.g., peptic ulcer disease)
• Other causes of back pain (e.g., arthritis, metastatic disease)
TREATMENT
STABILIZATION
• The treatment of AAA is elective repair.
• The prevention of AAA is elective repair.
GENERAL MEASURES
• Control hypertension
• Treat atherosclerotic risk factors
• Stop smoking
SURGERY
• Repair when
- Rupture occurs
- Size >5.5 cm (or >6 cm in poor surgical risk patients)
- Expansion >0.5 cm/6 months
- Symptoms occur
• Poor surgical risk patients
- Class III-IV angina; LVEF 30%; recent CHF or MI; severe valve disease
- Serum creatinine >3 mg/dL
- PaO2 50 mm Hg; FEV1IL
- Cirrhosis with ascites
- Diffuse retroperitoneal fibrosis; hostile abdomen
- Physiologic age > chronological age
• Endovascular aneurysm repair
- There are currently 3 devices approved by the FDA for marketing. Late complications of these devices continue to occur.
- Long-term CT surveillance is required.
- Adequate iliac/femoral access
- Infrarenal non-aneurysmal neck length of at least 1 cm at the proximal and distal ends of the aneurysm
- Morphology suitable for endovascular repair
- One of the following: A diameter >5 cm, a diameter of 4-5 cm, and an increase in size by 0.5 cm in the past 6 months.
- Health status adequate to undergo the 2-hour plus implementation procedure
FOLLOW-UP
PROGNOSIS
• Aneurysms usually expand over time (Laplace's Law: T (wall tension) = Pressure Radius. Wall tension is directly related to blood pressure and the radius of the artery.) When wall tension exceeds wall tensile strength, rupture occurs.
• Surgical Outcomes:Morbidity 32%; cardiac (MI) 11%; mortality 4.2%
• Risk of morbidity and mortality increase with age
• Operative mortality is inverse to surgeon volume, hospital volume, specialty (vascular vs general surgeon)
• Non-repair (natural history of AAA >5.5 cm); 57% mortality within 1.5 years
• Mean expansion is 0.4 cm per year
• Rupture risk is increased by:
- Diastolic hypertension
- Tobacco use
- Diameter >6 cm
- COPD
- Familial history
• Ruptured aneurysms
- 8% die before receiving definitive care and 50% of the remaining die during their treatment or hospitalization.
COMPLICATIONS
• Rupture
• Associated dissection
• Thrombosis
• Embolization distally
PATIENT MONITORING
• Hypertension control
• Lipid control
• Recurrent assessment of smoking status
• Perioperative complications
- MI: 5%
- Renal failure: 6%, chronic dialysis: 1%
- Pulmonary failure: 5-8%
- Microembolism (trash foot): 1-4%
- Ischemic colitis: 0.5-1%
- Wound infection: 2%
- Graft infection: 0.5%
- Stroke: 0.5-1%
- Paraplegia: 0.2%
• Postsurgical monitoring
- Anastomotic aneurysm
- Graft infections
- Aortoenteric fistula
- Graft limb occlusion
- Additional aneurysms: Thoracic, thoracoabdominal, femoral
REFERENCES
1. Irvin TT. Abdominal pain: A surgical audit of 1190 emergency admissions. Br J Surg. 1989;76:1121.
2. Johnston W, Rutherford RB, Tilson MD, et al. Suggested standards for reporting on arterial aneurysms. J Vasc Surg. 1991;13:452.
3. Lederle FA, Wilson SE, Johnson GR, et al. Aneurysm detection and management Veterans Affairs cooperative study group. Immediate repair compared with surveillance of small abdominal aortic aneurysms. N Engl J Med. 2002;346:1437-1444.
4. Mason JJ, Owens DK, Harris RA, Cooke JP, Hlatky MA. The role of coronary angiography and coronary revascularization before non-cardiac vascular surgery. JAMA. 1995;273:1919.
5. Porter JM, ed. The Year Book of Vascular Surgery. New York, NY: Mosby-Year Book; 1997.
6. Rutherford B, ed. Vascular Surgery. 14th ed. Philadelphia: WB Saunders; 1995.
7. Szilagyi DE, Smith RF, DeRusso FJ, Elliott JP, Sherrin FW. Contribution of abdominal aortic aneurysmectomy to prolongation of life. Ann Surg. 1966;164:678.
ANEMIA, SIDEROBLASTIC
ANEMIA, SIDEROBLASTIC - Anne C. Nofziger, MD
BASICS
DESCRIPTION
A heterogeneous group of disorders characterized by microcytic, hypochromic anemia, impaired heme biosynthesis causing ineffective erythropoiesis, and ringed sideroblasts in the bone marrow. Severity and course may range from severe progressive to indolent asymptomatic anemia; onset may be congenital or late in life.
GENERAL PREVENTION
Pyridoxine prophylaxis with INH therapy
EPIDEMIOLOGY
• As a group, sideroblastic anemias (SA) are uncommon, and specific incidence/prevalence information is difficult to find.
• Acquired forms more common than hereditary forms (1), usually occur in older adults; present in 25-30% of alcoholics with anemia (2)
• Several hundred X-linked cases described (3) Hereditary forms variably severe, usually manifest in childhood
RISK FACTORS
• Male gender (X-linked SA)
• Family history of hereditary SA
• Chronic alcohol abuse
• Gastric bypass surgery (1 case report) (4)
Genetics
• Usually X-linked
- Defect in aminolevulinic acid synthase (ALAS-2 mutation), the first and rate-limiting enzyme in heme biosynthesis
- With congenital ataxia: hABC7 gene mutations (mitochondrial transport protein)
• Rarely autosomal dominant or recessive; gene(s) unknown
• Mitochondrial cytopathy
- Heterogeneous, involve deletions in mtDNA
- Unpredictable maternal inheritance
• See "Etiology"
PATHOPHYSIOLOGY
• Impaired heme biosynthesis within mitochondria
• Ineffective erythropoiesis
• Increased GI absorption of iron (Fe overload)
• Enhanced apoptosis in bone marrow
• Possibly, reactive oxygen species play a role
ETIOLOGY
Acquired SA
• Reversible
• Drugs and toxins
- Ethanol (SA is a later finding in multifactorial anemia related to alcoholism)
- INH
- Chloramphenicol
- Cycloserine
- Zinc toxicity (Cu deficiency)
• Nutritional deficiencies
- Pyridoxine deficiency
- Copper deficiency
Post-gastrectomy
Prolonged parenteral nutrition
Prolonged zinc supplementation
• Hypothermia
• Acquired idiopathic sideroblastic anemia (AISA)
- Pure sideroblastic anemia (PSA)
Only the erythroid line affected
- Refractory anemia with ringed sideroblasts (RARS)
Myelodysplasia, other cell lines also affected
- Associated with hematologic malignancies, myeloproliferative disorders
Hereditary SA
• X-linked
• Autosomal dominant, recessive, maternal inheritance
• Mitochondrial cytopathy
- Wolfram syndrome
- Pearson syndrome
Congenital SA
Disproportionately male, sporadic, mild to severe, kindreds too small to analyze inheritance
ASSOCIATED CONDITIONS
• Alcoholism
• According to mutation, e.g., severe congenital ataxia (hABC7 mutation), pancreatic dysfunction (Pearson syndrome)
• Iron overload or "erythropoeitic hemochromatosis" (2) develops over time in all but reversible and x-linked/ataxia forms.
• Rarely, coexisting iron deficiency masks SA.
DIAGNOSIS
PRE HOSPITAL
Often an incidental finding
SIGNS AND SYMPTOMS
• Moderate to severe anemia
- Fatigue
- Dizziness
- Diminished exercise tolerance
- More symptomatic in older patients with comorbid conditions
• Specific to cause
- Pyridoxine deficiency (peripheral neuropathy, dermatitis)
- Alcoholism
• Manifestations of iron overload
History
• Toxin or drug exposures
• Family history of anemia, especially in men
Physical Exam
• No pathognomonic physical findings
• Mild-moderate hepatosplenomegaly at diagnosis in 1/3-1/2 of patients with AISA (2)
TESTS
Lab
• CBC
- Low MCH
- Low MCHC
- Low MCV (may be normal or high, esp. in myelodysplasia)
- High RDW
- Hgb highly variable
- Siderocytes in peripheral smear (occasional)
- WBC normal; may be reduced if hypersplenism, myelodysplasia
- Platelets normal; may be reduced if hypersplenism, myelodysplasia
- Low reticulocyte count
• Iron studies
- Ferritin increased
- Transferrin saturation increased
- Serum transferrin decreased
- Reticuloendothelial iron increased
• Serum copper, ceruloplasmin, serum zinc if suspected as cause
• Liver enzyme derangements possible depending on cause (EtOH, cirrhosis, Fe overload)
• Molecular studies identify specific mutations causing hereditary SA syndromes
• Myelodysplasia: Morphologic and cytogenetic evaluation required for prognosis
Diagnostic Procedures/Surgery
• Bone marrow examination confirms diagnosis of SA
• Liver biopsy is best; test to assess degree of iron overload.
• See "Pathological Findings"
Pathological Findings
• Bone marrow examination is the key diagnostic modality (1)[C]
- Normoblastic erythroid hyperplasia
- Perls' Prussian blue iron stain: Ringed sideroblasts, >10% of erythroblasts with increased number of abnormally large granules ringing the nucleus
- Electron microscopy: Iron-overloaded mitochondria within erythroblasts
- Iron-laden macrophages
• Liver biopsy
- Iron deposition as in hereditary hemachromatosis
- Micronodular cirrhosis by 3rd or 4th decade
DIFFERENTIAL DIAGNOSIS
• Thalassemias
• Iron deficiency anemia
• Anemia of chronic disease
• Myelodysplastic syndromes
• Lead toxicity with anemia
TREATMENT
GENERAL MEASURES
Treatment is largely supportive
• Pyridoxine supplementation improves symptoms in responsive cases (1)[B]
• Eliminate toxins, causative drugs
• Periodic transfusion: Maintain acceptable hemoglobin to alleviate symptoms and allow normal growth and development (children) (1)[B]
• Prevent end-organ damage from severe iron overload (1)[B]
- Phlebotomy preferred modality if anemia is mild or moderate
- Iron chelation in patients with more severe anemia, or requiring more transfusions
Diet
Address relevant nutritional deficiencies
Activity
As tolerated
SPECIAL THERAPY
Allogeneic stem cell transplantation has been successful in a few cases in younger patients with myelodysplastic syndromes.
IV Fluids
RBC transfusion when necessary
MEDICATION (DRUGS)
First Line
• Trial of pyridoxine is indicated because it has few drawbacks and is very beneficial in responsive cases (1)[B]
- Pyridoxine 50-100 mg PO daily
- Maintenance: Minimum dose to maintain acceptable hgb.
- Supplement folate to compensate for increased erythropoiesis if effective
- Response likely if SA caused by alcohol abuse, pyridoxine antagonists, or some forms of hereditary x-linked SA.
• Chelation therapy for iron overload (1)[B]
• Deferoxamine 40 mg/kg/d in continuous 12-24-hour daily infusions
- Limit ascorbate intake to 200 mg/d
- Auditory/visual toxicity very rare
• Defirasirox is a new oral once-daily iron chelator
- No long-term safety data
- Main complications skin rash, GI upset
• Goal of therapy is to maintain serum ferritin 500 ug/L
Second Line
• Myelodysplasia: PSA and RARS
• Treatment considerations as above, though no expected response to pyridoxine
• Some respond to combination of erythropoeitin (EPO) and granulocyte colony-stimulating factor (G-CSF) (1)[C]
• Chemotherapeutic agents may have a role.
SURGERY
• Splenectomy is contraindicated due to frequent postoperative thromboembolic complications (2)[B].
FOLLOW-UP
DISPOSITION
Admission Criteria
Generally managed in outpatient settings except for treatment of complications such as CHF, dysrhythmias.
Issues for Referral
• Hematology consultation is helpful for diagnosis and management, particularly if no reversible cause identified.
• Genetic counseling is important for patients with heritable cause of SA.
PROGNOSIS
• 75% of x-linked SA with ALAS-2 mutations are pyridoxine responsive (2)
• Prognosis better if iron overload prevented
• Aquired Idiopathic SA:
- RARS: 1- and 5-year cumulative risk of acute leukemia are 20% and 38%, respectively (1)
- When only the erythroid line is affected (PSA), course as in age-matched controls, transformation to leukemia not observed. (2)
- If SA follows treatment for malignancy, leukemic transformation is common.
COMPLICATIONS
• Iron overload causing organ damage
- Cardiac arrhythmia or CHF
- Hepatic dysfunction
• Transfusion complications
PATIENT MONITORING
• Yearly ferritin and transferrin saturation to monitor for Fe overload
• Follow response to treatment: Reticulocytosis within 2 weeks, improved hgb within 1-2 months of response to pyridoxine, and correction of nutritional deficiency or withdrawal of reversible cause.
REFERENCES
1. Alcindor T, Bridges KR. Sideroblastic anaemias. Br J Haematol. 2002;116:733-743.
2. Bottomley SS. Sideroblastic anemias. In: Greer JP, Foerster J, Lukens J, et al., eds. Wintrobe's Clinical Hematology, 11th ed. Philadelphia: Lippincott, Williams and Wilkins; 2004.
3. http://ghr.nlm.nih.gov/ghr/ accessed February 2006
4. Almhanna K, Khan P, Schaldenbrand M, Momin F. Sideroblastic anemia after bariatric surgery. Am J Hematol. 2006;81(2):155-156.
ADDITIONAL READING
• See http://www.genetests.org for counseling information on specific heritable SA syndromes and availability of testing.
• http://ghr.nlm.nih.gov/condition=xlinkedsideroblasticanemia
ANEMIA, SICKLE CELL
ANEMIA, SICKLE CELL - Diane M. Haleem, PhD, RN
BASICS
DESCRIPTION
• A chronic hemoglobinopathy transmitted genetically; marked by moderately severe chronic hemolytic anemia, periodic acute episodes of painful "crises," and increased susceptibility to intercurrent infections, especially Saccharomyces pneumoniae.
• The heterozygous condition (Hb A/S) is called sickle cell trait and is usually asymptomatic with no anemia.
• System(s) Affected: Hematologic, Lymphatic/immunologic; Musculoskeletal
• Synonym(s): Sickle cell disease; Hb S disease
ALERT
Pediatric Considerations
• Sequestration crises and hand-foot syndrome seen only in infants/young children
• Functional asplenia in later childhood
• Adolescence/young adulthood
- Frequency of complications and organ/tissue damage increase with age (except for strokes, which occur mostly in childhood).
- Psychological complications: Body-image and sexual identity problems, interrupted schooling, career, restriction of activities, stigma of disease, low self-esteem
• Consider periodic transcranial Doppler ultrasound in all children ages 2-16
Pregnancy Considerations
• Usually complicated and hazardous, especially 3rd trimester and delivery
• Increased risk of crises, toxemia, infection, pulmonary infarction, phlebitis
• Fetal mortality 35-40%
• Partial exchange transfusion in 3rd trimester reduces maternal morbidity and fetal mortality.
• Chronic transfusions have been effective in diminishing episodes in pregnant women.
GENERAL PREVENTION
• Avoid conditions that precipitate sickling (hypoxia, dehydration, cold, infection, fever, acidosis, anesthesia).
• Granulocyte colony-stimulating factor is absolutely contraindicated.
EPIDEMIOLOGY
• Predominant age: All ages
• Predominant sex: Male = Female
Incidence
• ~1/500 African Americans and 1/1,000 Hispanics have sickle cell anemia.
• 10% African Americans have sickle trait.
• To a lesser extent, people from the Middle East, Mediterranean area, and aboriginal tribes in India
RISK FACTORS
• Vaso-occlusive crisis
- Hypoxia
- Dehydration, fever
- Infection
- Acidosis, cold
- Anesthesia
- Strenuous physical exercise
- Smoking
• Aplastic crisis
- Severe infections
- Human parvovirus B19 infection
- Folic acid deficiency
• Hyperhemolytic crisis
- Acute bacterial infections
- Exposure to oxidant drugs
Genetics
• Autosomal recessive, mostly in African Americans.
• Homozygous presence of a variant hemoglobin, Hb S, or sickle hemoglobin
• Heterozygous condition Hb A/S
ETIOLOGY
• At molecular level: Hb S is produced by substitution of valine for glutamic acid in the 6th amino acid position of the -chains of the hemoglobin molecule. When deoxygenated, Hb S polymerizes and forms long rods that change RBC from biconcave to sickle shape.
• At cellular level: Sickle RBCs are inflexible; their odd shape and cell rigidity cause increased blood viscosity, stasis, mechanical obstruction of small arterioles and capillaries, and ischemia. Sickle RBCs are fragile, leading to hemolysis.
• At clinical level: Chronic anemia; "crises";
- Vaso-occlusive crisis ("painful crisis"): Most common; pain results from tissue necrosis secondary to vascular occlusion and tissue hypoxia. Progressive organ failure and acute tissue damage result from repeated vaso-occlusive episodes.
- Aplastic crisis: Suppression of RBC production by severe infection
- Hyperhemolytic crisis: Accelerated hemolysis; increased RBC fragility/shortened lifespan
- Sequestration crisis: Splenic sequestration of blood (only in infants/young children)
- Susceptibility to infection: Impaired/absent splenic function; defect in the alternate pathway of complement activation
ASSOCIATED CONDITIONS
The psychosocial effects can result in low self-esteem, depression, and dependency.
DIAGNOSIS
SIGNS AND SYMPTOMS
History
• Chronic hemolytic anemia
• Mild scleral icterus
• Increased infection risk, i.e., pneumococcal sepsis and Salmonella osteomyelitis
• Functional asplenia by ~5-6 years of age
• Delayed physical/sexual maturation
Physical Exam
• After 6 months of age, earliest symptoms are pallor and symmetric, painful swelling of the hands and feet (hand-foot syndrome).
• Often asymptomatic in early months of life
• Painful "crises" in bones, joints, abdomen, back, and viscera (90% of all hospital admissions)
• Acute chest syndrome SS tachycardia, fever, bilateral infiltrates caused by decrease in hemoglobin and infarction of pulmonary vasculature (clinical picture consistent with pneumonia and/or infection)
• Many multisystem complications, especially in later childhood and adolescence
TESTS
Lab
• Hb electrophoresis
• Sickle cell anemia (FS pattern): 80-100% Hb S, variable amounts of Hb F and no Hb A. Sickle cell trait (FS pattern): 20-40% Hb S, 60-80% Hb A1, minimal Hb F.
• Screening tests: Sodium metabisulfite reduction test; "Sickledex" test
• Hemoglobin approximately 8 g/dL (1.24 mmol/L); RBC indices usually normal, but mean corpuscular volume (MCV) >75 m3 (>75 fL)
• Reticulocytosis of 10-20%
• Leukocytosis; bands in absence of infection
• Thrombocytosis
• Peripheral smear: Sickled RBCs, nucleated RBCs, Howell-Jolly bodies
• Serum bilirubin mildly elevated (2-4 mg/dL [34-68 mol/L]); fecal/urinary urobilinogen high
• ESR low
• Serum LDH elevated
• Haptoglobin absent or very low
• Disorders that may alter lab results: Infection
Imaging
• Bone scan (to rule out osteomyelitis)
• CT/MRI (to rule out CVA)
• Chest radiograph: May show enlarged heart; diffuse alveolar infiltrates in acute chest syndrome
• Transcranial Doppler: Start at age 2; repeat yearly (1,2,3)[B]
• Echocardiography to detect pulmonary hypertension (2,3)[C]
Pathological Findings
• In moderate to severe cases, hyposplenism due to autosplenectomy is common.
• Hypoxia/infarction in multiple organs
DIFFERENTIAL DIAGNOSIS
• Anemia: Other hemoglobinopathies (e.g., Hb SC disease, Hb C disease, sickle cell- thalassemia)
• Painful crises: Other causes of acute pain in bones, joints, and abdomen
TREATMENT
STABILIZATION
General health maintenance: Assessment of growth/development, regular immunizations, vision/hearing screening, and dental care
GENERAL MEASURES
• Infections/fever: Treatment with antibiotics
• Minimize factors that enhance sickling
• Painful crises: Hydration (2X maintenance fluids); analgesics; oxygen if hypoxic
• Transfusion needed with aplastic crises, severe complications (i.e., CVA), before surgery
• Retinal evaluation starting at school age to detect proliferative sickle retinopathy
• Occupational therapy
• Cognitive and behavioral intervention: Include distraction, relaxation, and motivational therapy
• Support groups
• Special immunizations (1,3)[B]
- Influenza vaccine yearly starting at age 2
- Heptavalent conjugated pneumococcal vaccine at 2, 4, 6 months; booster at 15 months, 2 years, 5 years
- 23-valent pneumococcal vaccine at 2 years; booster at age 5; always separate this by 8 weeks from heptavalent vaccine
- Meningococcal vaccine after age 2
Diet
• Folic acid supplementation
• Avoid alcohol (leads to dehydration)
Activity
Bed rest with crises
Physical Therapy
To include heat, massage, and exercise
IV Fluids
2X maintenance fluids (NS preferred) for severe painful crises (2)[C]
MEDICATION (DRUGS)
First Line
• Supplemental oxygen
• Painful crises (mild, outpatient)
- Nonnarcotic analgesics (ibuprofen, tramadol) (1,2,3)[C]
• Painful crises (severe, hospitalized) (1,2,3)[B]
- Parenteral narcotics (e.g., morphine on fixed schedule); (PCA pump may be useful.)
- Corticosteroids (dexamethasone 0.3 mg/kg q12h for 4 doses in children) may be used for painful crisis or chest syndrome.
• Prevention of painful crisis
- Hydroxyurea (increases hemoglobin F levels thus decreasing permanent formation of sickle cells.) in adult patients with 3 crisis/year. Start with 15 mg/kg/d single daily dose; titrate upward every 12 weeks if blood counts satisfactory. Increase in 5 mg/kg increments to maximum of 35 mg/kg/d. Reduces crisis and chest syndrome 50%; long-term safety unknown. Contraindicated in pregnancy (2-4)[A].
- Inhaled nitric oxide, arginine butyrate (has anti-sticking properties; may enhance availability of nitric oxide) and combination of erythropoietin with hydroxyurea (2,4)[B].
• For infections prior to culture results (2,3)[C], prescribe an antibiotic that covers S. pneumoniae, H. influenzae, mycoplasma pneumoniae, and Chlamydia pneumoniae. If osteomyelitis, cover for Staphylococcus aureus and Salmonella.
• Prophylactic penicillin is indicated in all infants and children starting at 2 months (1,4)[A].
- For 2-6 months of age: 62.5 mg b.i.d.
- For 6 months-3 years: 125 mg b.i.d.
- For 3-5 years: 250 mg b.i.d.
- If no pneumococcal infections and no splenectomy stop at 6 years; if high risk remains, continue until puberty.
- Alternative penicillin, benzathine IM 300,000 U/mo, ages 4 months-3 years, then 600,000 U/mo for 3-5 years
- Rising pneumococcal resistance to penicillin may change future recommendations.
• Precautions: Avoid high-dose estrogen oral contraceptives; consider Depo-Provera.
Second Line
• Other NSAIDs
• Folic acid supplements (1,3)[C]
- From 0-6 months: 0.1 mg/d
- From 6-12 months: 0.25 mg/d
- From 1-2 years: 0.5 mg/d
- Beyond age 2: 1 mg/d
SURGERY
Bone marrow transplantation is curative, but the availability is limited.
FOLLOW-UP
DISPOSITION
Admission Criteria
Severe pain, suspected infection or sepsis
PROGNOSIS
• Anemia is lifelong. In 2nd decade of life, patient usually experiences fewer crises, but complications are more frequent. Median age of death is 42 for men and 48 for women. Common causes are infections, thrombosis, pulmonary emboli, pulmonary hypertension, and renal failure.
• Children become anemic at infancy and begin to have sickle cell crisis at 1-2 years of age; some children die in their 1st year.
COMPLICATIONS
• Alloimmunization
• Bone infarct
• Aseptic necrosis of femoral head
• Cerebrovascular accidents (peak age 6-7)
- In the 10% of patients who suffer these, transfusions q3-4 weeks will reduce the risk by 90%. Initiate based on abnormal transcranial Doppler. May require iron chelation therapy.
• Cardiac enlargement
• Pulmonary hypertension
• Cholelithiasis/abnormal liver function
• Chronic leg ulcers
• Poor wound healing
• Impotence
• Priapism
• Hematuria/hyposthenuria
• Renal concentrating and acidifying defects
• Retinopathy
• Acute chest syndrome (infection/infarction), leading to chronic pulmonary disease
• Infections (pneumonia, osteomyelitis, meningitis, pyelonephritis); sepsis
• Hemosiderosis (2 to multiple transfusions)
• Decreased intelligence, even without stroke
• Splenic infarction can occur by 10 years of age.
• Substance abuse related to chronic pain
PATIENT MONITORING
• Determined by number/severity of crises
• It is important to recognize and treat infections early. Parents and patients should be instructed that a temperature of 101F (38.3C) requires immediate medical attention.
• All febrile patients require cultures (blood/urine), chest radiograph, and CBC/reticulocytes.
• For patients who receive chronic transfusions, monitor for hepatitis and hemosiderosis.
• Begin periodic eye evaluations at age 5 to detect proliferative sickle retinopathy (1,3)[C].
REFERENCES
1. American Academy of Pediatrics, Section on Hematology/Oncology. Health supervision of children with sickle cell disease. Pediatrics. 2002;109:526-535.
2. Johnson CS, ed. Sickle cell disease. Hematol Oncol Clin North Am. 2005;19(5).
3. National Institutes of Health. The management of sickle cell disease, 4th ed. 2002. NH Publ# 02-2117.
4. Bonds DR. Three decades of innovation in the management of sickle cell disease. Blood Rev. 2005;19:99-110.
5. Stop Trial Investigators. Discontinuing prophylactic transfusions used to prevent stroke in sickle cell disease. N Engl J Med. 2005;353(26):2769-2778.
6. Fischbach F. Nurse's Quick Reference to Common Laboratory and Diagnostic Tests, 3rd ed. Philadelphia: Lippincott, 2002.
7. Smeltzer SC, Bare BG, Hinkle JL, Cheever KH. Brunner Suddarth's Textbook of Medical-Surgical Nursing, 11 ed. Philadelphia: Lippincott Williams Wilkins, 2005.
8. Vichinsky EP. Pulmonary hypertension in sickle cell disease N Engl J Med. 2004;350(9):857-859.
9. Stuart MJ, Nagel RL. Sickle-cell disease. Lancet. 2004;364(9442):1343-1360.
ANEMIA, PERNICIOUS
ANEMIA, PERNICIOUS - Abdulrazak Abyad, MD, PhD, MBA, MPH, AGSF
BASICS
DESCRIPTION
Pernicious anemia is a disorder due to vitamin B12 deficiency. It is invariably associated with atrophic gastritis and histamine-fast achlorhydria. Vitamin B12 cannot be absorbed in the terminal ileum without intrinsic factor (a secretion of the parietal cells of the gastric mucosa). Its usual course is slowly progressive.
• System(s) Affected: Gastrointestinal; Hematologic/Lymphatic/Immunologic; Nervous
• Synonym(s): Addison anemia; Megaloblastic anemia due to B12 deficiency
ALERT
Geriatric Considerations
More common in this age group and often in association with other autoimmune disorders, depression, and dementia
Pediatric Considerations
• Juvenile pernicious anemia occurs in older children and is the same in most respects as in adults.
• Congenital pernicious anemia is usually evident before 3 years of age.
Pregnancy Considerations
Untreated pernicious anemia in pregnancy may cause neural tube defects.
GENERAL PREVENTION
• Early detection of anemia
• Workup of anemia
EPIDEMIOLOGY
Predominant sex: Male = Female
Incidence
Unknown
Prevalence
Older adults (>60 years)
RISK FACTORS
• Vegetarian diet, without B12 supplementation
• Gastrectomy
• Blind loop syndrome
• Fish-tapeworm infestation
• Malabsorption syndromes
• Drugs: Oral calcium-chelating drugs, amino salicylic acid, and biguanides
• Chronic pancreatitis
• Alcoholism
Genetics
• HLA-DR2, HLA-DR4: Present in the rare form of pernicious anemia that is hereditary
• Endemic area: Northern Europe, including Scandinavia
ETIOLOGY
• Atrophic gastric mucosa
• Intrinsic factor deficiency
• Probable autoimmunity against gastric parietal cells
• Autoimmunity against intrinsic factor
ASSOCIATED CONDITIONS
• Autoimmune diseases including rheumatoid arthritis, IgA deficiency
• Graves disease
• Myxedema
• Iron deficiency
• Thyroiditis
• Vitiligo
• Idiopathic adrenocortical insufficiency
• Hypoparathyroidism
• Agammaglobulinemia
• Tropical sprue
• Celiac disease
• Crohn's disease
• Infiltrate disorders of the ileum and small intestine
DIAGNOSIS
SIGNS AND SYMPTOMS
History
• Anorexia, weight loss
• Depression
• Position sense: Decreased
• Prematurely gray-haired
• Tinnitus
Physical Exam
• Abnormal reflexes
• Ataxia
• Atrophic glossitis
• Babinski's sign: Positive
• Confusion
• Congestive heart failure
• Dementia
• Exertional dyspnea
• Extremity numbness
• Extremity paresthesias
• Hepatomegaly
• Hypoalqesia in "sock and glove" distribution
• Pallor
• Palpitations
• Poor finger coordination
• Purpura
• Romberg's sign: Positive
• Skin pigmentation increased
• Sore tongue
• Splenomegaly
• Tachycardia
• Vertigo
• Vibration sense: Decreased
• Vitiligo
• Weakness
TESTS
• Schilling test plus intrinsic factor: Normal vitamin B12 absorption
• Schilling test: Decreased vitamin B12 absorption
• Gastric analysis: Achlorhydria
Lab
• Achlorhydria
• Anisocytosis
• Haptoglobin decreased
• Howell-Jolly bodies
• Hypergastrinemia
• Hypersegmented neutrophils
• LDH increased
• Leukopenia
• Macrocytic anemia; MCV: 110-140
• Pentagastrin stimulation: Stomach pH >6
• Serum ferritin increased
• Serum vitamin B12 level 100 pg/mL (74 pmol/L)
• Peripheral blood smear: Macro-ovalocytes
• Poikilocytes
• Thrombocytopenia
• Anti-intrinsic poikilocytosis factor antibody
• Anti-parietal cell antibody
• Direct hyperbilirubinemia
• Disorders that may alter lab results
- Falsely elevated MCV
Cold agglutinins
Hyperglycemia
Marked hyperleukocytosis
- Falsely normal serum vitamin B12 level
Myeloproliferative disorders
Liver disease
- Falsely low serum B12 level
Multiple myeloma
Oral contraceptive intake
Pregnancy
Folate deficiency
Transcobalamin I deficiency
Recent isotope administration
Diagnostic Procedures/Surgery
• Bone marrow aspiration
• Detailed history and physical exam
Pathological Findings
• Bone marrow: Hypercellular, macrocytes, iron stores increased
• Nests of megaloblasts
• Giant metamyelocytes
• Macro-polymorpho-leukocytes
• Hypersegmented neutrophils
• Stomach: Atrophic gastritis, goblet cells increased
• Parietal cell atrophy
• Chief cell atrophy
• Gastric cytology: Cellular atypia
• Spinal cord: Myelin degeneration of the dorsal and lateral tracts
• Peripheral nerve degeneration
• Degenerative changes of the posterior root ganglia
DIFFERENTIAL DIAGNOSIS
• Folic acid deficiency
• Myelodysplasia
• Neurological disorders without B12 deficiency
• Liver dysfunction
• Hypothyroidism
• Hemolysis or bleeding
• Drug effects
• Alcoholism
TREATMENT
GENERAL MEASURES
• Appropriate health care: Outpatient
• Treatment must be continued for life
• Identification and treatment of the underlying disorder
ALERT
Folic acid treatment without vitamin B12 in patients with pernicious anemia is contraindicated.
Diet
Emphasize meat, animal protein foods, and legumes unless contraindicated.
Activity
Unlimited
MEDICATION (DRUGS)
• Parenteral Vitamin B12 (cyanocobalamin)
- 1,000 mcg SQ for each dose
- Administer daily for the 1st week
- Administer weekly for 1 month
- Monthly injections for remainder of life (patients may be taught to give self-injection)
• Precautions: Do not give folic acid supplements without vitamin B12, may cause fulminant neurological deficit.
FOLLOW-UP
PROGNOSIS
• Anemia reversible with parenteral vitamin B12
• Neurologic effects not reversible with parenteral vitamin B12
COMPLICATIONS
• Hypokalemia may complicate the 1st week of treatment.
• Central nervous system symptoms may be permanent if patient is not treated in 6 months after the symptoms begin.
• Gastric polyps
• Stomach cancer
- There is a 3-fold likelihood of developing gastric carcinoma.
- Suggest endoscopy approximately every 5 years even if asymptomatic.
PATIENT MONITORING
• Monthly injections of vitamin B12
• Endoscopy every 5 years to rule out gastric carcinoma
REFERENCES
1. Bennett JC, Plum F, eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: WB Saunders; 1996.
2. Chui CH, Lau FY, Wong R, et al. Vitamin B12 deficiency-need for a new guideline. Nutrition. 2001;17:917-920.
3. Wheby MS, ed. The Medical Clinic of North America: Anemia. Vol. 76. Philadelphia, PA: WB Saunders; 1992.
4. Williams WJ, Beutler E, Erslev AJ, et al., eds. Hematology. 4th ed. New York, NY: McGraw-Hill; 1990.
MISCELLANEOUS
See also: Tropical Sprue
