ANTHRAX - Benjamin L. Sapers, MD
BASICS
DESCRIPTION
• Anthrax is a highly infectious disease of animals, especially ruminants (hooved animals such as cows, goats, sheep, etc.) that is caused by the bacteria Bacillus anthracis. Cutaneous (95% of US cases); inhalational, and gastrointestinal forms can be transmitted to man by contact with the animals or their products.
• Synonym(s) for skin anthrax: Charbon; Malignant pustule; Siberian ulcer; Malignant edema; Splenic fever; Milzbrand; Ragpicker disease
• Synonym(s) for chest anthrax: Woolsorter disease
GENERAL PREVENTION
• Anthrax vaccine protects against all forms of anthrax and is as safe as other vaccines, according to the Food and Drug Administration, the Centers for Disease Control and Prevention, and the National Academy of Sciences. A 2005 review by the Cochrane Infectious Disease Group concluded that the anthrax vaccine is effective in reducing the risk of contracting anthrax and has a low rate of adverse effects (1)[A].
• Vaccine is given in 6 doses (0, 2, and 4 weeks, and 6, 12, and 18 months) plus annual boosters.
- If you get behind schedule, don't start the series over; begin where you left off (delays don't reduce the resulting protection).
- Redness up to 1 inch (1 cm) wide occurs in 30% of men and 60% of women, and redness or other reactions >5 inches (4 cm) occur in ~1% of people (both male and female).
- Anthrax vaccine often causes a nodule under the skin where the vaccine is injected; this can last from 2-3 months. These nodules eventually resolve.
- The Advisory Committee on Immunization Practices recommends vaccination for the following groups
Persons who work directly with the organism in the laboratory
Persons who work with imported animal hides or furs in areas where standards are insufficient to prevent exposure to anthrax spores
Persons who handle potentially infected animal products in high-incidence areas
Military personnel deployed to areas with high risk for exposure to organisms (when used as a biologic warfare weapon)
Pregnant women should be vaccinated for anthrax only if absolutely necessary.
• Patients with a likely exposure history but no symptoms are candidates for postexposure prophylaxis with either ciprofloxacin 500 mg PO b.i.d. or doxycycline 100 mg PO b.i.d.
EPIDEMIOLOGY
• Cutaneous (skin): 95% of cases in the US; cases of cutaneous anthrax without occupational risk should raise concern for a terrorist attack. About 5-20% of untreated cases result in death.
• Gastrointestinal (GI): Very rare in the US (no documented case in the 20th century).
• Inhalational (chest) anthrax is very rare in US; must be considered a bioterrorist event in US until proven otherwise (the last US occupational case occurred in 1976). Death results in 99% of untreated cases, and in 45-80% of patients with severe symptoms who are treated in a state-of-the-art facility.
• Anthrax is most common in agricultural regions, where it occurs in animals. These regions include the Middle East, Asia, Southern and Eastern Europe, Africa, South and Central America, and the Caribbean.
RISK FACTORS
• Contact with infected animals or their products
• Bioterrorist event
PATHOPHYSIOLOGY
• Bacillus anthracis is a spore-forming, gram-positive bacterium found in the soil worldwide. The word anthracis is derived from a Greek word meaning "coal," which is used to describe the cutaneous form of the disease that leads to a characteristic black lesion.
• B. anthracis has 3 known virulence factors: An antiphagocytic capsule and 2 protein toxins (known as edema factor and lethal factor).
- The capsule provides resistance to phagocytosis.
- Lethal factor and edema factor are named for the effects they induce when injected into experimental animals.
- A protein called protective antigen binds to the host cell's surface; when cleaved by a protease on the cell surface it creates a binding site to which the lethal factor and edema factor can bind; protective antigen is required for the action of the 2 protein toxins.
• B. anthracis spores introduced into the host are ingested at the exposed site by macrophages and then germinate into vegetative forms that produce the virulence factors.
ETIOLOGY
• Skin: Occurs when B. anthracis enters the skin through a cut or abrasion during the handling of animal products (such as meat, wool, or hides infected with B. anthracis)
• GI: Ingestion of bacillus-contaminated meat
• Chest: Inhalation of aerosolized B. anthracis spores
DIAGNOSIS
SIGNS AND SYMPTOMS
• Skin: Begins as a pruritic red-brown papule that enlarges with peripheral erythema, vesiculation, and induration, followed by black eschar formation within 7-10 days of the initial lesion. The papule, blister, and eschar are painless, and cutaneous symptoms may be accompanied by fever, malaise, and headache. A black eschar with massive edema is nearly pathognomonic for cutaneous anthrax.
• GI: Presents as 1 of 2 distinct syndromes oropharyngeal and abdominal. Oropharyngeal syndrome presentation can include fever, edema, ulcer, severe sore throat, and lymphadenopathy resulting in marked unilateral or bilateral neck swelling. Abdominal syndrome may present with fever, malaise, hematemesis, anorexia, severe abdominal pain, and hematochezia or melena.
• Chest: Biphasic presentation, with initial phase featuring nonspecific influenzalike symptoms such as low-grade fever, chills, headache, nonproductive cough, diaphoresis, malaise, chest discomfort, nausea, vomiting, diarrhea, and abdominal pain. This initial phase is followed by the 2nd fulminant phase that includes abrupt onset of high fever, severe dyspnea, hypoxia, hypotension, and death.
History
• Skin: Crucial clinical clues are the rapid evolution of symptoms, lack of pain, occasional massive edema, and the near pathognomonic black eschar. Incubation period is usually immediate but may last up to 1 day.
• GI: Incubation period usually 1-7 days; 2-4 days after onset of symptoms, ascites develop as abdominal pain decreases. Shock and death occur within 2-5 days after onset of symptoms.
• Chest: Incubation period is usually 1 week, but may be as long as 2 months. 2nd portion of the biphasic presentation begins 1-5 days after onset of initial symptoms. There may be a 1-3 day period of improvement after the 1st phase and before the 2nd phase begins. Shock and death occur within 24-36 hours after onset of the 2nd phase.
Physical Exam
• Skin: Red-brown papule, vesicles, or black eschar
• GI: Acute abdomen with rebound tenderness may occur. Ascites present later in course
• Chest: Rhonchi may be present.
TESTS
Lab
Gram stain and culture. A presumptive diagnosis can be made if Gram-positive rods are present that are nonmotile, nonhemolytic, and encapsulated (usually seen with India ink). If antibiotics have been given for >24 hours, perform immunohistochemical staining and/or polymerase chain reaction.
Imaging
• Widened mediastinum on chest radiograph may be present in inhalational anthrax.
• Pleural effusions frequently present in chest anthrax; infiltrates are rare.
• GI: Mesenteric adenopathy on CT scan likely.
DIFFERENTIAL DIAGNOSIS
Skin
Cellulitis
Brown recluse spider bite
Cat-scratch disease
Rat bite fever
Rickettsial spotted fever
Carbuncle
Cowpox
Bullous erysipelas
Tularemia vasculitides
Ecthyma gangrenosum
Orf (a transmissible viral disease of goats and sheep)
TREATMENT
GENERAL MEASURES
Chest and GI anthrax is not known to spread from person to person, so communicability concerns are not an issue during management of the patient. For skin anthrax, avoid contact with the wound or wound drainage.
MEDICATION (DRUGS)
First Line
• Skin: Ciprofloxacin 500 mg PO b.i.d. for 60 days or doxycycline 100 mg PO b.i.d. for 60 days. If systemic involvement, massive edema, or lesions on the head or neck, follow treatment recommendation per inhalational anthrax (2)[C].
• Chest and GI: IV ciprofloxacin 400 mg q12h or doxycycline 100 mg q12h AND 1 or 2 additional antimicrobials such as rifampin, vancomycin, penicillin, ampicillin, chloramphenicol, imipenem, clindamycin, and clarithromycin. May switch to PO when clinically appropriate. Must complete 60-day course (combined PO and IV) (2)[C].
Second Line
Patients being treated for anthrax may also benefit from vaccination as part of their regimen (3)[C].
FOLLOW-UP
PROGNOSIS
• Skin: Death in 5-20% of untreated cases.
• GI: Mortality rates as high as 50% have been reported.
• Chest: Death in 99% of untreated cases.
PATIENT MONITORING
Must monitor patient for 60 days to ensure completion of the treatment course
REFERENCES
1. Jefferson T, Demicheli V, Deeks J, et al. Vaccines for preventing anthrax. [Systematic Review] Cochrane Infectious Diseases Group. Cochrane Database of Systematic Rev. 1, 2006.
2. Centers for Disease Control and Prevention. Update: Investigation of bioterrorism-related anthrax and interim guidelines for exposure management and antimicrobial therapy, October 2001. MMWR Morb Mortal Wkly Rep. 2001;50(42):909-919. Erratum in: MMWR Morb Mortal Wkly Rep. 2001;50(43):962.
3. Centers for Disease Control and Prevention. Use of anthrax vaccine in the United States, ACIP Recommendations. MMWR Recommendations Reports. 2000;49(RR-15):1-20.
ADDITIONAL READING
• The anthrax vaccine immunization program. http://www.anthrax.mil
• Centers for Disease Control and Prevention, Emergency Preparedness and Response. http://www.bt.cdc.gov/agent/anthrax/
• Durning SJ, Roy MJ. Anthrax. In: Roy MJ, ed. Physician's Guide to Terrorist Attack. Totowa, NJ: Humana Press Inc.; 2003.
Friday, January 2, 2009
ANTHRAX
ANOREXIA NERVOSA (AN)
ANOREXIA NERVOSA (AN) - Mary Muscari, PhD, RN, CRNP, CS
BASICS
DESCRIPTION
• Refusal to maintain normal body weight, with associated fear of weight gain, body image disturbance, and amenorrhea
• Restricting and binge-eating/purging subtypes
• System(s) Affected: Cardiovascular; Endocrine; Metabolic; Gastrointestinal; Nervous; Reproductive
GENERAL PREVENTION
Encourage rational attitude about nutrition and weight, minimize weight-related criticism and teasing, moderate overly high self-expectations, enhance self-esteem
EPIDEMIOLOGY
• Predominant age at onset: 13-18 years
• Predominant sex: Female > Male (20:1)
• Global distribution
Incidence
8-19 women, 2 men per 100,000 per year
Prevalence
1% in women, 0.1% in men
RISK FACTORS
• Female gender
• Perceived body image distortions
• Perfectionism, obsessionality, rigidity
• Negative self-evaluation
• Academic and other achievement pressure
• Participation in sports or artistic activities that emphasize leanness or involve subjective scoring
- Ballet, running, wrestling, figure skating, gymnastics, cheerleading, weight lifting
• Parental psychiatric disorder
Genetics
• Underlying genetic vulnerability likely, but not well understood
- 1st-degree female relative with eating disorder increases risk 6- to 10-fold.
PATHOPHYSIOLOGY
Complex relationship between biologic, psychological, and social factors that results in an unrealistic perception of fatness. Subsequent malnutrition leads to disorder of multiple organs.
ETIOLOGY
• Serotonin neuronal systems are implicated.
• Multifactorial withpsychological, biological, genetic, environmental, and social factors
ASSOCIATED CONDITIONS
• Mood disorder
• Social phobia, obsessive-compulsive disorder
• Substance abuse disorder
• High rates of cluster C personality disorders
DIAGNOSIS
SIGNS AND SYMPTOMS
• Onset may be insidious or stress related
• Amenorrhea (primary or secondary)
• Report feeling fat even when emaciated
• Preoccupation with body size, weight control
• Elaborate food preparation and eating rituals
• Extensive exercise
• Weakness, fatigue, cognitive impairment
• Hypothermia, cold intolerance
• Constipation, bloating, early satiety
• Dry skin, scalp hair loss, peripheral edema
• Lanugo hair on extremities, face, and trunk
• Growth arrest, delayed puberty
• Hypotension, bradycardia, murmurs
• Decreased bone density, fractures
History
Ascertain fear of weight gain and/or distorted body image.
Physical Exam
• Often normal
• Vital signs: Bradycardia, orthostatic hypotension, body weight 85% expected
• Cardiac: Dysrhythmias, midsystolic click of mitral valve prolapse
• Skin/extremities: Dry, lanugo, hair loss, edema
• Neurologic and abdominal exams: To rule out other causes of weight loss and vomiting
TESTS
Lab
• No specific test for AN. Most findings are related directly to starvation, dehydration
- All findings may be within normal limits.
• Low serum leuteinizing hormone, follicle-stimulating hormone; low T4 with normal TSH
• Abnormal liver enzymes
• Altered blood urea nitrogen, creatinine clearance; electrolyte disturbances
• Hypoglycemia, hypercholesterolemia, hypercortisolemia, hypophosphatemia
• Low sedimentation rate
• Anemia, leukopenia, thrombocytopenia
• 12-lead ECG to assess for prolonged QT
Imaging
Dual-energy x-ray absorptiometry (DEXA) of bone only if underweight for >6 months to assess for diminished bone density
Diagnostic Procedures/Surgery
• DSM-IV-TR criteria
- Refusal to maintain body weight at or above a minimally normal weight for age, height
- Intense fear of gaining weight even though underweight
- A disturbance in the way body weight/shape is experienced; undue influence of body on self-evaluation or denial of seriousness of low body weight
- Specific types
Restricting: Not engaged in binge-eating or purging behaviors
Binge-eating/purging type: Regularly engages in binge-eating or purging behaviors (see Bulimia information related to these behaviors)
• Screening tools: SCOFF questionnaire, Eating disorder Screen for Primary Care (ESP), Eating Attitudes Test (EAT), Eating Disorder Inventory (EDI)
Pathological Findings
• Osteoporosis/osteopenia, pathologic fractures
• Sick euthyroid syndrome
• Cardiac impairment
DIFFERENTIAL DIAGNOSIS
• Hyperthyroidism,adrenal insufficiency
• Inflammatory bowel disease
• Immunodeficiency, chronic infections
• Malabsorption, diabetes
• CNS lesion
• Bulimia; body dysmorphic disorder
• Depressive disorders with loss of appetite
• Anxiety disorder, food phobia
• Conversion disorder, schizophrenic disorder
ALERT
AN may exist concurrently with chronic medical disorders, such as diabetes, cystic fibrosis.
TREATMENT
GENERAL MEASURES
• Initial treatment goal geared to weight restoration; most are managed as outpatients
• Outpatient treatment
- Interdisciplinary team (primary care physician, mental health professional, nutritionist) (1,2)[B,C]
- Average weekly weight gain goal: 0.5-1.0 kg (1)[C] with stepwise increase in calories
- Cognitive behavioral and/or family-based therapy (2,3)[B]
- Focus on health, not weight gain alone.
- Build trust, treatment alliance,
- Involve patient in establishing diet and exercise goals.
- Challenge fear of uncontrolled weight gain; help the patient to recognize feelings that lead to disordered eating.
- In chronic cases, goal may be to achieve a safe weight rather than a healthy weight.
• Inpatient treatment
- If possible, admit to specialized eating disorders unit (4)[C]
- Monitor vital signs, cardiac function, watch for edema, rapid weight gain (fluid overload)
- Initial bed rest with supervised meals may be necessary.
- Stepwise increase in activity
- Tube feeding or total parental nutrition used only as last resort
- Supportive symptomatic care as needed
Diet
• Goal is stabilization at a healthy weight on a balanced diet with normal eating pattern
• Diminished ruminations about calories, weight; increased enjoyment
Activity
• Monitor activity.
• Stepwise increase as patient gains weight
• Focus on enjoyable activities rather than goal-oriented ones.
MEDICATION (DRUGS)
First Line
• No medications are available that effectively treat patients with AN, but antidepressants may benefit those with comorbid depression (5,6)[C].
• Selective serotonin-reuptake inhibitors such as fluoxetine (Prozac): 10-60 mg may
- Help prevent relapse after weight gain
- Treat comorbid depression or obsessive-compulsive disorder (1,4,6)[C]
- Attend to black box warnings concerning antidepressants and conduct appropriate informed consent if antidepressants are prescribed
Second Line
• Management of osteopenia
- Elemental calcium 1200-1500 mg/d plus MVI containing 800 IU of vitamin D (2,4)[C]
- No indication for bisphosphonates in AN (2)[C]
- Weak evidence for use of HRT (2)[C]
- Psyllium (Metamucil) preparations (1 tbsp) to prevent constipation
FOLLOW-UP
DISPOSITION
Admission Criteria
• Suggested physiologic values: Heart rate 40 bpm, BP 90/60, symptomatic hypoglycemia, potassium 3 mmol/L, temperature 97.0F (36.1C), dehydration, other cardiovascular abnormalities, weight 75% of the expected weight, rapid weight loss, lack of improvement while in outpatient therapy
• Suggested psychological indications: Poor motivation/insight, lack of cooperation with outpatient treatment, inability to eat, need for nasogastric feeding, suicidal plan or intent, severe coexisting psychiatric disease, problematic family environment
ALERT
Pediatric Considerations
• Children often present with nausea, abdominal pain, fullness, and inability to swallow.
• Additional indications for hospitalization: Heart rate 50 bpm, orthostatic BP, hypokalemia or hypophosphatemia, rapid weight loss even if weight not 75% below normal
Geriatric Considerations
Late-onset AN (>50) may be long-term disease, or triggered by death of loved one, marital discord, or divorce.
Discharge Criteria
Lower relapse rate when discharged at expected healthy weights
PROGNOSIS
• Prognosis: ~50% recover; 25% improved; 25% chronically ill
• Mortality: 5-7%
COMPLICATIONS
• Refeeding syndrome
• Cardiac arrhythmia; cardiac arrest
• Cardiomyopathy, congestive heart failure
• Delayed gastric emptying, necrotizing colitis
• Seizures, Wernicke encephalopathy, peripheral neuropathy, cognitive deficits
• Osteopenia, osteoporosis
Pregnancy Considerations
• Fertility may be affected.
• Increased risk for miscarriage, operative delivery, congenital malformations, and low-birth-weight infants; should be managed as high risk
PATIENT MONITORING
• Level of exercise activity
• Weigh weekly until stable, then monthly.
• Depression, self-esteem, suicidal ideation
REFERENCES
1. NICE. Eating disorderscore interventions in the treatment and management of anorexia nervosa, bulimia nervosa and related eating disorders. NICE Clinical Guideline no 9. London: NICE, 2004 (accessed 15 Feb 2006).
2. American Psychiatric Association. Practice Guideline for the Treatment of Patients with Eating Disorders, 3rd ed. 2006, June (accessed Dec 10, 2006).
3. Hay P, Bacaltchuk J, Claudino A, Ben-Tovim D, et al. Individual psychotherapy in the outpatient treatment of adults with anorexia. Cochrane Database Syst Rev. 2003;(4):CD003909.
4. Yager J, Anderson AE. Anorexia nervosa. N Engl J Med. 2005;353:1481-1488.
5. Berkman ND, Bulik CM, Brownley KA, et al. Management of eating disorders. Evidence report/technology assessment No. 135. (Prepared by the RTI International-University of North Carolina Evidence-Based Practice Center under Contract No. 290-02-0016.) AHRQ Publication No. 06-E010. Rockville, MD: Agency for Healthcare Research and Quality, April 2006.
6. Claudino A, Hay P, Lima M, et al. Antidepressants for anorexia nervosa. Cochrane Database Sys Rev. 2006;(1):CD04365.
