Cellulitis

Aka: Cellulitis, Staphylococcal Cellulitis, Streptococcal Cellulitis

1. See Also
   1. Skin Infection
   2. Hand Infection
   3. Nodular Lymphangitis
   4. Erysipelas
   5. Impetigo
   6. Preseptal Cellulitis and Periorbital Cellulitis
   7. Cellulitis in Diabetes Mellitus
2. Epidemiology
   1. Accounts for 2% of all Emergency Department visits
3. Risk factors
   1. See Skin Infection
   2. Also see Group A Streptococcus Cellulitis (Erysipelas)
   3. Trauma
      1. Laceration
      2. Puncture Wound
      3. Post-operative infection at incision site
   4. Underlying skin lesion
      1. Superficial Folliculitis or Furuncle (Staphylococcus infection)
      2. Skin Ulcer
      3. Fungal Dermatoses
      4. Non-Group A Streptococcus Cellulitis related lesions
         1. Coronary Artery bypass with saphenous vein graft
         2. Radical pelvic surgery or radiation
   5. Neoplasms
      1. Lymphatic Cutaneous metastases from neoplasms
      2. Inflammatory Breast Cancer
      3. Carcinoma Erysipeloides
   6. Extremity Stasis or Edema
      1. Chronic Dependent Edema (may progress rapidly)
      2. Peripheral Vascular Disease
      3. Lymphedema
   7. Perianal Streptococcal Cellulitis (in children)
   8. Diabetes Mellitus
      1. See Cellulitis in Diabetes Mellitus
   9. Immunocompromised patients
4. Causes: General
   1. Common (most Cellulitis cases)
      1. Staphylococcal Cellulitis (typically with abscess)
      2. Group A Streptococcus Cellulitis (Erysipelas)
   2. Less common Streptococcal infections
      1. Pneumococcus
      2. Non-Group A Streptococcus Cellulitis
         1. Group C or G Streptococcus Cellulitis
         2. Group B Streptococcus Cellulitis in newborns
   3. Rapidly progressive Cellulitis
      1. See Necrotizing Fasciitis
      2. Vibrio Cellulitis (Vibrio vulnificus)
      3. Clostridium perfringens
      4. Pasteurella multocida
      5. Aeromonas Hydrophila
5. Causes: Exposure
   1. See Nodular Lymphangitis
   2. See Pet-Borne Infection
   3. See Dermatologic Manifestations in Returning Traveler
   4. Fish Handlers or water exposure (See Marine Trauma)
      1. Erysipelothrix rhusiopathiae (Erysipeloid, fish handler's disease)
      2. Mycobacterium marinum (Fish tank exposure)
      3. Aeromonas Hydrophila
      4. Spines of stonefish (South Pacific) risk of serious systemic toxicity, pulmonary edema
      5. Vibrio vulnificus (Vibrio Cellulitis, high risk of rapid progression)
      6. Vibrio alginolyticus
      7. Vibrio parahaemolyticus
      8. Streptococcus iniae (from farmed tilapia)
   5. Gardening or splinter exposure
      1. See Nodular Lymphangitis
      2. Nocardia brasiliensis (Nocardiosis)
      3. Sporotrichosis: Sporothrix schenckii (fungus)
      4. Tetanus
   6. Hospitalized patients
      1. Methicillin Resistant Staphylococcus Aureus (MRSA)
      2. Pseudomonas aeruginosa
      3. Enterococcus
      4. Escherichia coli
   7. Animal Bites
      1. See Marine Envenomation
      2. Cat Bites
         1. Pasteurella multocida
      3. Dog Bite Infection
         1. Mixed Bacterial flora (Staphylococcus, Streptococcus, Anaerobes)
         2. Pasteurella multocida
         3. Capnocytophaga canimorsus (DF-2)
         4. Staphylococcus intermedius
      4. Human Bites
         1. See Fight Bite
         2. Mixed Anaerobes and aerobes
            1. Staphylococcus aureus and Streptococcus
            2. Bacteroides, Fusobacterium, Eikenella corrodens
   8. Miscellaneous
      1. Eosinophilic Cellulitis
      2. Pseudomonas aeruginosa
         1. Sweaty Tennis Shoe Syndrome
6. Causes: Immunocompromised Patients
   1. Serratia
   2. Proteus
   3. Enterobacteriaceae
   4. Cryptococcus
   5. Legionella pneumophila
      1. Associated with Legionella pneumonia
   6. Legionella micdadei
      1. Seen in renal transplant patients
   7. Escherichia coli
      1. Seen in children with relapsing Nephrotic Syndrome
7. Symptoms
   1. Inflamed Skin Wound develops rapidly days after injury
      1. Local tenderness
      2. Pain (contrast with Pruritus of other skin conditions)
      3. Very red, hot, swollen an painful
      4. Unilateral
   2. Associated symptoms
      1. Malaise
      2. Fever, chills
8. Signs
   1. Draw margins of erythema with marker
      1. Follow course of infection on antibiotics (but do not expect significant improvement in first 24 hours)
   2. Wound with contiguous inflammation
      1. Erythema (Rubor)
      2. Swelling (Tumor)
      3. Local tenderness (Dolor)
      4. Warm to touch (Calor)
   3. Unilateral involvement
      1. Contrast with stasis and edematous conditions which are bilateral
   4. Abscess (or purulent drainage)
      1. Hallmark of Staphylococcus aureus
   5. Peau d'orange Skin (orange-peel like skin)
      1. Cellulitis results in edema including the fat layer
      2. Hair Follicles remain anchored to the Dermis
      3. Results in an indentation or pitting at each Hair Follicle in the midst of edema of the surrounding tissue
   6. Regional spread
      1. Ascending lymphangitis
      2. Regional Lymphadenopathy
   7. Small patches of necrosis
   8. Gram Negative superinfection may also be present
   9. Hemorrhagic and necrotic bullae (specific conditions)
      1. Group A Streptococcal Cellulitis
      2. Pseudomonas Cellulitis
      3. Vibrio Cellulitis (Vibrio vulnificus)
      4. Clostridium perfringens
      5. Aeromonas Hydrophila
9. Differential Diagnosis: Non-infectious Conditions
   1. Precautions
      1. Cellulitis is overdiagnosed, with the risk of antibiotic adverse effects (e.g. Clostridium difficile) and Antibiotic Resistance
      2. Consider alternative diagnoses (e.g. Stasis Dermatitis) when bilateral, pruritic, chronic, non-progressive
   2. Vascular Conditions
      1. Venous Insufficiency and Stasis Dermatitis (most common)
         1. Acute stasis appears with bilateral leg erythema
      2. Lipodermatosclerosis
         1. Panniculitis with bilateral, medial ankle erythema
      3. Superficial Thrombophlebitis
      4. Deep Vein Thrombosis
      5. Lymphedema
   3. Dermatologic Conditions
      1. Contact Dermatitis
      2. Insect Bites
      3. Acute Drug Reaction
      4. Eosinophilic Cellulitis
      5. Sweet Syndrome
      6. Shingles
      7. Calciphylaxis
         1. Calcium deposition due to ESRD, DM, Obesity, liver disease, Warfarin
   4. Rheumatologic Conditions
      1. Gouty Arthritis
      2. Relapsing Polychondritis
   5. Miscellaneous
      1. Edematous conditions (e.g. CHF, Cirrhosis)
      2. Erythromelalgia
      3. Inflammatory Carcinoma (metastatic cancer to skin)
      4. Foreign body reaction (mesh, metal, silicone implant)
      5. Familial Mediterranean fever
      6. Erythema Migrans (Lyme Disease)
   6. References
      1. Swadron and DeClerck in Herbert (2017) EM:Rap 17(5): 11-2
      2. Vergidis (2005) Ann Intern Med 142:47-55 [PubMed]
10. Labs
    1. See Laboratory Risk Indicator for Necrotizing Fasciitis ( LRINEC Score)
    2. Pustular drainage or abscess culture
       1. Recommended if antibiotics are being used, systemic symptoms or severe localized findings
    3. Blood Culture (25% sensitivity)
       1. Not recommended in uncomplicated Cellulitis without associated systemic symptoms
       2. Indications (risk of deep tissue involvement)
          1. Severe infection or systemic symptoms or signs (lymphangitis, Sepsis)
          2. Immunocompromised patients or elderly
          3. Patients requiring surgery
          4. Recurrent, persistent or large abscess
          5. Human Bite or Animal Bite
    4. Skin biopsy (25% sensitivity)
       1. Indicated in necrotizing lesions (especially those requiring derbidement)
       2. Obtain sample of leading margin of lesion
    5. Fine Needle Aspiration
    6. Saline injection and aspiration
       1. Listed for historical purposes only (rarely done in clinical practice)
       2. Technique
          1. Leading edge injection and aspiration with saline
       3. Efficacy
          1. May assist diagnosis with Cellulitis
          2. Not useful in Erysipelas
          3. 30% sensitivity from closed lesions (efficacy may be as low as 5%)
       4. Indication
          1. Unusual pathogens suspected
          2. Cellulitis refractory to current antibiotics
11. Imaging
    1. Soft tissue Ultrasound
       1. Abcess formation is consistent with staphylococcal infection
    2. Computed Tomography (CT)
       1. Consider in suspicion of deep space infection
    3. MRI
       1. Consider in suspected Necrotizing Fasciitis
12. Management: General Care
    1. Tetanus prophylaxis
    2. Clean wound site
       1. Copious irrigation
       2. Debride devitalized tissue
       3. Incision and Drainage if deep fluctuant pocket
    3. Compresses
       1. Cool sterile saline dressings decrease pain
       2. Later, moist heat helps localize infection
    4. Consider immobilization and elevation of involved limb
       1. Splinting in a position of function may decrease swelling
       2. Uncommonly done in practice
    5. Consider Corticosteroids in non-diabetic adults with Cellulitis (especially leg Cellulitis)
       1. Associated with faster Cellulitis resolution
       2. Dall (2005) Cutis 75(3): 177-80 +PMID:15839362 [PubMed]
13. Management: Factors affecting antibiotic selection and course
    1. Distinguish Erysipelas, abscess and Cellulitis
       1. Erysipelas (superficial)
          1. Sharply demarcated, bright red, indurated
          2. Typically caused by Group A Streptococcus
             1. Although Staphylococcus aureus can have a similar appearance on the face
       2. Cellulitis (deep, subcutaneous)
          1. Abrupt onset of indistinct faint erythema with rapidly advancing border
          2. Typically caused by group A. Streptococcus or Group G
             1. Although Staphylococcus can cause this as well
       3. Purulent Cellulitis
          1. Cellulitis with pustular drainage or exudate without definitive, drainable abscess
       4. Abscess
          1. Hallmark of Staphylococcus aureus infection
          2. Primary management is Incision and Drainage
          3. If antibiotics are needed (Cellulitis with abscess), then cover MRSA (see below)
       5. Other Bacterial Skin Infections
          1. Folliculitis
          2. Impetigo
    2. Consider exposures in antibiotic selection
       1. Fresh water exposure
          1. Fluoroquinolone
       2. Salt water exposure
          1. Doxycycline
       3. Dog Bite, Cat Bite or Human Bite
          1. Amoxicillin-Clavulanate (Augmentin)
          2. If Penicillin Allergy
             1. Clindamycin or Metronidazole AND
             2. Trimethoprim-Sulfamethoxazole or Fluoroquinolone
    3. Distinguish most likely organism: Streptococcus or Staphylococcus
       1. Streptococcus (especially Group A Streptococcus)
          1. Streptococcus (especially Group A) is the most common cause of Cellulitis and Erysipelas
          2. Abrupt onset with rapid spread
          3. May be associated with fever and ascending lymphangitis
          4. Typically associated with an inciting skin injury with associated break in the skin (e.g. Tinea Pedis)
       2. Staphylococcus aureus (typically MRSA)
          1. Less common cause of Cellulitis (causes only 14% of uncomplicated Cellulitis)
             1. However, purulent drainage or abscess is typically caused by Staphylococcus aureus
          2. Typically presents without a primary skin injury site
          3. Primary source is often a Folliculitis
          4. Abscess is often present (Incision and Drainage is primary treatment)
             1. May present initially as pustular drainage or exudate (pustular Cellulitis)
             2. Consider soft tissue Ultrasound if suspect occult abscess
    4. Consider Antibiotic Resistance
       1. Avoid Fluoroquinolones in Cellulitis due to high resistance
       2. Staphylococcus aureus infections are often due to MRSA
    5. Course: Uncomplicated
       1. Standard course has been 10 days of antibiotics
       2. New: 5 day as effective as 10 day if uncomplicated
          1. Hepburn (2004) Arch Intern Med 164:1669-74 [PubMed]
    6. Course: Complicated
       1. Course 7-14 days (6 weeks if joint involvement)
14. Management: Emergency Department Approach
    1. Factors associated with oral, outpatient treatment failure
       1. Fever with Temperature >38 C at triage (OR 4.3)
       2. Chronic leg ulcers (OR 2.5)
       3. Chronic edema or lympedema (OR 2.5)
       4. Prior Cellulitis in the same area (OR 2.1)
       5. Cellulitis at a wound site (OR 1.9)
       6. Peterson (2014) Acad Emerg Med 21(5):526-31 +PMID:24842503 [PubMed]
    2. Localized, uncomplicated Cellulitis without serious local or systemic findings
       1. Start oral therapy without initial intravenous dose
       2. Single intravenous dose prior to discharge on oral dosing does not speed resolution or improve efficacy
          1. Most oral antibiotics used for Skin Infections have excellent, rapid oral absorption
             1. Examples: Clindamycin, Septra, Doxycycline
       3. Do not empirically start MRSA for uncomplicated Cellulitis without abscess or purulent drainage
          1. Majority of uncomplicated Cellulitis without abscess is caused by Streptococcus
          2. Cephalexin alone has excellent coverage for Streptococcus and MSSA
             1. Added MRSA coverage (e.g. Septra) offers no benefit in non-purulent Cellulitis
             2. Moran (2017) JAMA 317(20): 2088-96 +PMID:28535235 [PubMed]
       4. Do not use a single Vancomycin dose prior to oral antibiotic dosing
          1. Vancomycin serum concentrations after a single dose offer no benefit
             1. Multiple doses are required to reach MIC
          2. Risk of a single Vancomycin dose
             1. Will only lengthen ED time by 60-90 minutes
             2. Increases the risk for Antibiotic Resistance and reactions
    3. Localized Cellulitis with borderline indications for parenteral antibiotics
       1. Start Intravenous Fluids
       2. Give initial oral antibiotic dose
       3. Administer Analgesics
       4. Reassess in 1 hour and reconsider parenteral antibiotics versus discharge on oral antibiotics
    4. Localized Cellulitis with failure to respond to oral therapy
       1. Consider Cellulitis Differential Diagnosis
       2. Maintain same antibiotic course for at least 24-48 hours (unless significant progression)
          1. Cellulitis is unlikely to improve on any antibiotics regimen for the first 24 hours
       3. Assess for Cellulitis with abscess
          1. Consider soft tissue Ultrasound or attempt needle aspiration
          2. Incision and Drainage of abscess
          3. Abscess complicating Cellulitis typically defines Staphylococcal Cellulitis (see antibiotic selection below)
       4. Consider broadening oral antibiotic regimen
          1. Include MRSA coverage if not already added (especially for purulent Cellulitis)
       5. Parenteral antibiotics
          1. See regimens below
          2. Place and IV line and patient returns at intervals (typically every 12 hours) for next antibiotic infusion
          3. Patient returns to ED for infusion only RN visits with a planned recheck by a provider at 24-48 hours
          4. RN alerts provider earlier if concerning findings at time of routine infusion
          5. Admit or place on observation status a patient developing systemic symptoms or other concerning findings
       6. Consider Consultation
          1. Infectious Disease
          2. General Surgery
    5. Consider inpatient management
       1. See below
    6. References
       1. Lin in Herbert (2014) EM:Rap 14(1): 6-7
15. Management: Inpatient
    1. Indications
       1. Cellulitis with serious associated findings or comorbidity
       2. Severe extremity Cellulitis in Diabetes Mellitus
       3. Skin Abscess involving the face, hands, genitalia
       4. Sepsis
       5. Immunocompromised state
    2. Diagnostics
       1. See Laboratory Risk Indicator for Necrotizing Fasciitis ( LRINEC Score)
       2. Complete Blood Count (CBC)
       3. C-Reactive Protein
       4. Comprehensive metabolic panel
       5. Blood Cultures (in severe infections or immunocompromised patients)
       6. Wound aspirate, culture or biopsy (advancing edge)
       7. Imaging indications
          1. Necrotizing Fasciitis (MRI)
          2. Other deep space infection (soft tissue Ultrasound or CT)
    3. Consultation
       1. Consider Consultation with infectious disease
       2. General surgery or orthopedic Consultation indications
          1. Suspected Necrotizing Fasciitis
          2. Suspected Gas Gangrene
          3. Suspected other deep space infection
          4. Suspected joint involvement
    4. Approach
       1. Admit
       2. Incision and Drainage of abscess
       3. Debride necrotic tissue
       4. Intravenous antibiotic regimen as described below (typically with MRSA coverage)
          1. Modify antibiotics based on wound culture results (if performed)
       5. Transition to oral antibiotics
          1. When tolerated and improving
          2. Continue antibiotics for 7-14 day total course
16. Management: Extremity Infections (non-diabetic patients)
    1. See Skin Infections in Diabetes Mellitus
    2. Erysipelas (well demarcated and bright red): Streptococcus coverage
       1. Treat as Cellulitis with broader coverage unless classic Erysipelas appearance
       2. Mild-Moderate infections (oral, oupatient management)
          1. Penicillin VK 500 mg orally four times per day for 7-10 days or
          2. Amoxicillin 500 mg orally three times per day for 7-10 days or
          3. Cephalexin 500 mg orally four times per day for 7-10 days
       3. Penicillin Allergy
          1. Azithromycin 500 mg orally on day 1, then 250 mg orally on days 2-5
          2. Clindamycin 300 mg orally four times per day for 7-10 days
       4. Severe infections (requiring IV antibiotics)
          1. Penicillin G 2 million units IV every 6 hours or
          2. Cefazolin 1 gram IV every 8 hours or
          3. Clindamycin 600 mg IV every 8 hours or
          4. Vancomycin 15 mg/kg IV every 12 hours
    3. Cellulitis (less distinct margins): Streptococcus and Staphylococcus coverage
       1. First Line: Uncomplicated Cellulitis coverage for Streptococcus (most likely) and MSSA coverage
          1. Oral
             1. Cephalexin 500 mg orally four times per day for 7-10 days or
             2. Dicloxacillin 500 mg orally four times per day for 7-10 days or
             3. Amoxicillin-Clavulanate (Augmentin) 875 mg orally twice per day for 7-10 days
          2. Parenteral (more severe infections)
             1. Cefazolin 1 gram IV every 8 hours or
             2. Nafcillin 2 grams IV q4 hours or
             3. Oxacillin 2 grams IV q4 hours
          3. Outpatient parenteral (adults, narrower spectrum parenteral protocol)
             1. Protocol: Both medications for 7-10 days
                1. Cefazolin 2 gram IV q24 hours AND
                2. Probenacid 1 gram PO q24 hours (Decreases Cefazolin excretion)
             2. References
                1. Grayson (2002) Clin Infect Dis 34:1440-8 [PubMed]
       2. Second Line: Complicated, refractory or pustular Cellulitis coverage for Streptococcus and MRSA coverage
          1. Oral (choose 1)
             1. Septra DS 1 tab orally twice daily
                1. Some recommend 2 tabs if normal Renal Function, serious infections or weight >100 kg
                   1. However no advantage found clinically to the higher dosing
                   2. Cadena (2011) Antimicrob Agents Chemother 55(12):5430-2 +PMID: 21930870 [PubMed]
                2. Use with Penicillin, Amoxicillin, or Cephalexin (see dosing above)
             2. Clindamycin 300 mg orally four times per day for 7-10 days (increasing MRSA resistance) or
             3. Linezolid 600 mg orally twice daily
                1. Has been very expensive, but generic in 2017
          2. Parenteral (more severe infections)
             1. Vancomycin 15 mg/kg IV every 12 hours (adjusted for Renal Function) or
             2. Linezolid 600 mg IV q12 hours or
             3. Clindamycin 600-900 mg IV q8 hours
    4. Cellulitis with Abscess (or per Gram Stain): Staphylococcus coverage
       1. See Skin Abscess
       2. Incision and Drainage is primary treatment of solitary abscess (without accompanying Cellulitis)
          1. Antibiotics are not uniformly required if no Cellulitis is present
          2. Antibiotics are at the discretion of the provider and may be warranted despite lack of Cellulitis
             1. Serious comorbidity such as Diabetes Mellitus, immunosuppression or extremes of age
             2. Multiple sites of infection
             3. Systemic symptoms
             4. Rapid progression with concurrent Cellulitis
             5. Infection involving face, hand or genitalia
             6. Associated septic phlebitis
             7. Unreliable follow-up
             8. Large abscess (e.g. 5 cm and greater, Carbuncle)
             9. Failure to improve after Incision and Drainage
          3. Antibiotic selection and course
             1. Antibiotic selection is the same as for abscess with Cellulitis (typically MRSA)
             2. Choose a single agent (esp. Septra)
             3. Course is brief in most cases (3-5 days)
       3. Staphylococcus Cellulitis (purulent Cellulitis) present: MRSA coverage
          1. Septra DS 1-2 tabs twice daily for 7-10 days or
             1. Use 2 tabs if normal Renal Function, serious infections or weight >100 kg
          2. Minocycline of Doxycycline 100 mg twice daily for 7-10 days or
          3. Linezolid 600 mg PO bid (very expensive)
          4. Clindamycin is no longer recommended for MRSA coverage due to growing resistance
             1. Historical dosing Clindamycin 300 mg orally four times per day for 7-10 days
       4. Severe infections
          1. Vancomycin 15 mg/kg IV every 12 hours (adjusted for Renal Function)
          2. Linezolid 600 mg IV q12 hours (very expensive)
          3. Daptomycin
          4. Telavancin
          5. Ceftaroline fosamil
17. Management: Facial erysipelas
    1. Staphylococcus aureus may be difficult to exclude (despite most cases being Group A Streptococcus)
       1. Guidelines as of 2012 recommend covering for MRSA
       2. Sanford guide recommends Vancomycin parenterally or Linezolid orally or IV
    2. Mild to moderate infections
       1. Clindamycin 300 mg orally four times per day or
       2. Augmentin high dose with Septra DS 2 tabs twice daily or
    3. Severe infections
       1. Vancomycin 15 mg/kg IV every 12 hours (adjusted for Renal Function) or
       2. Linezolid 600 mg IV q12 hours
18. Management: Special circumstances (including complicated Cellulitis)
    1. Cellulitis in comorbid Diabetes Mellitus
       1. See Skin Infections in Diabetes Mellitus
    2. Complicated skin and subcutaneous tissue infection (SSTI)
       1. Indications
          1. Deep soft tissue infection
          2. Surgical or Traumatic Wound Infection
          3. Infected ulcers or burns
          4. Large abscess with Cellulitis
       2. Management
          1. Inpatient management is typically indicated
          2. Consider surgical Consultation (and possibly infectious disease Consultation)
          3. Obtain wound cultures
          4. Initiate empiric broad spectrum antibiotic coverage including MRSA
19. Prevention: Recurrent skin and subcutaneous tissue infection (SSTI)
    1. Recurrent infection definition
       1. Two or more discrete episodes of active infection and different sites over a 6 month period
    2. Recurrent abscess
       1. See Skin Abscess for complete list of preventive strategies
       2. Wash all sheets, towels and clothes after an episode
       3. Dispose of used razors
       4. Consider Antibacterial soap (e.g. Chlorhexidine)
       5. Consider Mupirocin (Bactroban) in nares twice daily for 5 days (decolonization)
    3. Recurrent Cellulitis
       1. See measures above under Recurrent Skin Abscess
       2. Reduce Peripheral Edema (support stockings)
       3. Weight loss
       4. Treat underlying Venous Insufficiency
       5. Good skin hygiene
       6. Prophylactic antibiotics are not recommended
          1. Not typically effective, especially if there is an underlying predisposing condition
          2. Strategies that have been used historically for 4-52 weeks (not recommended)
             1. Penicllin G 1.2 MU IM every 4 weeks or Penicillin V 250 mg orally twice daily
             2. Macrolides (e.g. Erythromycin 500 mg orally daily) was used as alternative in Penicillin Allergy
20. Complications:
    1. Thrombophlebitis in older patients
    2. Necrotizing Fasciitis
21. References
    1. Chan (2014) Crit Dec Emerg Med 28(9): 2-7
    2. Gilbert (2011) Sanford Guide
    3. Moran in Majoewsky (2013) EM:Rap 13(2): 11
    4. Orman and Hayes in Herbert (2015) EM:Rap 15(4):4-6
    5. Ramakrishnan (2015) Am Fam Physician 92(6): 474-83 [PubMed]
    6. Stulberg (2002) Am Fam Physician 66(1):119-24 [PubMed]