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The Role and Topical Management of Staphylococcus aureus in Atopic Dermatitis

Franklynne Vincent, MD, FRCPC

St. Josephís Health Centre, Toronto, ON, Canadas

Introduction

Atopic dermatitis (AD), or eczema, is a common, chronic, relapsing, genetically determined inflammatory skin disorder.1 Staphylococcus aureus (S. aureus) has been implicated as an environmental factor in the etiology of atopic eczema since 1899.2 Atopic skin is susceptible to colonization and infection with S. aureus. This current review will discuss the role of S. aureus in atopic dermatitis and upon understanding this role, topical therapeutic management will be discussed.

Overview of Atopic Dermatitis

  • AD is a common skin condition, affecting 15-30% of children and 2-10% of adults.3
  • AD has a complex pathology involving genetic predisposition, deficient epidermal barrier defenses, impaired innate immunity and abnormal acquired immunity, and environmental factors.4,5 This interplay results in skin barrier impairment and inflammation.
  • The diagnosis of AD is made on clinical grounds. One simple criteria6 states that the individual must have:
    1. Pruritus - the hallmark of AD, plus three or more of the following:
    2. Early age of onset
    3. Typical morphology and distribution (facial and extensor involvement in infants and young children, and flexural lichenification or linearity in adults)
    4. Personal or family history of atopy
    5. Xerosis (dry skin)
    6. Chronic and relapsing course

The Role of Staphylococcus aureus in AD

  • The most common bacteria found on AD skin is S. aureus.7
  • In AD patients >90% are colonized with S. aureus on lesional and nonlesional skin vs. 5% on healthy skin.8
  • The extent of colonization correlates with the disease activity and clinical severity of AD.8,9
  • S. aureus colonization is felt to be both a consequence and a cause of the skin inflammation in AD.10

Reasons for Increased Susceptibility of AD Patients to Staphylococcal Infections

Host Factors Promoting Colonization

  • Defective epidermal barrier
    • Decreased ceramides, the major water retaining lipids of the stratum corneum, leads to increased trans- epidermal water loss (TEWL) and contributes to dry cracked skin, predisposing to colonization.11
    • The pH of the skin surface in AD is high or alkaline, creating a suitable environment for colonization.11
  • Defective innate immune responses
    • The innate immune system of the epidermis is the first-line of defense against skin infections and it activates antimicrobial peptides (AMPs); AMPs are decreased in AD.12
  • Increased synthesis of extracellular matrix adhesins for S. aureus13
  • Environmental factors
    • Patients with severe AD have higher levels of
    • S. aureus in their home environment.14
    • AD patients can be recolonized by family members who have the same strains of S. aureus.15
    • Topical medications contaminated with S. aureus can be a source of re-colonization.16

Contribution of S. aureus to Inflammation

  1. Staphyloccal superantigens (SsAgs) penetrate the skin barrier and add to the exacerbation and persistence of the inflammation in AD by:
    • Massive T cell stimulation
    • Acting as allergens
    • Direct stimulation of antigen presenting cells
    • Expansion of skin-homing cutaneous lymphocyte-associated antigen (CLA) T cells10
  2. Enhancing pruritus
    • IL-31 is able to induce itch in AD and is upregulated by SsAgs.17
  3. Induction of corticosteroid resistance10
  4. Secondary infection by S. aureus
    • Secondary infection occurs when an underlying disease creates the conditions for infection. In AD, these are S. aureus colonization, a disrupted skin barrier, and abnormal immune defenses.10

Management of Staphylococcus aureus in AD

1. Role of Antibiotic Therapy

  • Colonization
    The use of antibiotics alone to clear colonization is not recommended for the following reasons:
    • Colonization is a constant feature of AD and S.aureus is found on nonlesional and lesional skin.8
    • Antibiotics will reduce the load of S. aureus, but alone are unable to improve inflammation.18
    • After antibiotic therapy, AD skin rapidly recolonizes, often with the same toxin-secreting organisms.19
    • Prolonged use of antibiotic therapy increases the prevalence of antibiotic-resistant strains of
    • S. aureus, including methicillin-resistant S. aureus (MRSA).10
  • Combination treatment
    • The rationale for combination treatment with topical steroids and antibiotics is to reduce inflammation and improve the skin barrier function with the steroids, while using antibiotics to reduce the S. aureus load and chronic inflammation.
    • Use of an antimicrobial agent with a low- or mid-potency corticosteroid may potentially allow AD management with a lower strength corticosteroid, mitigating some side-effects associated with higher strength corticosteroid monotherapy.
    • A recent report by Cochrane Database Systematic Review did not find clear evidence of benefit for antimicrobial interventions in AD patients. However, the studies were small and poorly reported and the anticipated benefit may not have been demonstrated.20,21
    • It is well known that combination therapy is commonly used in general practice.22
    • Studies of mild to moderate AD comparing combination treatment consisting of 2% fusidic acid and 1% hydrocortisone acetate with either agent alone found that the combination therapy demonstrated improved efficacy in reducing AD symptoms and
    • S. aureus density.23 This treatment is recommended for a limited period of time (maximum of 2 weeks) to avoid resistance.
  • Secondary bacterial infections in AD
    An oral or topical antibiotic is indicated for patients with evidence of secondary bacterial infection.20
    • A sudden flare in a patientís eczema should heighten the possibility of a secondary infection.
    • Patients may report standard therapy is not working.
    • Symptoms may include intense pruritus, fever, and malaise. Signs include intense erythema, oozing, erosions, honey-coloured crusting, pustules, folliculitis, and abscesses.

2. Role of Anti-inflammatories

  • It has been shown that anti-inflammatories (steroids and calcineurin inhibitors) alone (without the use of antibiotics) may reduce S. aureus colonization.24
  • Proper care of atopic skin can help to prevent increased colonization with S. aureus and secondary infection.

3. Multipronged Approach to AD Management

  • AD management requires a multimodal approach that is both pharmacologic and non-pharmacologic.

Non-Pharmacologic Options for AD Management

  • It is important to take the time and properly educate the patient and family members with verbal, written, and practical demonstrations.
  • Trigger factors should be determined, avoided, and dealt with (e.g., irritants, aeroallergens, foods, infections, and stress).
  • Patients and parents need to be taught how to recognize the signs / symptoms of bacterial (and viral) infections.
  • A multidisciplinary approach is needed at times, e.g., referral to a psychologist or dietician.
  • Mild skin cleansers can help remove dirt, irritants, and microbes.
  • Cool compresses can be applied to oozing, weeping, and vesiculated lesions for 10-15 minutes two to three times a day for one to two days to dry up these areas.

Daily Skin Care and Hydration

  • After a 10 minute lukewarm bath (preferred over a shower), the skin is pat dried and within 3 minutes a moisturizer is applied in one direction (so as not to develop folliculitis if rubbed back and forth).
  • A moisturizer should be free of dyes and fragrances, and applied at least once or twice per day to damp skin after the application of any medicated therapy.
  • Patients have to be educated about the need to apply moisturizers constantly, whether using anti-inflammatory medication or not, in order to help repair and preserve the skin barrier.
  • Moisturizing can reduce the need for steroids.25
  • Studies show that decreased ceramide levels in AD not only contributes to a damaged skin barrier, but it also makes the stratum corneum susceptible to S. aureus colonization.17 This has led to the development of ceramide dominant barrier repair creams. A ceramide emollient added to standard care in place of a moisturizer resulted in clinical improvement in difficult to treat AD children.25

Pharmacologic Options for AD Management

Anti-inflammatories

Corticosteroids
  • Used as first-line management and best for acute flares.
  • Weak or mild potencies (e.g., hydrocortisone) are recommended for the face and skin folds in adults and children, and are regarded as the best strengths for use in infants.
  • Moderate potency (e.g., betamethasone valerate) can be applied to the rest of the body.
  • Higher potencies are reserved mainly for adult use on thick localized lesions and the palms and soles.
  • Vehicle suggestions include creams for acute and subacute lesions; ointments for dry, thick chronic lesions; lotions for hair-bearing areas.
  • Apply only to lesional skin twice daily until there is a response (usually 2-4 weeks), then twice weekly to healed areas for up to 2 months to prevent flares.
  • With long-term use, adverse effects can include skin atrophy, tachyphylaxis, and systemic side-effects.
Topical calcineurin inhibitors (TCIs)
  • Pimecrolimus (1% cream) for mild to moderate AD
    • Indicated for use in AD patients =2 years of age
  • Tacrolimus (0.03% and 0.1% ointment) for moderate to severe eczema
    • 0.03% is used in children aged 2-15 years
    • 0.03% and 0.1% may be used in patients >15 years
  • Useful when steroids fail or in cases of steroid phobia.
  • Unlike steroids, TCIs can be used on all body areas as they do not cause skin atrophy.
  • Used for short-term and intermittent long-term therapy.
  • TCIs can be applied twice daily.
  • TCIs can avert a flare if applied at the first signs of symptoms (e.g., local pruritus and redness).
  • Recent studies confirm their safe and effective use as proactive management for children and adults.
  • If applied to healed yet previously affected lesions twice weekly for a few months, TCIs can help prevent flares.
  • Burning at the site of application is the most common local side-effect and this is transient.
Antimicrobials
  • Topicals - localized lesions
    • Fusidic acid 2% cream 2-3 times/day for 7-10 days
    • Mupirocin 2% cream 2-3 times/day for 7-10 days
    • In clinically infected lesions, as well as other lesions where S. aureus colonization is suspected as a contributing factor, short-term (3 times daily for 2 weeks) combination topical therapy with an antibiotic and corticosteroid is widely used.
    • Resistance to topical antibiotics can be reduced if therapy is restricted to short courses (=14 days). Prolonged or intermittent use must be avoided.26,27
  • Systemics - generalized involvement
    • Cloxacillin, cephalexin, or erythromycin for 7-10 days
  • Be mindful of MRSA and check the resistance profile in the patientís area.
  • Culture affected lesions if MRSA is suspected.
  • Localized lesions are treated with topical antimicrobials twice weekly for 1-2 weeks.
  • Acute, oozing areas can first be compressed before applying the topical treatment.
  • The rest of the skin is managed with topical steroids and moisturizers.
  • If the infection is too extensive, oral agents are used usually for 7-10 days, steroids are applied twice daily to the active lesions, and moisturizers are used on the rest of the skin.

Conclusion

S. aureus acts like a commensal organism on the atopic skin, contributing to the underlying inflammation that is a hallmark of this chronic, complex condition. Taking a proactive approach to the management of AD can keep this organism under control, and in turn control flares.

References

  1. Leung DYM. J Allergy Clin Immunol 105(5):860-76 (2000).
  2. Cork MJ. J Eur Acad Dermatol Venereol 7(Suppl 2):S31-7 (1996 Oct).
  3. Larsen FS, et al. Immunol Allergy Clin North Am 22(1):1-25 (2002 Feb).
  4. Bieber T, et al. Current Allergy and Asthma Reports 9(4):291-4 (2009 Jul).
  5. Barnes K C. J Allergy Clin Immunol 125(1):16-29 (2010 Jan).
  6. Williams, HC et al. Br J Dermatol 131(3):383-96 (1994 Sep)
  7. Aly R, et al. Arch Dermatol 113(6):780-2 (1977 Jan).
  8. Leyden JJ, et al. Br J Dermatol 90(5):525-30 (1974 May).
  9. Cho SH, et al. J Invest Dermatol 116(5):658-63 (2001 May).
  10. Lin YT, et al. Clin Rev Allergy Immunol 33(3):167-77 (2007 Dec).
  11. Elias PM, et al. J Allergy Clin Immunol 121(6):1337-43 (2008 Jun).
  12. Ong PY, et al. N Engl J Med 347(15):1151-60 (2002 Oct).
  13. Cho SH, et al. J Allergy Clin Immunol 108(2):269-74 (2001 Aug).
  14. Leung AD, et al. Clin Exp Allergy 38(5):789-93 (2008 May).
  15. Bonness S, et al. J Clin Microbiol 46(2):456-61 (2008 Feb).
  16. Gilani SJ, et al. Clin Exp Dermatol 30(1):10-3 (2005 Jan).
  17. Boguniewicz M. J Allergy Clin Immunol 125(1):4-13 (2010 Jan).
  18. Leung DY, et al. Br J Dermatol 139(Suppl 53):17-29 (1998 Dec).
  19. Lever R, et al. Br J Dermatol 119(2):189-98 (1988 Aug).
  20. Hanifin JM, et al. J Am Acad Dermatol 50(3):391-404 (2004 Mar).
  21. Birnie AJ, et al. Cochrane Database Syst Rev (3):CD003871 (2008).
  22. Leyden JJ, et al. Br J Dermatol 96(2):179-87 (1977 Feb).
  23. Ramsay C, et al. J Eur Acad Dermatol Venereol 7(Suppl 1):S15-22 (1996).
  24. Hung SH, et al. Ann Allergy Asthma Immunol 98(1):51-6 (2007 Jan).
  25. Boguniewicz M, et al. Semin Cutan Med Surg 27(2):115-27 (2008 Jun).
  26. Sule O, et al. Int J Antimicrob Agents 30(1):78-82 (2007 Jul).
  27. Ravenscroft JC, et al. Br J Dermatol 148(5):1010-7 (2003 May).

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