*7.2.2.2.1 Corticosteroids*

Systemic corticosteroids are not recommended for chronic or maintenance treatment of atopic dermatitis due to many common side effects associated with their use and possible rebound flaring upon discontinuation (Akdis et al, 2006). Typical side effects include; osteoporosis, cataracts, growth suppression, and poor wound healing. A short course of systemic corticosteroids with taper is recommended to abort an acute flare-up. Recommended dosing with prednisone is 40 to 60 mg daily for three to four days followed by 20 to 30 mg daily for three to four days can be beneficial.

#### *7.2.2.2.2 Cyclosporine*

Cyclosporine has proven beneficial in attenuating exacerbations in adults and children with severe atopic dermatitis. It also may be used for intermittent chronic not just short-term therapy. Cyclosporine is classified as a calcineurin inhibitor, which blocks T cell activation. A dose of 5mg/kg/day divided every 12 hours has been evaluated. Monitoring of trough levels, renal, and hepatic function is essential. A taper by 1mg/kg/day every one to three months is recommended. (Sowden et al, 1991; Brazelli et al, 2002). Common side effects associated with cyclosporine include increased risk of infection, malignancy, nephrotoxicity, hypertension, and seizures.

#### *7.2.2.2.3 Interferons*

Interferon-gamma (IFN-gamma) works by suppressing T helper cell activity along with other immunomodulatory effects (Schmitt 2007). Interferon-gamma (IFN-gamma) has shown varying results in the treatment of severe atopic dermatitis although a couple of trials have shown a reduction in symptoms and body surface involvement (Hanifin et al 1993). Side effects that may occur include granulocytopenia, fever/chills, myalgias, headache, and inject site pain.

Several biological therapies have been studied for severe atopic dermatitis and only a few have shown benefit in small subset of patients. Further studies are necessary before any of these medications can be routinely recommended. Some of the biological therapies that have been evaluated are Omalizumab, Rituximab, Infliximab, Etanercept, Alefacept, and Mepolizumab (Graves et al 2007).

#### *7.2.2.2.4 Antimetabolites, azathiaprine, and methotrexate*

Antimetabolites azathioprine and methotrexate have shown usefulness in severe atopic dermatitis. Azathioprine is an antagonist of purine metabolism that inhibits T cell

Clinical Management of Atopic Dermatitis 263

of inhibition of IL-4; synthesis inhibitors, binding site inhibitors, and inhibiting intracellular signal transduction. Suplatast tosylate is an example of a synthesis inhibitor developed in Japan and may prove useful for steroid resistant asthma, but data about possible effects in atopic dermatitis are lacking. There are several compounds being studied as therapeutic agents inhibiting the binding site and signal transduction (Hennekes & Asadullah 2002).

If AD is not appropriately treated there can be several complications that can arise. It is shown that patients with atopic dermatitis are more susceptible to microorganisms, particularly S. aureus. Untreated lesions can result in bacterial infections, and acute inflammatory responses of the skin. Patients with atopic dermatitis can also present with eyelid dermatitis, nipple dermatitis, and cheilitis of the lips. Eyelid dermatitis and chronic blepharitis can result in visual impairment from corneal scarring. Other ocular complications include atopic keratoconjunctivitis, vernal conjunctivitis, and keratoconus (Leung, et al. 2003). Management of AD is important in the prevention of other conditions.

Patient education, in addition to treatment, is a factor that can drastically help improve the health of any patient. The healthcare practitioner plays a very important role in a patients' improvement of atopic dermatitis. They can assist a patient in determining what the causative agent is, and provide counselling on how to avoid that particular agent. A physician's knowledge on appropriate diagnosis and the available treatment options is very important in ensuring optimal care. As the drug experts, pharmacists are also responsible for the care of the patient. By providing practical advice concerning the appropriate use of drug products, such as topical corticosteroids and calcineurin inhibitors, compliance can be optimized and adverse effects minimized. In addition, the pharmacist can diminish the stress and anxiety often experienced by patients and caregivers, particularly parents of infants and children with atopic dermatitis. In addition, a pharmacist can advise undiagnosed or untreated patients' on when it is necessary to

Atopic dermatitis is a condition that has no cure, but the main goal of treatment is to reduce disease flares and improve the patients' quality of life. Avoidance of triggering factors, optimal skin care, and pharmacotherapy can produce control of exacerbations in patients. Although there is no cure, there are many safe and effective treatment options available. Corticosteroids remains the standard for therapy, but those unresponsive to corticosteroids have other options including systemic and topical immunomodulators, and non-

Akdis C., Bieber T., Akdis M., et al. Diagnosis and treatment of atopic dermatitis in children

and adults: European Academy of Allerogology PRACTALL Consensus Report. *J* 

**8. Complications** 

**9. Role of a clinician** 

receive treatment from a physician.

**10. Conclusion** 

prescription agents.

**11. References** 

proliferation. Methotrexate is a folic acid antagonist that inhibits reactions and promotes release of adenosine. It also inhibits lymphocyte proliferation. Adverse effects associated with azathioprine and methotrexate are myelosupression, hepatotoxicity, gastrointestinal disturbances, and increased risk of infection. Monitoring of hematologic and liver function tests is mandatory (Hon et al 2009; Weatherhead et al 2007).

#### **7.3 Emerging therapies**

As discussed, atopic dermatitis is an important skin disorder that leads to significant costs and morbidity to patients, families, and society. Effective therapeutic agents are limited in number, and all have side effects that impede successful long-term use. Consequently, there is a high medical need for better therapies. Bimosiamose, nanocrystalline silver cream, phosphodiesterase-4 inhibitors, and IL-4/IL-3 receptor blockers are considered here.

### **7.3.1 Bimosiamose**

Bimosiamose is a selectin antagonist that blocks the initial slowing of leukocyte traffic, preventing leukocytes from migrating into the tissue, and may alter cell activation and cellcell signalling pathways. Currently Bimosiamose is in Phase II clinical testing for asthma, psoriasis, and atopic dermatitis (Revotar Biopharmaceuticals 2011).

#### **7.3.2 Nanocrystalline silver cream**

Nanocrystalline Silver Cream completed preliminary studies evaluating its use in atopic dermatitis. Silver has proven for decades to be an effective antimicrobial agent. It has been the active ingredient for the treatment of burns and other wounds. It has also demonstrated anti-inflammatory activity in animal studies. Human studies are currently in Phase II trials evaluating nanocrystalline silver cream applied twice daily using placebo, 0.5% or 1% cream (ClinicalTrials.gov 2005).

## **7.3.3 Phosphodiesterase-4 Inhibitors**

Phosphodiesterases play a key role in degrading cAMP, which is an important process in virtually all the cell types involved in the pathophysiology of allergic and inflammatory diseases including asthma and chronic obstructive pulmonary disease (COPD), but also skin diseases such as psoriasis and atopic dermatitis. PDE-4 is the major and most abundant in almost all inflammatory and immune cells. PDE-4 suppresses several pro-inflammatory mechanisms like cytokine generation and secretion, IgE production, proliferation, and histamine generation just to name a few. Topical and systemic therapies are being studied. One general problem is the group associated side effect profile with nausea, emesis, and enhanced gastric acid production being the most critical commonly occurring with systemic therapies. Some examples are topical Atizoram and orally Arofylline. The newly FDA approved Roflumilast (Darilesp®) for severe COPD is being investigated for its utility in atopic dermatitis (Baumer et al 2007).

#### **7.3.4 Interleukin receptor blockers**

Elevated IgE responses and eosinophilia is observed in many patients with atopic dermatitis. This is thought to reflect the increased expression of Th2 cytokines, in particular IL-4, IL-5, and IL-13. Cutaneous infiltration of activated T-cells and their release of cytokines are thought to be key events in the development of atopic dermatitis. There are three ways of inhibition of IL-4; synthesis inhibitors, binding site inhibitors, and inhibiting intracellular signal transduction. Suplatast tosylate is an example of a synthesis inhibitor developed in Japan and may prove useful for steroid resistant asthma, but data about possible effects in atopic dermatitis are lacking. There are several compounds being studied as therapeutic agents inhibiting the binding site and signal transduction (Hennekes & Asadullah 2002).
