Tacrolimus Versus Hydrocortisone in Atopic Dermatitis
Condition: Atopic; Dermatitis
MeSH terms: Dermatitis, Atopic; Dermatitis
Study type: Interventional
Phase: Phase 4

Summary: 
      Atopic dermatitis (AD) is a very common inflammatory, genetic skin disorder that occurs more
      frequently in children. Its exact etiology is not known but it is characterized by pruritic
      skin reactions with elevation in the levels of inflammatory markers. Corticosteroids are the
      first line and the mainstay therapy in management of atopic dermatitis but have many local
      and systemic adverse effects. The study aims to evaluate the efficacy and safety of topical
      tacrolimus ointment in comparison to topical hydrocortisone cream in management of children
      diagnosed with atopic dermatitis.
    

Detailed description: 
      Atopic dermatitis is a common pruritic inflammatory skin disorder. The prevalence of atopic
      dermatitis increased in the last three decades by two or three folds worldwide. In the
      developed countries, atopic dermatitis is estimated to affect 15% to 30% of children and 2%
      to 10% of adults. This type of dermatitis is usually associated with family history of other
      atopic disorders such as allergic rhinitis or asthma.

      The clinical presentation of Atopic dermatitis differs depending on the age of the patient,
      it usually begins in infancy with erythematous, papular skin rash that may first appear on
      the cheeks and chin. In childhood, the skin appears dry, flaky, rough, cracked, and may bleed
      because of scratching, in adults the lesions are more diffuse with underlying erythema.

      This condition is characterized by acute phase where the skin has red scaly patches and
      chronic phase in which the skin thickens.

      Atopic dermatitis is a complex genetic disease where the exact etiology is not entirely
      known, but it is most probably due to interaction between environmental and genetic factors.
      The two major groups of involved genes are the genes encoding for epidermal and epithelial
      structural proteins and the genes regulating the production of cytokines for the immune
      response.

      In atopic dermatitis patients, imbalance occurs between T helper-1 (TH1) and T helper-2 (TH2)
      immune responses, increased TH2 activity causes the release of interleukin (IL)-3, IL-4,
      IL-5, IL-10, and IL-13 which results in blood eosinophilia, increased total serum
      immunoglobulin (Ig) E, and increased growth and development of mast cells.

      Atopic dermatitis patients are more likely to develop different skin infections as compared
      to healthy individuals, including: staphylococcal secondary bacterial infections and herpes
      simplex viral infection.

      Topical corticosteroids (TCS) are the mainstay for management of atopic dermatitis to which
      other treatments are compared, they act by many pathways to reduce inflammation. Although TCS
      are effective treatment, they have both local adverse effects as skin thinning, striae,
      perioral dermatitis, acne, rosacea, telangiectasias, purpura and focal hypertrichosis.
      Moreover, systemic absorption can lead to systemic effects such as
      hypothalamic-pituitary-adrenal (HPA) axis suppression, infections, hyperglycemia, cataracts,
      glaucoma, and growth retardation (in children).

      All these side effects are more likely to occur with prolonged use and so seeking for other
      treatment options is crucial.

      Topical calcineurin inhibitors (TCI) as tacrolimus and pimecrolimus are immunosuppressives
      that help to control the acute flares and decrease the severity of the new flares by acting
      as immunomodulators. They inhibit the calcineurin so inhibit the T-cell proliferation that
      produces many inflammatory cytokines such as IL-2, IL-3, IL-4, IL-17, tumor necrosis factor
      (TNF). TCI is more selective as compared to TCS with less adverse effects so it is considered
      as an acceptable alternative to TCS.

      Tacrolimus 0.03% ointment is approved for moderate to severe atopic dermatitis for ages 2
      years and older, with the 0.1% ointment limited to ages 16 years and older; pimecrolimus 1%
      cream is approved for mild-to-moderate atopic dermatitis for ages 2 years and older. There is
      limited data comparing TCS with tacrolimus or pimecrolimus.

      The FDA has a black box warning for both tacrolimus ointment and pimecrolimus cream about
      their potential local skin carcinogenesis as seen in animal studies. However, till now there
      is no causal relationship has been proven between use of a TCI and the development of
      lymphoma or non-melanoma skin cancer.

      This study aims to assess the efficacy and safety of topical tacrolimus ointment in
      comparison to topical hydrocortisone cream in children diagnosed with atopic dermatitis. The
      primary outcome is to evaluate the effect of topical tacrolimus ointment as compared to
      topical hydrocortisone cream by estimation of the serum level of inflammatory cytokines and
      the effect on the dermatitis severity scale. The secondary outcome is to evaluate the
      tacrolimus safety as compared to hydrocortisone through the assessment of treatment related
      toxicities.
    

Intervention name(s): Tacrolimus; Hydrocortisone
Intervention type(s): Drug; Drug
Intervention description(s): 0.03% topical tacrolimus ointment applied on the affected areas twice daily for 4 months.; 1% hydrocortisone cream applied on the affected areas twice daily for 4 months.
Other intervention name(s): Tacrolimus (Tacrolimus 0.03%®) was manufactured by AL-Andalous company for pharmaceutical and chemical industries, Egypt.; Hydrocortisone (Micort 1%®) was manufactured by Cid company for pharmaceutical and chemical industries, Egypt.
Intervention MeSH terms: Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Tacrolimus
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: prospective, double blinded, simply randomized clinical trial
Masking: Double (Participant, Care Provider)
Primary purpose: Treatment
Keywords: Tacrolimus; Hydrocortisone; Atopic; Dermatits; children