; Dermatologic and Dental
Documents
Resources
Learning Center
Upload
Plans & pricing Sign in
Sign Out
Your Federal Quarterly Tax Payments are due April 15th Get Help Now >>

Dermatologic and Dental

VIEWS: 7 PAGES: 30

  • pg 1
									        ATOPIC DERMATITIS
Clinical Course and Therapeutic
            Options

                  Bindi M. Nikhar, M.D., FAAP
           Division of Dermatologic and Dental
                   Drug Products, ODE V


Pediatric Subcommittee of the AIDAC
October 29-30, 2003
                        Introduction
• Atopic dermatitis is a chronic
  inflammatory disease of the skin primarily
  seen in the pediatric age group
• Characterized by dry skin, pruritus,
  erythema, edema, scaling, excoriations,
  oozing, lichenification
• Increasing prevalence, rising costs
• Together with asthma and allergic rhinitis
  forms part of the ‘atopic triad’

   Pediatric Subcommittee of the AIDAC
   October 29-30, 2003                         2
                     Epidemiology
• 10-20% of children in industrialized
  countries develop atopic dermatitis
• Rising incidence, commoner in
  higher socioeconomic groups
• Overall clearance 50-60%. 80% of
  children with severe disease
  continue to have lifelong
  exacerbations.
   Pediatric Subcommittee of the AIDAC
   October 29-30, 2003                   3
                             Morbidity
Impact on quality of life occurs at all ages.
• Psychological problems from visible skin
  lesions due to stigmatization
• Itch-scratch cycle
• Sleeplessness, lack of concentration at
  school or work
• Repeated treatments, time involved,
  financial costs


    Pediatric Subcommittee of the AIDAC
    October 29-30, 2003                         4
                                    Cost
• Drain on financial resources of
  patients and health services
• Costs increase with disease severity,
  highest in first few years
• While FDA does not consider
  pharmacoeconomic issues in drug
  approvals, we recognize that cost is
  an important factor in drug
  availability.
   Pediatric Subcommittee of the AIDAC
   October 29-30, 2003                     5
       Clinical Manifestations
• Seen in early infancy, in 50 - 75% of
  cases, age of onset is 6 months or
  younger
• Clearance rate of 60% expected by
  age 16, relapses occur in adulthood
• Worse prognosis – severe childhood
  disease, early onset, concomitant or
  family history of asthma/allergic
  rhinitis, biparental history of atopy
   Pediatric Subcommittee of the AIDAC
   October 29-30, 2003                    6
                 Clinical Features
• Three main age-related stages. Dry
  skin and pruritus associated with all
  stages. Skin barrier function
  decreased, may lead to increased
  absorption of topically applied
  treatments. Usually improves with
  adequate treatment


   Pediatric Subcommittee of the AIDAC
   October 29-30, 2003                    7
                     Clinical Phases
• Infantile Phase ( 0-2 years )
Onset around 3 months of age. Under 6
  months, the face and scalp commonly
  involved, at an older age, limb folds and
  hands involved
Red, scaly, crusted weeping patches with
  excoriations seen on both cheeks and
  extensor surfaces of extremities
Course chronically relapsing and remitting

     Pediatric Subcommittee of the AIDAC
     October 29-30, 2003                      8
      Clinical Phases (cont’d)
• Childhood Phase ( 2-12 years )
   Papular areas in flexural regions common.
  Persistent rubbing and scratching leads to
  lichenified plaques and excoriations
• Adult Phase (puberty onwards)
  Flexural lichenified eczema with facial
  involvement in periorbital regions seen.
  Upper trunk, shoulders, scalp affected
  with chronic remissions and
  exacerbations

   Pediatric Subcommittee of the AIDAC
   October 29-30, 2003                     9
Reported Immunological Features
      of Atopic Dermatitis
• Increased IgE production
• Specific IgE to multiple antigens
• Increased basophil spontaneous histamine
  release
• Decreased CD8 suppressor/cytotoxic number and
  function
• Increased expression of CD 23 on mononuclear
  cells
• Chronic macrophage activation with increased
  secretion of GM-CSF, PGE2 and IL-10
• Expansion of IL-4 and IL-5 secreting Th 2-like
  cells
• Decreased numbers of IFN-gamma-secreting Th
  1-like cells
    Pediatric Subcommittee of the AIDAC
    October 29-30, 2003                        10
Diagnosis of Atopic Dermatitis
•  This requires the presence of three or
   more major and three or more minor
   criteria as defined by Hanifin and Rajka
• Major criteria
1. Pruritus
2. Lichenification
3. Chronic or chronically relapsing course
4. Personal or family history of atopy
   Minor criteria
There are 23 minor criteria
    Pediatric Subcommittee of the AIDAC
    October 29-30, 2003                       11
Management of Atopic Dermatitis

• No single, ideal treatment available
• Each patient should have a flexible
  plan tailored for their need
• Dietary history important, dietary
  manipulation controversial
• Family education important
• Reduce exposure to allergens

   Pediatric Subcommittee of the AIDAC
   October 29-30, 2003                   12
 General Treatment Guidelines
• Moisturizers – are the cornerstone of
  therapy in AD. Frequent use important
  because AD is often accompanied by dry
  skin. Creams, ointments or lotions can be
  used depending on individual needs
• Avoidance of drying bathing products
• Itch control – Distressing symptom, use
  oral antihistamines, try to break the itch-
  scratch cycle

    Pediatric Subcommittee of the AIDAC
    October 29-30, 2003                         13
General Treatment Guidelines (cont’d.)

 • Control of infection – Patients with
   extensive AD are often colonized
   with Staph. aureus. A course of oral
   antibiotics ± topical antibiotics
   needed for lichenified, excoriated
   lesions not responding to treatment.
   Viral infections, eg. warts, eczema
   herpeticum are seen in these
   patients
    Pediatric Subcommittee of the AIDAC
    October 29-30, 2003                   14
         Selection of treatment
This depends on
• Disease severity
• Age
• Compliance
• Efficacy
• Safety data
• Treatment costs

   Pediatric Subcommittee of the AIDAC
   October 29-30, 2003                   15
         Rx Treatment Options
1. Topical corticosteroids
2. Topical immunosuppressants
3. Systemic corticosteroids

Off-Label and other treatment options
1. Photochemotherapy
2. Cyclosporin
3. Azathioprine
4. Thymopentin
5. Interferon-γ therapy
6. Traditional Chinese medicine
7. γ -linoleic acid
   Pediatric Subcommittee of the AIDAC
   October 29-30, 2003                   16
 Topical corticosteroids (TCS)
• First introduced in the 1950s and are
  currently the mainstay of prescription
  therapy for atopic dermatitis
• Safe and effective when used as
  recommended
• Weakest steroid that will keep the eczema
  under control should be used
• Potent steroids should be used in short
  pulses, generally 2-3 weeks

   Pediatric Subcommittee of the AIDAC
   October 29-30, 2003                    17
    Factors to consider when
prescribing topical corticosteroids
1. Type of preparation (base and potency) –
    Base can be ointment, cream, emulsion,
    gel or lotion
   Potency classified from group I (most
    potent) to VII (least potent)
2. Acute or chronic eczema
3. Age of child
4. Site to be treated
5. Extent of eczema
6. Method of application
   Pediatric Subcommittee of the AIDAC
   October 29-30, 2003                    18
    Mechanism of action of TCS
1. Antiinflammatory effects
   TCS affect inflammatory cells, chemical
    mediators and tissue responses which
    are all responsible for cutaneous
    inflammation
2. Antiproliferative effects
   TCS may reduce mitotic activity in the
    epidermis, leading to flattening of the
    basal cell layer and thinning of the
    stratum corneum and stratum
    granulosum

   Pediatric Subcommittee of the AIDAC
   October 29-30, 2003                        19
Mechanism of action of TCS (cont’d)

3. Atrophogenic Effects
 TCS can promote atrophy of the
  dermis through inhibition of
  fibroblast proliferation, migration,
  chemotaxis and protein synthesis




   Pediatric Subcommittee of the AIDAC
   October 29-30, 2003                   20
     Systemic Effects of TCS
• If a TCS is absorbed percutaneously
  in significant quantities, it can cause
  systemic adverse side effects similar
  to systemically administered
  corticosteroids.
Discussed under adverse effects



   Pediatric Subcommittee of the AIDAC
   October 29-30, 2003                   21
       Adverse effects of TCS
Can result from
• the drug substance, or
• the vehicle which can potentiate
     problems




   Pediatric Subcommittee of the AIDAC
   October 29-30, 2003                   22
 Systemic adverse effects of TCS

• Suppression of hypothalamic-
  pituitary-adrenal axis
• Iatrogenic Cushing’s syndrome
• Growth retardation in infants and
  children
These effects are usually associated
  with the large body surface area use
  of potent TCS.
   Pediatric Subcommittee of the AIDAC
   October 29-30, 2003                   23
Risk factors for systemic adverse
              effects
• Young age (infants and children)
• Liver and renal disease
• Amount of TCS applied
• Extent of skin disease treated
• Frequency of application
• Length of treatment
• Potency of drug
• Use of occlusion
It is not established whether catch up
   growth in children will occur when TCS
   are discontinued.

   Pediatric Subcommittee of the AIDAC
   October 29-30, 2003                      24
    Local side effects of TCS
• Epidermal Atrophy - wrinkled skin
  with prominent vasculature,
  pseudoscars, striae or purpura
• Steroid dependence/rebound
• Glaucoma/cataracts
• Increased susceptibility to bacterial,
  fungal and viral infections

   Pediatric Subcommittee of the AIDAC
   October 29-30, 2003                     25
 Topical Immunosuppressants
• Newest pharmacological class for AD
• Introduced in this decade
• Direct immunosuppressive action in
  diseases with immunologic basis
• 2 FDA approved products
• Tacrolimus (FK506) (trade name Protopic)
• Pimecrolimus (SDZ ASM 981) (trade name
  Elidel)


   Pediatric Subcommittee of the AIDAC
   October 29-30, 2003                       26
                        Background
• Protopic (tacrolimus) ointment approved
  on 12/08/2000, 0.03% ointment approved
  for children 2 to 15 years, 0.1% ointment
  approved for adults.
• Indication in both age groups is short and
  intermittent long term therapy of patients
  with moderate to severe AD.
• Systemic tacrolimus (Prograf) first
  introduced for prevention of allograft
  rejection, now used in kidney, liver and
  heart transplantation
   Pediatric Subcommittee of the AIDAC
   October 29-30, 2003                     27
           Background (cont’d)
• Elidel (pimecrolimus) cream 1% approved
  on 12/13/2001
• Indicated for patients 2 years of age and
  older for short and intermittent long term
  therapy in the treatment of mild to
  moderate atopic dermatitis
• Both drugs not approved for use in
  children less than 2 years of age
• Systemic absorption can take place in
  both adult and pediatric age groups from
  topical application of both drugs

   Pediatric Subcommittee of the AIDAC
   October 29-30, 2003                         28
          Background (cont’d.)
• Pediatric patients enrolled in clinical
  studies of tacrolimus and pimecrolimus
  had an increased incidence of certain
  adverse events eg. viral infections
  compared to vehicle.
• Currently, the effects of topical
  immunosuppressants on the developing
  immune system are unknown


   Pediatric Subcommittee of the AIDAC
   October 29-30, 2003                      29
Indications for use (Second-line)
• Both Protopic and Elidel are
  indicated for patients in whom the
  use of alternative, conventional
  therapies are deemed inadvisable
  because of potential risks, or in the
  treatment of patients who are not
  adequately responsive to or are
  intolerant of alternative, conventional
  therapies
   Pediatric Subcommittee of the AIDAC
   October 29-30, 2003                   30

								
To top