FDA Experience: Topical Corticosteroids and HPA Axis Suppression

1
Rx Topical Corticosteroids
HPA Axis Suppression and Cutaneous Effects
Denise Cook, M.D. Medical OfficerDivision of
Dermatology and Dental Drug Products
2
OUTLINE

• Background
• Class Labeling for Topical Corticosteroids
• HPA Axis Suppression The FDA Experience
• Trial Data from Approved Drug Products
• Resultant Labeling Changes
• Postmarketing Summary
• Cutaneous Adverse Events from Topical
  Corticosteroid Use

3
Topical Corticosteroid Classification

• Seven Classes
• Class I Superpotent
• Class II High Potency
• Classes III, IV, V, VI Midpotency
• Class VII Low Potency
• Vasoconstrictor Assay

4
Cosyntropin Stimulation Test

• Used to assess the function of the end organ -
  the adrenal gland - in the hypothalamic-pituitary-
  adrenal axis
• In the case of topical corticosteroids, assessing
  an exogenous unwanted treatment effect
• Cosyntropin 0.125 mg or 0.25 mg is administered
  IV at baseline and end of treatment
• Blood is drawn for serum cortisol values at 30
  minutes and sometimes 60 minutes post stimulation
• Interpretation of the results determines a normal
  or abnormal response

5
Evolution of Interpretation of Normal Function
of the HPA Axis

• 1985
• am serum cortisol
• Urinary corticoid concentrations
• 1996 Cosyntropin Stimulation Test
• 30 minute post stimulation serum cortisol gt 20
  µg/dL
• If prestimulation serum cortisol 20 µg/dL, then
  needed a 6ug/dL increment
• 1999
• 30 minute post stimulation cortisol gt 18 µg/dL

6
Evolution of Interpretation of Normal Function
of the HPA Axis

• 2001 - Cosyntropin Stimulation Test
• Control plasma cortisol level should exceed 5
  µg/100mL
• 30 minute level should show an increment of at
  least
• 7 µg/100mL
• 30 minute level should exceed 18 µg/100mL
• 2004
• 30 minute level should exceed 18 µg/100mL

7
Class Labeling for Rx Topical Corticosteroids -
1990

• Effects on the HPA Axis
• Effects on Glucose Metabolism
• Development of Cushings Syndrome
• Effects on Growth
• Effects on Intracranial Pressure

8
Two open-label trials withTemovateTM Ointment

• Trial 1
• 6 adult patients with psoriasis applied 7
  grams/day to 30 BSA for 7 days
• ACTH stimulation was performed at baseline and 2
  post-treatment A.M. cortisols
• 3/6 or 50 of patients exhibited decreases in
  cortisol production

9
Two open-label trials with TemovateTM Ointment
(contd)

• Trial 2
• Objective - determine the largest dose over a 7
  day period that would not cause significant
  suppression of the adrenal gland
• 3 doses were used - 7 grams/day, 3.5 grams/day,
  2.0 grams/day
• Suppression was determined by A.M. plasma
  cortisol levels and urinary corticoid
  concentrations
• None of the psoriatic patients suppressed at 7.0
  grams/day or 3.5 grams/day but doses as low as
  2.0 grams/day caused marked suppression of
  cortisol secretion in patients with atopic
  dermatitis.

10
Temovate Label - 1985

• TEMOVATETM (clobetasol cream and ointment),
  0.05, a Class I steroid
• PRECAUTIONS General TEMOVATETM is a highly
  potent topical corticosteroid that has been shown
  to suppress the HPA axis at doses as low as 2 g
  per day.
• Pediatric Use Use of TEMOVATETM Cream and
  Ointment in children under 12 years of age is
  not recommended.

11
Class Label Precautions Section
12

• General Systemic absorption of topical
  corticosteroids can produce reversible
  hypothalamic-pituitary-adrenal (HPA) axis
  suppression with the potential for gluco-
  corticosteroid insufficiency after withdrawal
  from treatment. Manifestations of Cushing's
  syndrome, hyperglycemia, and glucosuria can also
  be produced in some patients by systemic
  absorption of topical corticosteroids while on
  treatment.

13

• Patients applying a potent topical steroid to a
  large surface area or to areas under occlusion
  should be evaluated periodically for evidence of
  HPA axis suppression. This may be done by using
  the ACTH stimulation, A.M. plasma cortisol, and
  urinary free cortisol tests.

14

• If HPA axis suppression is noted, an attempt
  should be made to withdraw the drug, to reduce
  the frequency of application, or to substitute a
  less potent steroid. Recovery of HPA axis
  function is generally prompt upon discontinuation
  of topical corticosteroids. Infrequently, signs
  and symptoms of glucocorticosteroid insufficiency
  may occur requiring supplemental systemic
  corticosteroids.

15

• Class Label
• Pediatric Use Section

16

• Safety and effectiveness in children and infants
  have not been established. Because of a higher
  ratio of skin surface area to body mass, children
  are at a greater risk than adults of
  HPA-axis-suppression when they are treated with
  topical corticosteroids. They are therefore also
  at greater risk of glucocorticosteroid
  insufficiency after withdrawal of treatment and
  of Cushing's syndrome while on treatment.

17

• HPA axis suppression, Cushing's syndrome, linear
  growth retardation, delayed weight gain, and
  intracranial hypertension have been reported in
  pediatric patients receiving topical
  corticosteroids. Manifestations of adrenal
  suppression in pediatric patients include low
  plasma cortisol levels to an absence of response
  to ACTH stimulation. Manifestations of
  intracranial hypertension include bulging
  fontanelles, headaches, and bilateral
  papilledema.

18
Topical Corticosteroid DataHPA Axis Suppression

• 10 drug products
• 8 topical corticosteroid products
• 2 topical combination drug products
• 11 studies
• Ages 3 months adult
• Open-label trials
• Cosyntropin stimulation test

19
Topical Corticosteroid Drug Products

• Dermatop a mid potency steroid
• Cutivate Cream a mid potency steroid
• Diprolene AF Cream a high potency steroid
• Diprosone Ointment a high potency steroid
• Diprosone Cream a mid potency steroid
• Diprosone Lotion a mid potency steroid
• Clobex Lotion a super potent steroid
• Temovate E Cream a super potent steroid

20

• Dermatop (prednicarbate emollient cream), 0.1
• a Class V steroid
• Approved May 1996
• Pediatric Atopic Dermatitis Trial

21

• 59 pediatric patients enrolled
• 2 targeted populations
• - patients between 1 month and 2 years
• - patients between 2 and 12 years
• 10 patients were lt2 years old
• 49 patients were 2 years old

22
Treatment Criteria

• gt20 body surface area (BSA) involvement
• Twice daily for 21 consecutive days
• ACTH Stimulation Test
• Cosyntropin administered at baseline and day 22
• Patients 15 kg received 0.25 mg IV
• Patients lt 15 kg received 0.125 mg IV

23
Criteria per protocol for a normal adrenal
response to ACTH stimulation at 30 and 60 minutes

• Post stimulation serum cortisol gt20 µg/dL
• If pre-stimulation serum cortisol levels gt 20
  µg/dL, an incremental increase gt6 µg/dL in serum
  cortisol

24
Three patients according to the protocol criteria
were suppressed 2 patients, 1 an 18 month old,
had a peak response of 5 µg/dL change from
baseline. 1 patient had a post-stimulation
cortisol value that decreased from baseline. At
that time, the Agency agreed with an outside
endocrinologist that since these 3 patients had a
post-stimulation response that was greater than
20 µg/dL, although they didn't have the required
incremental rise, they would not be
considered suppressed. This led to the current
label that reads that "none of the 59 patients
showed evidence of HPA axis suppression."
25
Cutivate (fluticasone) Cream, 0.05 a Class V
steroid Approved June 17, 1999 Pediatric Atopic
Dermatitis and Psoriasis Trial
26

• 43 patients were evaluable ( all with moderate to
  severe atopic dermatitis)
• 29 patients 3 months to 2 years old
• 14 patients 3 years to 5 years old

27
Treatment Criteria

• At least 35 BSA involvement
• Bid application for 3 - 4 weeks
• Patients up to 2 years limited to
• 120 grams/week
• Patients 3-5 years of age limited
• to 180 grams/week

28
BSA Improvement Over Time(N46)

• 23 (50) had a decrease of 50 by 2 weeks
• 9 (20) had a decrease of 50 by 3 weeks
• 4 (9) had a 50 decrease by 4 weeks

29
Cosyntropin Stimulation Test

• Test administered at baseline and
• end of treatment
• Younger age group given 0.125 mg cosyntropin IV
• Older age group given 0.25 mg cosyntropin IV

30
Normal responseCosyntropin Stimulation Test
A serum cortisol level gt18 µg/dL at 30 minutes
post-stimulation
31
2 out of 43 patients experienced adrenal
suppression
Serum Cortisol (?g/dL) Serum Cortisol (?g/dL) Serum Cortisol (?g/dL) Serum Cortisol (?g/dL) Serum Cortisol (?g/dL) Serum Cortisol (?g/dL)
Baseline Baseline End-Tx End-Tx Follow-up Follow-up
Subject Age/Sex BSA Severity Duration Amt. Used Pre-stim Post-stim Pre-stim Post-stim Pre-stim Post-stim
B201 5 yrs/M 95 (95) 22 (9) 4 weeks 561.0 grams 22.1 33.9 7.1 11.8 2.1 19.8
B202 2 yrs/M 35 (35) 17 (7) 5 weeks 176.5 grams 10.8 28.6 2.1 9.4 LTF LTF
32
Label Change for Cutivate Cream

• Indication Children as young as 3 months of age
  for up to 4 weeks of use
• Safety Update Information Precautions General
  and Pediatric Use Sections

33
Betamethasone Propionate - Approved in 2001

• Diprolene AF Cream, 0.05 - a Class II steroid
• Diprosone Ointment, 0.05 - a Class II steroid
• Diprosone Cream, 0.05 - a Class III steroid
• Diprosone Lotion, 0.05 - a Class V steroid
• Lotrisone Cream and Lotion (clotrimazole and
  betamethasone propionate)

34
Criteria for a Normal HPA Axis Response

• Follow the Cortrosyn label
• Failure of any one of 3 criteria would indicate
  suppression of the HPA axis
• Stimulation should occur at baseline and end of
  treatment

35
Criteria - 30 minute post-stimulation

• The control plasma cortisol level should exceed 5
  µg/100 mL
• The 30-minute level should show an increment of
  at least 7 µg/100mL
• above the basal level
• The 30-minute level should exceed
• 18 µg/100mL

36
Diprolene AF Cream, 0.05

• 60 evaluable patients,
• ages 1-12 years with atopic dermatitis
• Mean BSA involvement - 58
• (range 35 - 95)
• Used study drug bid for 2 - 3 weeks
• Limited to 45 grams/week

37
Diprolene AF Cream, 0.05 (contd)

• 19/60 or 32 of these patients showed evidence of
  HPA axis suppression
• 11/19 (58) had a post-stimulation plasma
  cortisol value lt 18 µg/dL
• 6/19 (32) failed to have an incremental change
  of at least 7 µg/dL
• 2/19 (11) had a pre-stimulation cortisol
• lt 5 µg/dL

38
Suppression by Age Group
Age Group 3mo-1 yr n4 2yr-5yr n16 6yr-8yr n28 9yr-12yr n12
suppressed 2 6 9 2
50 38 32 17

• Recovery of normal HPA axis function
• 4 patients were retested 2 weeks post- treatment
  and 3 of the 4 recovered normal function of the
  HPA axis.

39
Statistical Analysis in the Development of HPA
Axis Suppression

• No correlation between amount of drug used, body
  weight, age or sex and the incidence of adrenal
  gland suppression
• Statistical relationship did exist between BSA
  and risk of HPA axis suppression
• for an increase of 1 BSA involved, risk of HPA
  axis suppression increased 4.4
• p 0.01

40
Label Change for Diprolene AF Cream, 0.05

• Indication - added an age restriction to 13 years
  and older
• Clinical Safety Information - Updated in the
  Clinical Pharmacology, Precautions General and
  Pediatric Use Sections

41
Diprosone Ointment, 0.05

• 53 evaluable subjects with atopic dermatitis
• Age Range - 6 months to 12 years old
• Medication applied bid for 2 to 3 weeks
• Mean BSA Involvement - 58 (range
• 35 - 99)

42
Diprosone Ointment, 0.05 (contd)

• 15/53 or 28 of patients showed evidence of HPA
  axis suppression
• 8/15 or 53 had a post-stimulation plasma
  cortisol value lt 18 µg/dL
• 7/15 or 47 failed to have an incremental change
  of at least 7 µg/dL

43
Suppression by Age Group
Age Group 3mo-1 yr n11 2yr-5yr n21 6yr-8yr n15 9yr-12yr n6
suppressed 4 6 4 1
36 29 27 17
44
Statistical Analysis in the Development of HPA
Axis Suppression

• No statistically significant effect for
• Drug usage
• BSA
• Weight
• Age
• Higher proportion of males than females (p0.006)
  who developed HPA axis suppression

45
Recovery of HPA Axis FunctionDiprosone Ointment

• 2/15 patients were retested
• 100 recovery at 2 weeks

46
Label Change Diprosone Ointment, 0.05

• Indication - added an age restriction to 13 years
  and older
• Clinical Safety Information - Updated in the
  Clinical Pharmacology, Precautions, General and
  Pediatric Use Sections

47
Diprosone Cream, 0.05

• 43 evaluable patients with atopic dermatitis
• Age Range - 1 year to 12 years old
• Mean BSA Involvement - 40 (range
• 35 - 90)
• Medication applied bid for 2-3 weeks

48
Diprosone Cream, 0.05 (contd)

• 10/43 or 23 of patients showed evidence of
  adrenal suppression
• 5/10 or 50 had a post-stimulation plasma
  cortisol value lt 18 µg/dL
• 3/10 or 30 failed to have an incremental change
  of at least 7 µg/dL
• 2/10 or 20 had a pre-stimulation cortisol
• lt 5 µg/dL

49
HPA Axis Suppression by Age
Age Group 3mo-1yr n3 2yr-5yr n20 6yr-8yr n13 9yr-12yr n7
suppressed 0 6 3 1
0 30 23 14
50
Statistical Analysis in the Development of HPA
Axis Suppression

• No statistically significant effect for
• Number of days treated
• Weight
• Age
• Statistical significance found for mean amount of
• drug used - 81 grams vs. 37 grams (plt0.001)
• There was a numerically higher BSA involvement
• Numerically, more males developed suppression

51
Recovery of HPA Axis FunctionDiprosone Cream

• 2/10 patients were retested
• 1/2 (50) recovered HPA axis function at 2 weeks

52
Label Change Diprosone Cream, 0.05

• Indication - added an age restriction to 13 years
  and older
• Clinical Safety Information - Updated in the
  Clinical Pharmacology, Precautions, General and
  Pediatric Use Sections

53
Diprosone Lotion, 0.05

• 15 evaluable patients with atopic dermatitis
• Age Range - 6 to 12 years old
• Mean BSA Involvement - 45 (range
• 35 - 72)
• Medication applied bid for 2-3 weeks

54
Diprosone Lotion, 0.05 (contd)

• 11/15 or 73 of patients showed evidence of HPA
  axis suppression
• 10/11 or 91 had a post-stimulation plasma
  cortisol value lt 18 µg/dL
• 1/11 or 9 failed to have an incremental change
  of at least 7 µg/dL

55
Suppression by Age Group
Age Group 3mo-1 yr n0 2yr-5yr n0 6yr-8yr n10 9yr-12yr n5
suppressed None enrolled None enrolled 7 4
- - 70 80
56
Statistical Analysis in the Development of HPA
Axis Suppression

• Numerical analysis
• Subjects exhibiting HPA axis suppression
• Larger mean amount of drug used (92.8 g vs. 69.4
  g)
• Slightly higher BSA involved (45.8 vs. 41.8)
• Lower mean weights at visit 1 (65 lbs. vs. 81
  lbs.)
• Lower mean weights at visit 4 (65 lbs. vs. 80
  lbs.)
• Differences with respect to age and days of
  treatment were miniscule

57
Recovery of HPA Axis FunctionDiprosone Lotion

• 6/11 patients were retested
• 4/6 (67) recovered HPA axis function at 2 weeks

58
Label Change Diprosone Lotion, 0.05

• Indication added an age restriction to 13 years
  and older
• Clinical Safety Information Updated in the
  Clinical Pharmacology, Precautions General and
  Pediatric Use Sections

59
Comparison of HPA Axis CriteriaBetamethasone
Dipropionate
60
Lotrisone Cream

• Tinea Pedis Study
• Tinea Cruris Study
• Both studies were in the adolescent population
  ages 12 16 years
• Medication was applied twice daily
• Study duration
• 4 weeks for tinea pedis
• 2 weeks for tinea cruris

61
Lotrisone Cream (contd)

• 17/43 (39.5) demonstrated adrenal suppression in
  the tinea pedis study
• 8/17 (47.1) demonstrated adrenal suppression in
  the tinea cruris study

62
Label ChangeLotrisone Cream and Lotion

• An Expanded Indications Section
• Added an age restriction patients 17 years and
  older
• Recommended that effective treatment may be
  obtained without the use of a corticosteroid for
  noninflammatory tinea infections
• Updated Safety Information Precautions
  General, Pediatric Use, Geriatric Use and Dosage
  and Administration Sections

63

• Clobex (clobetasol propionate), Lotion 0.05
• a Class I steroid
• Approved July 24, 2003
• Atopic Dermatitis and Psoriasis Trials

64
Clobex Lotion

• 3 studies
• 2 adult studies one in psoriasis and one in
  atopic dermatitis
• 1 pediatric study (ages 12 17 years) in atopic
  dermatitis
• Comparator drug Temovate E Cream
• Class I steroid
• Same chemical moiety, clobetasol propionate
• Different vehicle, an emollient cream

65
Construct of HPA Axis Evaluation

• The control plasma cortisol level should exceed 5
  micrograms/100 mL
• The 30 minute level should show an increment of
  at least 7 micrograms/100 mL above basal level
• The 30 minute level should exceed 18
  micrograms/100 mL
• Exceptions
• plasma cortisol levels were drawn at 60 minutes
  post-stimulation.
• In adult studies, subjects were stimulated with
  cosyntropin weekly.

66
Adolescent study

• 24 evaluable patients 14 treated with Clobex
  Lotion and 10 treated with Temovate E Cream
• Moderate to severe atopic dermatitis
• BSA treated at least 20
• Medication applied BID for 2 weeks
• 50 grams/week limit

67
HPA axis suppression

• 9/14 (64) of subjects treated with Clobex Lotion
  suppressed
• 2/10 (20) of subjects treated with Temovate E
  Cream suppressed

68
Statistical Analysis

• Mean BSA treated was higher for patients with
  adrenal suppression
• 32.8 vs. 27.7 for Clobex Lotion
• 35 vs. 25.3 for Temovate E Cream

69
Recovery of HPA Axis Function

• 1/4 of patients treated with Clobex Lotion
  remained suppressed after 2 weeks
• 1/1 patient retested after treatment with
  Temovate E Cream recovered

70
Adult Study

• 18 evaluable patients 9 treated with Clobex
  Lotion and 9 treated with Temovate E Cream
• Moderate to Severe Atopic Dermatitis
• Mean BSA treated 19.3 for Clobex Lotion and
  19.4 for Temovate E Cream
• Medication applied BID for 2 weeks
• 50 gram/week limit

71
HPA Axis Suppression

• 5 / 9 (56) of subjects treated with Clobex
  Lotion suppressed
• 4 / 9 (44) of subjects treated with Temovate E
  Cream suppressed

72
Recovery of HPA Axis Function

• 1 / 3 patients on Clobex Lotion failed to recover
  function 7 days post treatment
• 2 /2 patients on Temovate E Cream recovered
  function 7 days post treatment

73
Adult Study

• 20 evaluable patients 10 treated with Clobex
  lotion and 10 treated with Temovate E Cream
• Moderate to Severe Plaque Psoriasis
• Mean BSA treated 16.2 for Clobex Lotion and
  17.9 for Temovate E Cream
• Medication applied BID for 4 weeks
• 50 gram/week limit

74
HPA Axis Function

• 8 / 10 (80) of subjects treated with Clobex
  Lotion suppressed
• 3 / 10 (30) of subjects with Temovate E Cream
  suppressed
• 1 / 2 subjects with Clobex Lotion retested
  remained suppressed after 8 days
• 0 / 3 subjects on Temovate E Cream were retested

75
Label for Clobex Lotion

• Indication restricted to patients 18 years or
  older
• 2 consecutive weeks not to exceed 50 grams (50 mL
  or 1.75 fl. Oz) per week
• Moderate or severe psoriasis, for localized
  lesions lt 10 BSA can be treated an additional 2
  weeks
• Updated Safety Information Indications and
  Usage, Precautions General and Pediatric Use,
  and Dosage and Administration Sections

76

• Postmarketing Summary
• HPA Axis Suppression
• Sources
• AERS Database
• Medical Literature Case Reports

77
Adverse Event Reporting System(AERS)

• Spontaneous, voluntary surveillance system
• Voluntary reporting by health care professionals
  and consumers
• Mandatory reporting by manufacturers
• Approximately 3 million reports in database
• Database origin 1969
• Contains human drug and therapeutic biologic
  reports exception vaccines (VAERS)
• Quality of a report is variable and often
  incomplete
• Subject to under-reporting (true numerator not
  known)
• Duplicate reporting occurs

78
Postmarketing SummaryHPA Axis Suppression

• 94 cases spanning 3 decades
• 65 adult cases
• 29 pediatric cases
• Manifestations
• Adrenal insufficiency
• Cushings Syndrome
• Growth Retardation

79
Postmarketing ReportsPediatric Cases

• 29 pediatric patients
• 11 with adrenal insufficiency
• 17 with Cushings Syndrome
• 13 with Growth Retardation
• Characteristics
• Age range 6 weeks 15 years mean age 5.0 years
• duration of use 22 days 7.5 years mean use
  20.8 months
• 16 (55) received medication for 3 months or
  longer
• Varied indications but 34 used topical steroids
  for diaper rash
• Betamethasone containing, clobetasol, and
  mometasone products implicated most often, with
  34 using high potency topical steroids
• Resulted in 14 hospitalizations and 2 deaths, the
  latter from Cushings Syndrome

80
Postmarketing ReportsAdult Cases

• 65 adult cases
• 46 with adrenal insufficiency/suppression
• 32 with Cushings Syndrome
• Characteristics
• Age range 19 years 74 years mean age 47.4
  years
• duration of use 7 days 12.0 years mean use
  35.6 months
• 30 (46) received medication for 3 months or
  longer
• Varied indications but 51 used topical steroids
  for psoriasis
• Betamethasone containing and clobetasol products
  implicated most often, with 61 using high
  potency topical corticosteroids
• Resulted in 34 hospitalizations and 2 deaths
• Deaths attributed in part to the adrenal event

81
Postmarketing ReportsCommon Factors in Adverse
Events

• Most AEs occurred in the setting of one or more
  of the following
• Prolonged use of topical corticosteroid
• Use of a super potent topical corticosteroid
• Use of multiple topical corticosteroid products
  or concomitant use with other corticosteroid
  formulations
• Use of an excessive amount or possible
  inappropriate use of the topical corticosteroid
  product

82
Summary HPA Axis Suppression

• HPA axis suppression does occur with the use of
  topical corticosteroids
• The adrenal suppression is not limited to the
  super potent class of topical corticosteroids
• High BSA involvement and amount of drug used
  appear to be risk factors for HPA axis suppression

83
Summary HPA Axis Suppression

• The type of vehicle may contribute to the extent
  of absorption of the active chemical moiety
• The suppression appears, in most cases, to be
  reversible upon cessation of drug usage
• Long-term use of topical corticosteroids,
  particularly high potency ones, can lead to
  serious morbidity and even death

84
Cutaneous Safety

• Known cutaneous adverse events
• Question of cutaneous malignancy

85
Cutaneous Safety

• Adverse Events associated with topical
  corticosteroid use
• Atrophy of the skin
• Telangiectasia
• Striae
• Erythema of the face
• Steroid Rosacea
• Hypopigmentation
• Infection
• Retarded Wound Healing

86
Pictorial Presentationfrom University of
Erlangen Websiteand Bolognia Textbook of
Dermatology
87
Atrophy
88
Telangiectasia
89
Striae
90
Striae
91
Facial Erythema
92
Facial Erythema
93
Steroid Rosacea
94
Hypopigmentation
95
Other Adverse Effects

• Topical corticosteroids placed on certain
  infections, e.g. tinea infections, may exacerbate
  them
• Topical corticosteroids placed on open or
  surgical wounds will retard healing
• Use of topical corticosteroids in the periorbital
  area may cause an increase in intraocular pressure

96
Cutaneous Malignancy Postmarketing Reports

• 2 reports in AERS database as of February 5,
  2005 US Cases
• A 7 month old male with a history of mastocytoma
  was diagnosed with skin cancer several months
  after discontinuation of clobetasol
• A female of unknown age used betametasone cream
  for psoriasis and reported what started as
  psoriasis became cancer
• AERS data do not suggest a compelling safety
  signal for malignancy formation with the use of
  topical corticosteroids

97
Cutaneous Adverse Events

• Corticosteroid induced AEs
• Can be an early or late event
• Depends on potency of drug and duration of use
• Depends on site of application
• Occlusion at the site may increase risk
• Corticosteroid induced AE
• May resolve slowly
• May not resolve

98
Conclusion HPA Axis Suppression

• Can occur with short term use of topical
  corticosteroids
• Can occur with even mid-potency topical steroids
• Can occur as early as two continuous weeks of
  therapy

99
ConclusionHPA Axis Suppression

• Is usually reversible
• The interrelationship between BSA, amount of drug
  used, and potency of medication is complex
• Long term use and/or misuse of topical
  corticosteroids, particularly those of high
  potency, can lead to serious medical
  complications and death

100
ConclusionCutaneous Adverse Events

• Can be related to both duration of use and
  potency of topical corticosteroid
• Can occur with short-term or long-term use
• Resolution is possible with some but not all of
  these cutaneous events
• There is no firm evidence to date to link
  cutaneous malignancy with use of topical
  corticosteroids

101
Rx Topical Corticosteroids
HPA Axis Suppression and Cutaneous Effects