|
MEMORANDUM |
DEPARTMENT OF HEALTH AND
HUMAN SERVICES PUBLIC HEALTH SERVICE FOOD AND DRUG
ADMINISTRATION CENTER FOR DRUG EVALUATION
AND RESEARCH |
DATE: July
9, 2001
FROM: Joyce Weaver, Pharm.D., Safety
Evaluator
Division
of Drug Risk Evaluation I, HFD-430
THROUGH: Julie Beitz, M.D., Director
Division
of Drug Risk Evaluation I, HFD-430
TO: Jonathan
Wilkin, M.D., Director
Division of Dermatologic and
Dental Drug Products, HFD-540
SUBJECT: Postmarketing Safety Review—PID
D010141
Drugs:
Topical Corticosteroids
|
Alclometasone
dipropionate Amcinonide Betamethasone
dipropionate Betamethasone
valerate Clobetasol
propionate Clocortolone
pivalate Desonide
Desoximetasone
Dexamethasone
Diflorasone
diacetate Fluocinolone
acetonide Fluocinonide
|
Flurandrenolide Fluticasone
propionate Halcinonide
Halobetasol
propionate Hydrocortisone
Hydrocortisone
butyrate Hydrocortisone
probutate Hydrocortisone
valerate Methylprednisolone
acetate Mometasone
furoate monohydrate Prednicarbate
Triamcinolone
acetonide |
INTRODUCTION/ EXECUTIVE SUMMARY
We
reviewed 202 AERS adverse event reports for the topical corticosteroids
reported for pediatric patients age 0 to 18 years of age. Local irritation and
application site reactions were the most frequently reported events in
pediatric patients. Numerous systemic adverse events were reported, including
striae, Cushing’s syndrome, growth retardation, hyperglycemia, hirsutism,
glaucoma, and adrenal insufficiency. Some cases resulted in serious outcomes,
including hospitalization and death. Long-term application of topical
corticosteroids in high-risk settings (for example, application to the genital
and groin area in very young patients) resulted in numerous adverse events. In
some cases topical corticosteroids were continued despite the failure of the
dermatoses to improve.
We
recommend that the systemic adverse events in the AERS database be included in
the labeling for these products. Additionally, we recommend information be
included on the appropriate duration of use of the products, including the
appropriate duration of use for dermatoses that prove to be unresponsive to
topical corticosteroids.
DRUG INFORMATION/LABELING
The topical corticosteroids are indicated for the relief of inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. Clotrimazole and betamethasone dipropionate cream and lotion are indicated for the topical treatment of symptomatic inflammatory tinea pedis, tinea cruris and tinea corporis due to Epidermophyton floccosum, Trichophyton metagrophytes, and Trichophyton rubrum. Neomycin and polymixin B sufates, bacitracin zinc and hydrocortisone cream and ointment are indicated for the treatment of corticosteroid-responsive dermatoses with secondary infection.
Many of the topical corticosteroid products are not labeled for use in pediatric patients. Alclometasone dipropionate cream and ointment and prednicarbate emollient cream are approved for use in children 1 year of age and older. Mometasone furoate monohydrate cream and ointment are approved for use in children 2 years of age and older. Fluocinolone acetonide topical oil is approved for pediatric patients 6 years of age and older for up to 4 weeks to treat atopic dermatitis. Fluticasone propionate cream is approved for pediatric patients 3 months of age and older for up to 4 weeks. Some products (betamethasone dipropionate ointment, betamethasone dipropionate cream, betamethasone dipropionate gel, betamethasone dipropionate lotion, betamethasone dipropionate and clotrimazole cream and betamethasone dipropionate and clotrimazole lotion, betamethasone dipropionate and clotrimazole cream, betamethasone dipropionate and clotrimazole lotion, clobetasol propionate cream, clobetasol propionate ointment, clobetasol propionate solution, clobetasol propionate gel, and clobetasol propionate foam) are approved in pediatric patients 12 years of age and older.
All of the products include
general information regarding the potential for systemic corticosteroid effects
in pediatric patients in the Warnings,
Precautions, or Adverse Reactions sections of the labeling.
Attachment 1 contains a listing of the topical corticosteroids by generic name, tradename, NDA number, and approval date.
MEDICAL LITERATURE SUMMARY
There are published reports of systemic adverse events
from the topical use of corticosteroids in pediatric patients.
Hypothalamic-pituitary-adrenal (HPA) axis suppression has been observed in
infants and children with both high potency and low potency topical
corticosteroids.1,2,3
Shaffer et al used data from the National Ambulatory
Medical Care Survey to determine the demographic characteristics and diagnoses
of patients who were prescribed betamethasone dipropionate and clotrimazole
cream by family physicians. The study found that family physicians frequently
prescribed betamethasone dipropionate and clotrimazole to children younger than
5 years of age and for use on genital skin disorders.4
SELECTION OF CASE SERIES
We searched AERS on May 16,
2001 for adverse event reports for topical corticosteroids in patients age 0 to
18 years of age. We retrieved 234 unique reports from AERS. Thirty-two reports
were excluded because the patient had not used topical corticosteroids prior to
experiencing the adverse event, the topical corticosteroid used was ophthalmic
or otic, the report described a congenital anomaly in a neonate born to an
adult woman who had used topical corticosteroids during pregnancy, the report
described obvious misuse of a topical corticosteroid (e.g., a 3-year-old child
using Lotrisone cream as toothpaste), or a legible copy of the report was not
available. We included the 202 remaining reports in this review.
SUMMARY OF CASES
The
characteristics of the 202 cases in the series are presented below.
|
Age: (n=199) |
Mean
7.7 yrs, median 7 yrs (range, 8 days to 18 years) |
|
Gender: |
Male-78, female-111, not specified-13
|
|
Time
to onset: |
Mean
169.3 days, median 30 days (range, 1 day to 7 years) |
|
Location: |
US-184, non-US-14, unk-4
|
|
Report
year: |
1970-2 1971-5 1973-1 1975-3 1976-1 1977-2 1978-1 1979-1 |
1980-3 1982-1 1983-6 1984-5 1985-8 1986-6 1987-14 1988-11 1989-5 |
1990-26 1991-4 1992-16 1993-15 1994-12 1995-18 1996-10 1997-13 1998-6 1999-3 |
2000-3 2001-1 |
Event: Local
irritation, application site reaction-66
Lack of effect-32
Skin depigmentation or
discoloration-30
Striae or skin atrophy-30
Cushing’s syndrome-6
Growth retardation-5
Hyperglycemia, diabetes-5
Scarring or disfigurement-5
Staphylococcal infection (new or worsened), folliculitis, furunculosis, staph scalded skin syndrome-5
Genital hypertrichosis-4
Hirsutism-4
Rosacea-4
Acne-3
Glaucoma-3
Immediate hypersensitivity-3
Adrenal insufficiency-2
Bruising-2
Fungal infection-2
Gynecomastia-2
Lesions, unspecified-2
Immunodeficiency and PCP-2
Mental status or mood change-2
Perioral dermatitis-2
Seizure-2
Others (1 case each):
alopecia,
amenorrhea, asthenia, asthma exacerbation, deafness, delayed puberty,
dizziness, dyspepsia, granulomatous
lesion, hypertonia, idiopathic thrombocytopenic purpura, myasthenia, obesity,
perforated duodenal ulcer, pseudotumor cerebri, shortness of breath, skin cancer,
underdeveloped breasts, underdeveloped penis, urinary tract infection, vaginal
bleeding
(more than 1 event per case possible)
Indication: Eczema-36
Tinea-24
Diaper
rash-21
Unspecified
rash-19
Atopic
dermatitis-12
Psoriasis-12
Dermatitis-9
Unspecified
fungal infection-6
Poison
ivy-5
Alopecia-4
Seborrhea-4
Others
(reported in fewer than 4 cases)-
Abrasions,
acne, allergic contact dermatitis, anal fissure, chemical burn, dry red scale,
eosinophilia pustular folliculitis, erythema, granuloma annulare, heat rash,
hypertrophic scars, icthyosis, inflammation of finger, insect bite, keloids,
keratosis pilaris, Leiner’s disease, mastocytosis, mosquito bite, necrobiasis
lipoidica dibeticorum, patches of red skin, red scaly plaque, saliva rash,
scabies pruritus, staph infection, scar from laceration, vitiligo
(indication
for use of topical steroid not stated in 21 cases)
|
Drugs and dosage forms implicated More
than one product was implicated in some cases; the strength of the product
used was not reported in most cases. |
|
|
Alclometasone
dipropionate cream—5 ointment—1 dosage form not stated—1 Amcinonide
cream—3 dosage form not stated—2 Betamethasone
dipropionate cream—6 cream, augmented—7 gel—1 lotion—1 ointment—5 Betamethasone
and neomycin cream—1 Betamethasone
valerate cream—2 ointment—1 Betamethasone
valerate and gentamicin ointment—3 Betamethasone dipropionate
and clotrimazole cream—52 Clobetasol
propionate cream—7 ointment—4 lotion—1 Clocortolone pivalate cream—1 Desonide
cream—1 Desoximetasone cream—6 gel—1 dosage form not stated—3 Dexamethasone
and neomycin cream—1 |
Diflorasone
diacetate ointment—2 Fluocinolone
acetonide cream—8 solution—1 dosage form not stated—2 Fluocinonide
cream—3 ointment—1 Flurandrenolide
cream—1 tape—2 Fluticasone
propionate cream—4 ointment—1 Halcinonide cream—2Halobetasol
propionate cream—1 Hydrocortisone
cream—5 lotion—1 ointment—2 Hydrocortisone
valerate cream—11 ointment—1 Hydrocortisone
and clioquinol—2 Mometasone
furoate monohydrate cream—15 lotion—6 ointment—5 Triamcinolone
acetonide
cream—3 ointment—1 Triamcinolone
acetonide and nystatin cream—18 |
Buttocks/groin/genitals
(including “diaper area”)-32
Legs/feet-22
Arms/hands-19
Head/scalp-12
Trunk-8
“Entire
body”-4
Axilla-2
Periocular-2
Not
stated-79
Disability-5
Hospitalization-14
Life threatening-1
(outcome not stated in most cases)
Seventy-eight
male children, 111 female children, and 13 children of unspecified gender
experienced adverse events after receiving topical corticosteroids. The
patients ranged in age from 8 days to 18 years with a mean age of 7.7 years.
Sixty-five (32.2%) of the adverse events occurred in pediatric patients younger
than 3 years of age, and 32 (15.8%) events occurred in infants. One hundred
forty (69.3%) of the adverse events occurred in patients younger than 12 years
of age. The patients in the case series had received topical corticosteroids
for 1 day to 7 years before experiencing the adverse event. The median time to
onset was 30 days. In 40 cases, application of topical corticosteroids
continued for 90 days or longer, and in 17 cases application of topical
corticosteroids continued for over a year.
Betamethasone-containing
products were the most frequently implicated in reports of adverse reactions
(79, 39%). Betamethasone dipropionate and clotrimazole cream was implicated in
52 (25.7%) reports, more than any other product. The most commonly reported
events were local irritation and application site reactions (66), lack of
effect (32), skin depigmentation or discoloration (30), and skin striae or
atrophy (30). Outcome was not reported in most cases; however, serious outcomes
(death-1, disability-5, hospitalization-14, life threatening-1) were reported.
The most common indications for use were eczema (36), tinea infections (24),
diaper rash (21), unspecified rash (19), atopic dermatitis (12), and psoriasis
(12). The products were applied most often to the face and/or neck (40) or to
the buttocks, groin, and/or genital area (32). Positive dechallenge was
reported in 21 cases and positive rechallenge was reported in three cases. The
area of application was occluded in five cases, and covering (but not
occlusion) with “Kling wrap” was reported in one case. In many cases in which
occlusion was not reported, partial occlusion might have occurred with clothing
or a diaper.
In
some cases topical corticosteroids were continued for extended periods of time
in high-risk settings. Twenty-two patients younger than 4 years of age received
topical corticosteroids for longer than 4 weeks. Seven of these patients
received the drugs for longer than 6 months. Fifteen patients had topical corticosteroids
applied to their groin/genitals (including
“diaper area”) longer than 4 weeks. Four of these patients received the drugs
for longer than 6 months.
Sometimes
topical corticosteroids were continued despite the failure of the treatment.
The reports do not explain why the topical corticosteroids were continued when
they were not effective. In twelve of the cases in the series, topical
corticosteroids were continued for longer than 4 weeks even though the
dermatoses did not improve. In one case the topical corticosteroid was
continued for one year despite “lack of effect.”
Two
cases from the series are presented below.
AERS
5209109, MFR A0006921, US (NY) 1995
A
registered nurse reported that her 9-year-old daughter received fluticasone
cream for several weeks to treat an unspecified rash. After several weeks, the
child developed fatigue, polydipsia, polyuria, glycosuria, and hypergylcemia.
She was diagnosed with insulin-dependent diabetes. Fluticasone was discontinued
and the child was treated with insulin.
AERS 1000000771, MFR 97100307, US (CO) 1997
A
dermatologist reported that a 21-month-old girl received betamethasone
dipropionate and clotrimazole cream twice daily almost since birth to treat
diaper rash. Examination by the dermatologist noted folliculitis around the
neck, and epidermal atrophy, hypopigmentation and telangiectasis in the
perineal area, mons pubis, and inguinal creases. Betamethasone dipropionate and
clotrimazole cream was discontinued, and the diaper rash was treated with a cream
not containing corticosteroid (Desitin®). The folliculitis was treated with
ketoconazole. The child’s condition was improving at the time of the report.
A subset of eleven pediatric patients experienced adrenal insufficiency (2), Cushing’s syndrome (7), and/or growth retardation (5) after receiving topical corticosteroids. A listing of these cases is presented in Attachment 2. These patients ranged from 5 months to 15 years of age. Two patients each used betamethasone valerate cream, clobetasol propionate cream, and mometasone ointment. The following other topical corticosteroids were cited in one report each:
betamethasone
ointment;
betamethasone
dipropionate and clotrimazole cream;
betamethasone
and neomycin cream;
clobetasol
propionate scalp lotion;
flumetasone
pivalate;
fluocinonide
cream;
flurandrenolide
tape;
mometasone
cream; and
triamcinolone
cream.
In
four cases the patients used more than one topical corticosteroid product. The
topical corticosteroid was used for a median of 300 (range, 22 to 1825) days.
In two cases each the children received topical corticosteroids to treat diaper
rash and eczema. Other diagnoses for the use of topical corticosteroids
included alopecia, icthyosis, Leiner's disease, psoriasis, treatment of a scar,
and unspecified patches of red skin. Five patients were hospitalized, and one
patient with Cushing’s syndrome died of a respiratory infection.
Two
cases are presented below.
AERS 4918014, MFR 9207239, Maylasia 1992 (literature report)
A
6-week-old infant with icthyosis was treated intermittently with betamethasone
cream for 4 weeks. The product used was not specified. The baby was
hospitalized with severe dyspnea, generalized edema, Cushingoid features, and
heart failure. The infant initially responded to unspecified treatment, but
eventually died of a respiratory system infection.
AERS 5231157, MFR 9409043, US (FL) 1994
A
2-year-old girl with atopic dermatitis was prescribed mometasone furoate
ointment. Treatment with the ointment continued for the next 4 years. A
physician reported the 6-year-old child experienced growth retardation.
CONCLUSION/RECOMMENDATION
We
reviewed 202 AERS adverse events for the topical corticosteroids reported for
pediatric patients age 0 to 18 years of age. Local irritation and application
site reactions were the most frequently reported events in pediatric patients.
Numerous systemic adverse events were reported, including striae, Cushing’s
syndrome, growth retardation, hyperglycemia, hirsutism, glaucoma, and adrenal
insufficiency. Some cases resulted in serious outcomes, including
hospitalization and death. Long-term application of topical corticosteroids in
high-risk settings (for example, application to the genital and groin area in
very young patients) resulted in numerous adverse events. In some cases topical
corticosteroids were continued despite treatment failure.
We
recommend that the systemic adverse events in the AERS database be included in
the labeling for these products. Additionally, the labeling of each product
should advise practitioners of the appropriate duration of use of the product.
The labeling should give information regarding how quickly improvement in
dermatoses should occur after therapy with a topical corticosteroid is started,
and practitioners should be advised to discontinue the product if improvement
does not occur within this timeframe.
References
1. Ellison, JA,
Patel L, Ray D, et al. Hypothalamic-pituitary-adrenal
function and glucocorticoid sensitivity in atopic dermatitis. Pediatrics 2000;
105(4): 794-799.
2. Turpeinen M. Adrenocortical response to
adrenocorticotropic hormone in relation to duration of topical therapy and
percutaneous absorption of hydrocortisone in children with dermatitis. Eur J
Pediatr 1989; 148(8): 729-31.
3. Turpeinen M, Salo OP, Leisti S. Effect of percutaneous absorption of
hydrocortisone on adrenocortical responsiveness in infants with severe skin
disease. Br J Dermatol 1986; 115(4): 475-84.
4. Shaffer MP, Feldman SR, Fleischer AB Jr. Use of clotrimazole/betamethasone diproprionate by family physicians. Fam Med 2000; 32(8): 561-5.
.
|
Joyce
Weaver, Pharm.D., Safety Evaluator Concur: |
|
Claudia
B. Karwoski, Pharm.D., Team Leader |
|
Alclometasone
dipropionate products: (Aclovate ointment; NDA
018702—12/14/1982) (Aclovate cream; NDA 018707—12/14/1982) Amcinonide
products: (Cyclocort cream; NDA
018116—10/18/1979) (Cyclocort ointment; NDA
018498—11/13/1981) (Cyclocort lotion; NDA
019729—6/13/1988) Betamethasone dipropionate products: (Diprosone cream; NDA
017536—1/29/1975) (Diprosone ointment; NDA
017691—4/15/1976) (Diprosone lotion; NDA 017781—2/1/1977) (Diprosone aerosol; NDA 017829—5/24/1977) (Diprolene ointment; NDA
018741—7/27/1983) (Diprolene cream; NDA
019408—1/31/1986) (Diprolene AF cream; NDA
019555—4/27/1987) (Diprolene gel; NDA
019408—11/22/91) (Diprolene lotion; NDA 019716—8/1/1988) Betamethasone
dipropionate and clotrimazole products: (Lotrisone cream; NDA
018827—7/10/1984) (Lotrisone lotion; NDA
020010—12/8/2000) Betamethasone
valerate products: (Luxiq aerosol; NDA
020934—2/28/1999) Clobetasol
propionate products: (Temovate cream; NDA 019322—12/27/1985) (Temovate ointment; NDA
019323—12/27/1985) (Temovate solution; NDA
019966—2/22/1990) (Temovate gel; NDA
020337—4/29/1994) (Temovate E cream; NDA
020340—6/17/1994) (Olux foam; NDA 021142—5/26/2000) Clocortolone
pivalate products: (Cloderm cream; NDA
017765—8/22/1977) Desonide
products: (Tridesilon cream; NDA
017010—1/04/1972) (Tridesilon ointment; NDA
017426—11/1/1974) (Desowen cream; NDA
019048—12/14/1984) (Desowen lotion; NDA 072354—1/24/1992) (Desowen ointment; NDA 071425—6/15/1988) Desoximetasone
products: (Topicort cream; NDA
017856—2/28/1977) (Topicort LP cream; NDA
018309—3/28/1980) (Topicort gel; NDA
018586—3/29/1982) (Topicort ointment; NDA
018594—10/3/1983) (Topicort ointment; NDA
018763—9/30/1983) Dexamethasone
products: (Decaspray aerosol; NDA
012731—3/29/1961) Diflorasone
diacetate products: (Florone cream; NDA
017741—9/14/1977) (Florone ointment; NDA
017994—3/1/1978) (Florone E cream; NDA
019259—8/28/1985) (Psorcon E ointment; NDA
019260—8/28/1985) (Psorcon E cream; NDA 020205—11/20/1992) Fluocinolone
acetonide products: (FS Shampoo; NDA 020001—8/27/1990) (Synalar cream; NDA
012787—2/15/1963) (Synalar ointment; NDA
013960—6/19/1963) (Synalar solution; NDA
015296—5/27/1964) (Synalar-HP cream; NDA 016161—7/25/1967)
(Derma-smoothe FS oil; NDA
019452—2/3/1988) Fluocinonide
products: (Lidex cream; NDA
016908—6/30/1971) (Lidex ointment; NDA
016909—9/22/1971) (Lidex gel; NDA 017373—5/15/1973) (Lidex solution; NDA
018849—4/8/1984) Flurandrenolide
products: (Cordran ointment; NDA
012806—10/18/1965) (Cordran lotion; NDA 013790—3/19/1963) (Cordran tape; NDA 016455—7/29/1969) Fluticasone
propionate products: (Cutivate ointment; NDA
019957—12/14/1990) (Cutivate cream; NDA
019958—12/18/1990) Halcinonide
products: (Halog cream; NDA 017556—11/27/1974) (Halog solution; NDA
017823—5/4/1977) (Halog ointment; NDA
017824—6/15/1977) (Halog-E cream; NDA
018234—1/24/1980) Halobetasol
propionate products: (Ultravate cream; NDA
019967—12/27/1990) (Ultravate ointment; NDA
019968—12/17/1990) Hydrocortisone
products: (Cortef cream; NDA
009460—8/20/1954) (Cortef ointment; NDA
008917—7/28/1953) (Cortril ointment; NDA 009176—5/24/1972) Hydrocortisone
butyrate products: (Locoid cream; NDA
018514—3/31/1982) (Locoid ointment; NDA
018652—10/29/1982) (Locoid solution; NDA
019116—2/25/1987) (Locoid lipocream; NDA
020769—9/8/1997) Hydrocortisone
buteprate product: (Pandel cream; NDA
020453—2/28/1997) Hydrocortisone
valerate products: (Westcort cream; NDA 017950—before 1/1/1982) (Westcort ointment; NDA 018726—8/8/1983) Methylprednisolone
acetate products: (Medrol acetate ointment; NDA
012421—6/21/1960) Mometasone
furoate monohydrate (Elocon cream; NDA
019625—5/6/1987) (Elocon lotion; NDA 019796—3/30/1989) (Elocon ointment; NDA
019543—4/30/1987) Prednicarbate
products: (Dermatop cream; NDA
019568—9/23/1991) (Dermatop emollient cream; NDA
020279—10/29/1993) Triamcinolone
acetonide products: (Kenalog ointment; NDA
011600—6/17/1977) (Kenalog cream; NDA
011601—11/13/1978) (Kenalog spray; NDA
012104—10/11/1974) (Kenalog orabase ointment; NDA
012097—3/4/1960) |
|
Mfr report # |
Loca-tion |
yr |
Age (yrs) |
Gender |
Drug and dose |
application site |
duration (days) |
indication |
AE |
Outcome |
comment |
|
B0104663A |
France |
2001 |
15 |
M |
clobetasol propionate cream (Dermaval) 10 - 20 mg/d |
|
45 |
psoriasis |
Depigmentation, striae, possible adrenal insufficiency |
HO |
Positive dechallenge |
|
97-10-8020 |
AUS |
1997 |
14 |
M |
mometasone ointment (Elocon) 15 g Q2-3 days & betamethasone ointment 30 g Q 7-10 days |
entire body |
|
eczema |
adrenal insufficiency, delayed puberty, growth
suppression |
|
bone scan showed 2-3 yr growth delay; prednisolone cc
med |
|
B0042474 |
Japan |
1996 |
10 |
F |
flumetasone pivalate clobetasol, propionate
(Dermovate) |
Scalp |
180 |
|
Cushing’s syndrome, obesity, inc hair growth, acne |
HO |
|
|
95-08-0174 |
US (NJ) |
1995 |
3 |
M |
fluocinonide, triamcinolone, mometasone cream (Elocon) |
|
455 |
patches of red skin |
growth retardation, leukoderma |
|
Digoxon and furosemide cc meds |
|
94-10-0184 |
US (CO) |
1994 |
1.25 |
M |
betamethasone and clotrimazole cream (Lotrisone) |
diaper area |
120 |
diaper rash |
growth retardation |
|
|
|
94-09-043 |
US (FL) |
1994 |
6 |
F |
mometasone furoate ointment (Elocon) |
|
1460 |
atopic dermatitis |
growth retardation |
|
|
|
92-09-024 |
US (MD) |
1992 |
9 |
F |
betamethasone valerate cream (Valisone) |
|
1825 |
eczema |
growth retardation |
|
|
|
92-07-239 |
May-lasia |
1992 |
0.12 |
M |
betamethasone valerate cream |
|
28 |
icthyosis |
Cushing’s syndrome |
DE |
1 m/o infant; DE due to respiratory infection |
|
92-05-178 |
France |
1992 |
0.67 |
M |
neomycin &
betamethasone cream (Diprosone) 1.5 mg betamethasone/day |
scalp, diaper area |
180 |
Leiner's disease |
Cushing’s syndrome |
DS, HO |
8 m/o baby; residual retardation |
|
US91070727A |
US (TX) |
1991 |
14 |
F |
flurandrenolide tape (Cordran tape) |
inner thigh |
22 |
Tx scar from repair of laceration |
Disfigurement, Cushing’s syndrome |
HO |
|
|
G0003711 |
Hong Kong |
1990 |
0.42 |
M |
clobetasol propionate cream (Temovate) 1.78 g/ day |
diaper area |
300 |
diaper rash |
Cushing’s syndrome |
HO |
5 m/o baby given 1 tube (25 g) every 2 weeks for 10
months; positive dechallenge |