acne and approaches to pharmacotherapy involving acne

1. ACNE

2. DEFINITION-
Acne is a chronic, multifactorial,
self limited, disease of the pilocebaceous
unit . extremely common during
adolescence and early adult life. Acne are
pleomorphic , resulting with a variety of
lesions consisting of comedones, papules,
pustules, nodules and on sequelae to
active lesion –pitted or hypertrophic scars.

3. EPIDEMMIOLOGY
Acne is so common that it often has been termed as physiologic .
Mild degre of acne are often seen at birth, and mild cases may
continue tin the neonatal period
Acne is often an early menifestation of puberty.
Man affected earliar and more severely than womens
In girls the occurance ofacne may precede menarcheby more than a
year .
More common in the middle to late teenage period (13—19 years)
subsequently the incidence decreases.
Particularly in womenacne may persist through third decade or even
later .
Acne seems to be familial
Nodulocystic(acne conglobata) has been reported to be more common
in white males than in black
Acne is more severe having chromosomal keriotype XYY.

4. PATHOLOGY
Acne developes in sebacious follicles and the primary lesion is the comedo.
Comedo development starts in the midportion of the follicle as an expanding
mass of lipid impregnated keratinous material; resulting in thining and balloning
out of follicular wall.gradually more keratinous metarial accummulates and
further thinning and dilatation of the follicular wall occure .
At the same time sebocious gland begins to atropy and are replaced by
undifferentiated epithelial cells. Open comedo has a patulous orifice and the
keratinous material is arranged in a lemellar concentric fasion. Close comedo
differs from the open comedo in that the keratious material is not as compact
and the folliclar orifice is narrow and not distended.
Fully developed open comedo is not ussually the site of inflammatory
changes,unless it is tramatized by the patient . the initial event appears to be
escape of lipids through an oedematous comedo wall. With the developed of
cellular reaction in the adjacent dermis.
Once complete rupture occurred the entire contents of the comedo are extruded
into the dermis , this reaction is much greter and giant cells are
common,reflecting the escape of the keratinous materials. these ruptured
lesions appears as a pastules, a nodules or as a nodule surrounded by pastules.
Further rupture may occure leading to multy channeled tract as can be seen in
many acne scars. Fibrous contraction also contribute to scar formation.

5. ETIOLOGY
Although the basic case is unknown. There is considerable information on
the various factors concerned in this pathogenesis are-
an alteration in the pattern of keratinization within the follicle
increase sebum secretion by the sebousious gland
essential fatty acid defficiency syndrome
predominent organism/follicular flora
anaerobic pleomorphic diptheroid –
PROPIONIBACTERIUM ACNE(c-acne-type-1)
PROPIONIBACTERIUM GRANULOSUM (c-acne-type-2)
The yeast PITYROSPORUM OVALE
COAGULASE NEGATIVE MICROCOCCI also found.
andrrogen in the pathogenesis of acne
some drugs may causes acne form lesion
many patients reports that their acne flares during periods of any kinds of
stress. Although objective data are limited , stress is known to increase
the output of adrenal steroids.

7. Clinical feature:
The primary site of acne is the face and to a lesser degree the back, chest and
shoulders on the trunk lesions tend to be numerous near the midline.
The lesions may be either non inflammatory or inflammatory.
The non inflammatory lesions are comedons which may be either open (black heads)
or closed (white heads).
The open comedo appears as a flat or slightly raised lesion with a central dark
co;ored follicular impaction of keratin and lipid.
The close comedones may be difficult to visualize. They apear as pale, slightly
elevated, small papules,and do not have a clinically visible orifice . closed
comedones are potential precursors for the large inflammatory lesions
Although comedons are the primary lesions of acne, they are not unique in this
disease as they may be seen under other conditions(senile comedones which are
common ,perticularly in periorbital area of older persons ,and in atropic skin resulting
from x-ray therapy ).
The inflammatory lesions vary from small papules with an inflammatory areola or
pustules to large ,tender,fluctuant nodules .some of the large nodules previously
known as custs and the term nodulocystic has been used to describe severe case of
inflammatory acne . whether the lesion appears as a papule, pustule, or nodules
depends on the extentand location of the inflammatory infiltrate in the dermis.

11. VARIANTS OF ACNE :
various minor subgroups on the basis of
the predominant lesions

12. Neonatal acne:
An acne form erruption may occure in
neoborn or infants . this is often seen in
the nose and adjacent portion of the
cheeks .probably related to the glandular
development that occures in fetal life due
to transplacental stimulation of adrenals .
acne can also start after birth and persist
for few months.

13. Helogen acne:
Iodides and bromides may induce an
acneform erruption . the iodine contents of
iodised salt is low and therefore ,it is
extremely unlikely that enough iodised salt
could be ingested to cause this type of
acne. It is due to ingestion of halogen
containing sedatives and expectorance.

14. Occupational acne:
Several different groups of industrial
compounds may cause acne. these include
coltar derivative , insoluble cutting oil ,and
chlorinated hydrocarbons . these tends to be
quite inflammatory and in addition to large
comedons is characterized by papules, pustules,
large nodules and true cysts , tar acne is often
accompained by hyper pigmentation .the lesions
of industrial acne are not restricted to the face,
are more common on covered areas where
intimate contact of clothing present.

15. Acne cosmetica:
Various cosmetic compounds were found
to induce comedo formation .and
cosmetics are considered to be a major
cause of adult acne in women. Therefore
with the exception of very greasy ,
occlusive products, cosmetics are
infrequent etiologic agents for acne.

16. Pomade acne:
Pomades are comedogenic . This form of
acne is seen almost exclusively in black
males. Characterized by multiple closely
packed comedones close to the hairline. It
may can spread over the face , extensively
on the cheek.

17. Acne detergicans:
The occurrence of papular and comedonal
acne in compulsive washers due to
excessive use of detergents.

18. Acne mechanica:
Acneform erruption may occurs after repetitive
physical trauma to the skin such as rubbing. This
can occurs from clothing (belts and straps) or
sports equipements(football helmets and
shoulder pads) . it has been induced by
occluding the skin with adhesive tape and
produce flares of preexisting acne .it is
commonly occurs in forehead, chin and
shoulder .

19. Acne with Facial Edema:
Acne may uncommonly be associated with
a peculiar inflammatory edema of the mid
third of the face. The edema is
unresponsive to high dose oral antibiotics
but sometimes responds to oral
glucocorticoids, often in combination with
isotretinoin. However reccurance are
common when steroids are stopped.

20. Tropical acne:
Acne vulgaris may flare and a severe folliculitis
may develop in tropical climates. These skin
conditions have been a major cause of
dermatologic disability in the armed forces.
These occurs mainly in on the trunk and
buttocks, has many deep large inflammatory
nodules with multiple draining areas. Exact
pathogenesis is unknown, although secondary
infection with coagulase positive staphylococci
almost always ensures. Systemic antibiotics
must be given, but often more important is the
necessity to remove the patient to a cooler
environment.

21. Acne aestivalis:
This monomorphous eruption consists of
multiple uniform red papular lesions and
has been reported to occur after sun
exposure. Common in Scandinavian
woman after the have been southern
Europe, Mainly 20 to 30 years. The lesions
are common on shoulders, arms, neck and
chest.

22. Acne Conglobata:
This is a highly inflammatory disease with
comedones, papules, pastuls, nodules,
abscesses and draining sinus tracts on the back,
buttocks, chest and to a lesser extent on the
abdomen, shoulders, neck, face, uppar arms
and thighs. Healing occurs with severe scarring,
which is often keloidal in nature. The
inflammatory lesions are large, tender, dusky
colored. The draining lesions discharge a foul
smelling serous, purulent or mucoid materials.
This type of acne is rare and usually starts in
adult life. Males are predominates than females.

23. Acne Fulminans:
This catastrophic disease has also been called acute
febrile ulcerative acne. It is characterized by the sudden
appearance of massive inflammatory tender lesions of
the back and chest that rapidly become ulcerative and
heal with scarring. It is exclusively common in teenage
boys, the face is often not involved. The patients are
febrile, have a leukocytosis of 10000 to 30000/ mm 3.
Usually have poly arthalgia, myalgia and other systemic
symptoms. X-Ray examination may disclose the
presents of osteolytic areas in parts of bone tenderness.
The face is not involved as frequently and the neck is
usually spared, ulcerative and crusted lesions are
unique.

24. Drug acne:
Following administration of glucocorticoids or
corticotropin, a folliculitis may appear. This is very
uncommon in children but may occur in any adult as
early as 2 weeks after steroids are started. Similar
lesions may follow the prolonged applications of tropical
glucocorticoids or corticotropin to the face. This type of
acne clearly defers form acne vulgaris in its distributions
and in the type of lesions observed. Post inflammatory
hyper pigmentation may occur but comedones, cysts,
and scarring are unusual.

25. INVESTIAGATION
In general laboratory tests is not indicated for patients with acne unless hyperandrogenism is
suspected. Excess endrogens may be produced by adrenal gland or ovary.
1. Tests to exclude hyperandrogenism:
Serum DHEAS
Total testosterone
Free testosterone
LH and FSH ratio
Testing should be obtained in the luteal face of the menstrual cycle (with in 2 weeks prior to the
onset of the means).
Patients on orsal contraceptives will need to discontinue their medication at least 1 month prior
to testing.
2. Congenital adrenal hyperplasia
Serum DHEAS level= range is 4000 – 8000 ng/ml.
3. Adrenal tumor
Serum DHEAS level= 8000 ng/ml.
4. Polycystic ovary disease
Serum total testosterone level= range is 150 – 200 ng/dl.
LH and FHS ratio= 2.0
5. Ovarian tumor
Serum total testosterone level= 150 ng/dl.

26. Treatment
according to type of the lesion of acne:

27. Comedonal Lesions
Prescribe one of the followings:
Topical retinoid
Azelaic acid
Salicylic acid
If results are unsatisfectory,
increase strength
or change medication

28. Mixed comedonal lesions
and papulopustules.
Prescribe one of the followings:
Retinoid + topical antibiotic
Retinoid + benzoyl peroxide
Retinoid + benzoyl peroxide + topical antibiotic
Azelaic acid + benzoyl peroxide
Azelaic acid + topical antibiotic
If results are unsatisfactory
prescribe retinoid + course of oral antibiotic.

29. Papules and pustules
Prescribe Benzoyl peroxide
If results are unsatisfactory,
switch to or add topical antibiotic
If results are unsatisfactory
add course of oral antibiotic.

30. Cystic lesions
Prescribe course of
oral antibiotic + mixed comedonal
papulopustular topical therapy.
If results are unsatisfactory,
consider wheather patient is a
candidate for oral isotretinoin therapy.
If results are unsatisfactory
consider possibility of endocrinopathy
If endocrinopathy
is identified, Treat.
If no sign of endocrinopathy
is found, consider repeat
course of oral isotretinoin

31. Drugs use in Acne

32. Antibiotics……

33. Drug Name- Doxycycline
Description- Antibacterial agent effective against gram-positive and gram-
negative organisms. Available in 20-, 50-, and 100-mg
preparations.
Adult Dose- 100 mg PO bid
Pediatric Dose- <8 years: Not recommended
>8 years: 2-5 mg/kg/d PO/IV in 1-2 divided doses; not
to exceed 200 mg/d
Contraindications- Documented hypersensitivity; severe hepatic
dysfunction
Interactions- Bioavailability decreases with antacids containing
aluminum, calcium, magnesium, iron, or bismuth
subsalicylate; tetracyclines can increase hypoprothrombinemic effects of
anticoagulants; tetracyclines can decrease effects of oral contraceptives,
causing breakthrough bleeding and increased risk of pregnancy
Pregnancy- D - Fetal risk shown in humans; use only if benefits
outweigh risk to fetus
Precautions- Photosensitivity may occur with prolonged exposure to
sunlight or tanning equipment; reduce dose in renal
impairment; consider drug serum level determinations
in prolonged therapy; tetracycline use during tooth development (last one
half of pregnancy through age 8 y) can cause permanent discoloration of
teeth; Fanconilike syndrome may occur with outdated tetracyclines

34. Drug Name- Tetracycline
Description- Antibacterial agent effective against gram-positive and
gram-negative organisms.
Adult Dose- 250-500 mg PO q6h
Pediatric Dose- <8 years: Not recommended
>8 years: 25-50 mg/kg/d (10-20 mg/lb) PO divided qid
Contraindications- Documented hypersensitivity
Interactions- Bioavailability decreases with antacids containing
aluminum, calcium, magnesium, iron, or bismuth
subsalicylate; can decrease effects of oral
contraceptives, causing breakthrough bleeding and increased risk of
pregnancy; tetracyclines can increase hypoprothrombinemic effects of
anticoagulants
Pregnancy- D - Fetal risk shown in humans; use only if benefits
outweigh risk to fetus
Precautions- Photosensitivity may occur with prolonged exposure
to sunlight or tanning equipment; reduce dose in renal
impairment; consider drug serum level determinations
in prolonged therapy; tetracycline use during tooth development (last one
half of pregnancy through age 8 y) can cause permanent discoloration of
teeth; Fanconilike syndrome may occur with outdated tetracycline

35. Drug Name- Minocycline
Description- Treats infections caused by susceptible gram-negative
and gram-positive organisms, in addition to infections
caused by susceptible chlamydial, rickettsial, and mycoplasmal organisms.
Available in 50-, 75-, and 100-mg preparations.
Adult Dose- 50-100 mg PO bid
Pediatric Dose- <8 years: Not recommended
>8 years: 4 mg/kg PO initially, followed 2 mg/kg q12h
Contraindications- Documented hypersensitivity; severe hepatic
dysfunction
Interactions- Bioavailability decreases with antacids containing
aluminum, calcium, magnesium, iron, or bismuth
subsalicylate; can decrease effects of oral
contraceptives, causing breakthrough bleeding and increased risk of
pregnancy; tetracyclines can increase hypoprothrombinemic effects of
anticoagulants
Pregnancy- D - Fetal risk shown in humans; use only if benefits
outweigh risk to fetus
Precautions- Photosensitivity may occur with prolonged exposure to
sunlight or tanning equipment; reduce dose in renal impairment; consider
drug serum level determinations in prolonged therapy; tetracycline use
during tooth development (last one half of pregnancy through age 8 y) can
cause permanent discoloration of teeth; Fanconilike syndrome may occur
with outdated tetracyclines; hepatitis or lupuslike syndromes may occur

36. Drug Name- Trimethoprim/sulfamethoxazole
Description- Antibiotic with activity against many gram-positive and
gram-negative organisms. Inhibits bacterial growth by
inhibiting synthesis of dihydrofolic acid. Available as 80
mg trimethoprim and 400 mg sulfamethoxazole or as 160 mg trimethoprim
and 800 mg sulfamethoxazole (double strength).
Adult Dose- 160 mg TMP/800 mg SMZ PO q12h
Pediatric Dose- 8 mg/kg/d TMP/40 mg/kg/d SMZ PO/IV divided q12h
Contraindications- Documented hypersensitivity; megaloblastic anemia
due to folate deficiency
Interactions- May increase PT when used with warfarin (perform
coagulation tests and adjust dose accordingly);
coadministration with dapsone may increase blood
levels of both drugs; coadministration of diuretics
increases incidence of thrombocytopenia purpura in
elderly persons; phenytoin levels may increase with coadministration; may
potentiate effects of methotrexate in bone marrow depression; hypoglycemic
response to sulfonylureas may increase with coadministration; may increase
levels of zidovudine
Pregnancy- C - Fetal risk revealed in studies in animals but not
established or not studied in humans; may use if
benefits outweigh risk to fetus

37. Retinoids…..
(vitamin A derivatives)

38. Classification of Retinoids
1st Generation..
-Tretinoin
2nd Generation..
-Isotretinoin
-Etretinate
3rd Generation..
-Adapalene
-Tezarotene
4th Generation..
-Bexarotene

39. Drug Name- Isotretinoin (Accutane)
Description- Most effective oral medication. Oral agent that treats
serious dermatologic conditions. Isotretinoin is
synthetic 13-cis isomer of naturally occurring tretinoin
(trans-retinoic acid). Both agents are structurally related to vitamin A.
Decreases sebaceous gland size and sebum production. May inhibit
sebaceous gland differentiation and abnormal keratinization.
(Female patients must sign an informed consent that they will use
contraceptives during the treatment course and for 30 d after discontinuing
therapy)
Adult Dose- Total cumulative dose of 120-150 mg/kg
recommended; starting dose should be <0.5 mg/kg/d
PO; dose may be increased to 1 mg/kg/d as tolerated
Pediatric Dose- Not established
Contraindications- Documented hypersensitivity
Interactions- Toxicity may occur with vitamin A coadministration;
pseudotumor cerebri or papilledema may occur when coadministered with
tetracyclines; may reduce plasma levels of carbamazepine
Pregnancy- X - Contraindicated; benefit does not outweigh risk
Precautions- Obtain 2 negative pregnancy test results in patients of
childbearing potential prior to initiating therapy; pregnancy must be avoided
during and for 1 mo after treatment, and monthly pregnancy test results must
be documented; hyperlipidemia may develop; pseudotumor cerebri, vision
impairment, headaches, myalgias, arthralgias, and depression have been
reported; dry skin and cheilitis are nearly universal adverse effects

40. Drug Name- Tretinoin
Description- Inhibits microcomedo formation. Normalizes
follicular epidermal differentiation and exhibits
anti-inflammatory properties. Available as
0.025%, 0.05%, and 0.1% creams. Also
available as 0.01% and 0.025% gels.
Adult Dose- Begin with lowest tretinoin formulation and
increase as tolerated; apply evening; lower
frequency of application if irritation develops
Pediatric Dose- <12 years: Not established
>12 years: Apply as in adults
Contraindications-Documented hypersensitivity
Interactions- Coadministration with benzoyl peroxide may
lessen effectiveness
Pregnancy- C - Fetal risk revealed in studies in animals
but not established or not studied in humans;
may use if benefits outweigh risk to fetus
Precautions- Photosensitivity may occur with excessive
sunlight exposure; erythema and peeling may
occur (most prominent within first few wk of
treatment)

41. Drug Name- Adapalene
Description- A naphthoic acid derivative that binds the
retinoic acid receptor. Normalizes follicular
epidermal differentiation and exhibits anti-
inflammatory properties. Available in cream,
gel, solution, and pledget formulations.
Adult Dose- Apply a small amount to involved skin qd
Pediatric Dose- Not established
Contraindications-Documented hypersensitivity
Interactions- None reported
Pregnancy- C - Fetal risk revealed in studies in animals
but not established or not studied in humans;
may use if benefits outweigh risk to fetus
Precautions- Erythema and peeling may occur in some
individuals; avoid contact with mucous
membranes, eyes, mouth, and nostrils; avoid
exposure to sunlight and sunlamps; dryness
of skin, scaling, erythema, burning, and pruritus may occur

42. Drug Name- Tazarotene
Description- Retinoid prodrug whose active metabolite
modulates differentiation and proliferation of
epithelial tissue; may also have anti-
inflammatory and immunomodulatory
properties. Available in 0.05% and 0.1%
cream and gel formulations.
Adult Dose- Apply sparingly to affected area qd
Pediatric Dose- Children: Not established
Adolescents: Administer as in adults
Contraindications-Documented hypersensitivity
Interactions- Do not use concomitantly with dermatologic
drugs or cosmetics that have a strong drying
effect on the skin (eg, salicylic acid, benzoyl
peroxide, astringents)
Pregnancy- X - Contraindicated; benefit does not
outweigh risk
Precautions- Erythema and peeling may occur at
application site