ACNE VULGARIS

AND ACNEIFORM ERUPTION

F I T Z PAT R I C K S I N G E N E R A L M E D I C I N E P G
1264
INTRODUCTION

• a self-limited disorder of the pilosebaceous unit that is seen primarily in adolescents

• present with a pleomorphic array of lesions, consisting of comedones, papules, pustules,
and nodules with varying extent and severity.
• due to genetic factors and environmental factors
PATHOGENESIS OF ACNE

• There are four steps have been identified:

1. Follicular epidermal hyperproliferation
2. Excessive production of sebum
3. Presense and activity of Propiniobacterium
acnes (now Cutibacterium acnes) normal
flora of pilosebaceous gland
4. Inflammation after the rupture of the
follicular wall lymphocytes (CD4 and 8)
predominance in first 24 hours 1-2days
neutrophils become more predominat
CONTINUES..

• Hyperproliferation of infundibulum keratinocytes and increase cohession between

keratinocytes plug in the infunfibulum ostiummicrocomedo occlusion of sebum, keratin,
dead cell and bacteria
• Several factors stimulate keratinocytes proliferation: Androgen (DHT) stimulation, decrease of
linoleic acid, C. Acne activity, and Interleukin-1 (IL-1)
• Linoleic acid is a essensial fatty acid long chain unsaturated, which level decrease in patient
with acne
• FGFR (fibroblast growth factor receptor) mutation  increase acne in apert syndrome 
increase IL-1 and 5a reductase increase proliferation of infundibulum keratinocytes
PATHWAY OF ANDROGEN METABOLISM

DHEAS (dehydroepiandrosteron) is a weak androgen produced by adrenal gland which

is converted to be a stronger DHT (dihidroxytestosteron) by the help of several
enzymes.
DHT induce keratinocytes proliferation and also stimulate cebocytes activity
SEBUM IN ACNES

• Patient with acnes produce MORE SEBUM than subject without acne but with the sam
QUALITY SEBUM
• Component of sebum  Triglyceride and lipoperoxides
• TG broken down into FFA by P.acne promote more bacteria to come
• Lipoperoxides also produce proinflammatory cytokins and activate PPAR (Peroxisome
proliferator activated receptor pathway
increase sebum furthermore
ESTROGEN ON ACNE

• Dosage need to decrease sebum production is greater than the amount of estrogen need to
inhibit ovulation?
• The action by directly opposing the effects of androgen within the sebaceous glands, negative
feedback loop decrease androgen production by pituitary gonadothropine release; directly
supress the sebaceous gland size and activity
STRESS ON ACNE

• In response to stress, CRH (corticotrophin releasing hormone) is released by the

hypothalamus whose reseptor present in cebocytes and keratinocytes upregulating their
activity increase sebum
• Increase in adrenal cortisol  increase sebum production and keratinocytes proliferation
P ACNES

• Gram positive, Rod Shape

• Anaerobic, Microaerobic ???
• Found normally in sebaceous follicles
• P acnes cell wall contain antigen that stimulate
antibody development initiating pro-
inflammatory events; also eliciting a delayed
hypersensitivity response
• Stimulating Toll like receptor (TLR-2) on
monocytes and PMN release pro inflammatory
cytokins of IL-1a, IL-8, IL-12, TNF-a,
CONTINUES..
DIET ON ACNE
• High glicemic index,dairy food, egg, meat increase IGF-1 increase androgen

Dietary factors increase the levels

of IGF1 synthesized from liver.
IGF1-mediated increased signaling
of androgen receptor results in
increased expression of FGF7 and
FGF10, the ligands of FGFR2b
signaling in keratinocyte. Both the
IGF1R and FGFR2b activation
results in a common downstream
pathway via activation of PI3/Akt,
MAPK, and phospholipase C
activation with resultant increase in
all the three factors responsible for
acne. (T- in the figure stands for
testosterone)
HISTORY

• Onset of puberty
• Neonatal acne 2 weeks of age; infantile acne 3-6 months of age; induced by maternal
adrenal hormone stimulation
• Female with severe acne; sudden in onset, hirsutism and irregular periods search for any
signs of hyperandrogenism? PCOS
• Man XXY syndrome
• Drugs induced acne steroids,phenitoin, corticotropin, lithium, isoniazid, vit B complexes,
chemotherapy
PREDILECTION

• Sebaceous areas: Face (primary site), back, upper chest and shoulder.
• On the thrunk lessions tend to be concentrated near the midline
• Type of lession inflammatory or non-inflammatory
• Non-inflammatory: commedo  closed (whitehead) or opened (blackhead), the closed one
doesnt show visible orifice
A. Closed comedo
B. Opened comedo
C. Papulopustule
D. Nodules
COMPLICATIONS

• Atrophic scars boxer scar (wide, sharply demacarted), rolling scar(shallow, wide, flat,
undulating) , iceprick scar
• Hypertrophic scars Keloids
• Transien macular erythema post acne
• Hyperpigmentation post inflammation
LABORATORIES

• Unnecessary unless hyperandrogenism acne is suspected

• Measure DHEAS serum level, total testosterone and free testosterone level
• Excess androgen can by produced by either adrenal or ovary
• Additional test: LH to FSH ratio; 17-hydroxyprogesterone to differentiate adrenal or ovovarian
source of androgen
• PCOS : serum testosterone > 150-200mg/dL or and increase of LH to FSH ratio >2
• Greater elevation of testosterone level is found in ovarian tumor
• DHEA > 4.000-8000 ng/dL may indicated congenital adrenal hyperplasia, >8000 may indicated an
adrenal tumor
• Testing should be obtained (in female) just prior to or during menstrual cycle, any contraceptive use
should be stopped 1 month prior to testing
DIFFERENTIAL DIAGNOSIS

• Comedonal acne: dd/ foliculitis, hyperplasia of sebaceous gland,

• Inflammatory acne: dd/ rosaceae, seborreoik dermatitis, acneiform eruption after steroid or
occupational acne, contact dermatitis, perioral dermatitis, acne mechanica
TARGET OF ACNE TREATMENT:

• Normalize the keratinocyte proliferation

• Decrease sebaceous gland activity
• Decrease the P acnes activity
• Exert an antiinflamatory effect
TREATMENT ALGORITHM FOR ACNE
TOPICAL TREATMENT

• Retinoid  tretinoin 0,025%, 0,05%, 0,1%; adapalene 0,1%, 0,3%, tazarotene 0,1%
• Antimicrobial
1. Benzoil Peroxide 2,5%, 5%, 10%; hydrolysis of TG; there is no resistance of BP makes it ideal for
combination therapy
2. clindamycin 1%, Erytromycin2%; dapsone
• Sulfur 5-10%  antibacterial activity by inhibition of PABA (para-amino benxoic acid which is an
essential substance for P acne growth); keratolytic properties; inhibition of the formation of free
fatty acid, alone or be combined with resorcinol 2% or sodium sulfacetamide
• Azeleic acid 20% antimicrobial and comedolytic properties, also and inhibitor of tyrosinase thus
may decrese HPI (safe in pregnancy)
• Salicylic acid (B-Hydroxy Acid) 0.5-2%decrease cohesion of keratinocytes, promote exfoliation,
RETINOID

• Bind to and activate nuclear retinoic acid receptor (RAR) interfere with gen transcript in cell
proliferation-differentiation, melanogenesis and inflammation
• SE: contact iritation, sunburn due to thinning of stratum corneum,
• Suitable for acne maintenance medicine
• Generic retinoid inactivated by benzoil peroxide (except adapalene) and photolabileused in
bedtime only
SYSTEMIC THERAPY

• ANTIBIOTICS:
• Tetracycline  decrease in free fatty acid, 500-1000 mg/day, taken on empty stomach. SE: hepatotoxicity, GI
upset, Brain Pseudotumer (if being used togather with oral retinoic); thrombocytopenia purpura,
hypersensitivity reaction, uremia, may cause irreversible yellow brown staining in teeth; should not adminstered
to pregnant woman (inhibit sceletal growth of babies) and children <9 y.o
• Doxycycline and minocyline 100-200mg/24hours. SE minocycline: blue plack pigmentation esp in acne scars,
vertigo. SE minocyline autoimmune hepatitis, SLE-like syndrome, DRESS (drug reaction eusinophilia and
systemic syndrome
• Macrolid: ertromycin resistent P.acnes> thus limiting it used for pregnant woman and young children;
azitromicyn. SE: GI upset and diarrhea
• Trimethoprim sulfametoxazole. SE: SJS, cutaneus hypersensitivity, GI upset, aplastic anemia
• Clindamicyn : rarely used? Because of the risk of pseudomembrane colitis?. Dapsone 50-100mg daily. SE:
hemolytic anemia in G6PD deficiency
HORMONAL THERAPY FOR ACNE

• Oral contraceptive 1)supressing LH production decrease androgen, 2)increase SHBG

decrease free testosterone; 3)inhibit the 5a reductase activity thus reduce conversion of
testosterone to DHT; 4) direct antiandogenic effect on sebocyte and keratinocytes. Progestin
combined with low dosage of estrogen. SE: weight gain, water retension, nausea, hypertension,
abnormal menses, breast tenderness, melasma
• Glucocorticoid anti-inflammatory effect, short term used,
• GNRH agonistused in ovarian hyperandrogenism
• ANTIANDROGEN: 1)Spironolactone Aldosteron antagonist androgen receptor blocker and 5-
a reductase inhibitor. SE: diuresis, hyperkalemia, iregullar menses, breast tenderness, headache and
fatique. 2) Cyproterone acetate progestional antiandrogen. 3) flutamide—strong antiandrogen
ORAL RETINOID

• Isotretionin  recommended for severe recalcitrant nodular acne

• Inhibition of sebaceous activity, P. acnes activity
• SE: TERATOGENIC (impair organogenesis esp in 3rd semester, because it doesnt mutagenic, no
evidence that its harm to fetus concieved by a man) ; skin and mucous membrane dryness,
cheilitis, xerophtalmia, keratitis, conjuctivitis, optic neuritis, pseudotumor cerebri, psychiatric
effects?, elevated TG, Acute hepatisis, osteopenia.
• Dose: 0.5-1mg/kg/day with typical 20 weeks course
INTRALESION CORTICOSTEROID

• 0.05-0.25 mL/lession (2.5-10mg/mL suspension of triamcinolone acetate)

• SE: atrophic and hypopigmentation
PHOTOTHERAPY FOR ACNE

• UV B low absorb through follicle,and risk for carcinogenic potensial

• Narrowband 407-420nm Blue/red light  spesificly targeting on p.acnes’s cyproporphirine III
 absorbed bacterial destruction, twice weekly 15-45 minutes sessions
• Photodinamic therapy with ALA (aminolevulinic acid) 1 hour prior to light therapy ALA
taken by philosebaceous unit converted protoporphirine IX oxygen species destruction
of sebaseous gland
ACNE VARIANS

• Neonatal acneup to 20% healthy newborns, spontaneously resolve

• Infantile acne  due to transient elevation of DHEA production of immature adrenal gland
• Acne conglobata  male>female,
• Acne fulminantfebrile ulcerative acne, febrile, leucocystosis, myial-poliatralgia, hepatosplenomegaly, anemia, corticosteroid should be started earlier before isotretionin untill the
inflammation controlled
• SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and osteotis.
• PAPA syndromesterile pyoderma gangrenosum, piogenic arthritis and acne, autoimmune autosomal dominant
• Acne excoriee de jeunes filles
• Acne mechanica obstruction of pilosebaseous unit
• Morbihan disease acne with facial edema
• PCOS (3-6% of population???)
• Congenital adrenal hyperplasia
• Steroid folliculitislession usually at the same stage of development
• Occcupational acne chloracne in fungicide,insecticide, wood preservatives, may not restricted on face
• Acne aestivalis acne induced by uv radiation
• Apert syndrome acrocephatlocyndacile