Acne and Acne related disorders Disorders of sebaceous

Acne and Acne related disorders Disorders of sebaceous glands and Rosacea Omar Abdulaziz Al-Sheikh, M. D. College of Medicine King Saud University

Objectives n n n Acquiring knowledge of the etiology and pathogenesis of acne and acne related disorders. Understanding the disease spectrum and various types of clinical presentations. Knowing the differential diagnosis of acne and related disorders. Acquiring knowledge of therapeutic options and their indications. to be familiar with the etiology, clinical types and treatment of rosacea.

Definition: Is a chronic inflammatory disorder of the pilosebaceous apparatus of certain body area (Face> Torso > rarely the Buttocks), resulting in greasiness and polymorphic skin eruption.

Incidence: Acne affects all skin types, the male and female ratio is virtually the same but tends to be more severe in males. 85% affects the age group 12 – 24 years 8% affects the age group 25 – 34 years 3% affects the age group 35 – 44 years

Etiology: Genetic Aspect, (Acne runs in family) other example: the case of severe acne that is associated with XXY syndrome. 2. Occupation (Environmental, Mechanical) e. g. exposure to acnegenic mineral oil (Pomade acne), dioxin 3. Drugs Oral and topical Hydrocortison (Steroid acne), Lithium, Hydantoin, contraceptives 4. Endocrine Factors (Recalcitrant Acne, POD/s, MARSH Syndrome). 1.

Pathogenesis: ( three main steps recognized and hypothesized) 1. Follicular Hyperkeratosis (the cause not fully n n n understood) theory suggest: deficiency in Linoleic acid, the effect of 5 -a reductase enzyme on converting Androgen (Testosterone) hormone to the active acnegenic and potent (Dihydrotestosterone) DHT, the direct effect of Interleukin-1 on follicular hyperkeratosis

Fig 1 Fig 2 Fig 3 Perifollicular Hyperkeratosis histology

Seborrhoea is a common feature between patients with acne. 2. Abnormal production of abnormal sebum increasing the ratio of wax ester to cholesterol and cholesterol ester and is believed to be the response of sebaceous glands to DHEA

3. Colonization of the affected unit with bacteria Propionibacterium acne and yeast named Malassezia furfur Fig 4 Malassezia furfur Fig 5 Propionibacterium acne

n. P acne is a potent activator of complement via classical pathway Fig 6 Fig 7

Propionobacterium acne lipases act on sebaceous fatty acid (Triglycrides) to release irritant free fatty acid and low-molecular- weight peptide an extra cellular factor that penetrate the follicular wall and stimulate Polymorphs and Lymphocytes initiating inflammation Fig 8

n Hydrolytic enzymes released from the activated complement antibodies complex together with exoenzymes produced from P acne cause rupture of follicular wall Fig 9

n Once the wall is damaged Various agents (prostaglandin-like substance, amino acid, short chain fatty acids) that are produced by the inflammatory cells and P acne extrude to the dermis causing more inflammation

Clinical features: (Acne and acne related Disorders) Acne Vulgaris: Papules: (Less than 0. 5 cm) 1. n Comedones (Open “Blackheads” or closed “Whiteheads”)

Open Comedones (Blackheads) Fig 10 Fig 11 Open Comedones

Closed Comedones (Whitehead) Fig 12 Fig 13 Closed Comedones

n Inflammatory papules Fig 14 Fig 15 Inflammatory papules

n Pustules : Fig 16 Fig 17 Pustules

n Nodule (more than 0. 5 cm) Fig 18 Fig 19 Nodule

n Cystic acne: the cysts are usually large 1 - 4 cm Fig 20 Fig 21

2. The nodules and cysts could be associated with sinuses as in Acne inversa n Acne inversea (Hidradenitis suppurativa “a misleading name”) because it is considered by some to be a disorder of apocrine gland (Sweat gland) but In my opinion Acne inversa affects primarily the Pilo Seb. Unit and affect secondarily the sweat gland, hence the correct name Acne inversa rather than Hidradenitis suppurativa is preferred.

Fig 22

3. Neonatal Acne and Infantile Acne n Neonatal acne: cause unknown but some believed is due to passing of Transplacental androgen other suggest the role of Mlalassezia furfur and sympodalis. affect 1 in 5 mainly inflammatory comedones on nose and cheeks affect new born between the 1 st and 6 th week of age

Fig 23

n Infantile Acne: affect males more than females, usually between 3 and 6 months of age, and tend to be severer than the neonatal one and believed to be due to Endogenic androgen from the infant’s gonads.

Fig 24

4. Recalcitrant Acne Affect Women and associated with (Adrenal hyperplasia "11 -B- or 21 -B hydroxlase deficiencies) acne is usually nodulocystic

5. Acne Fulminans Affect youngsters 13 – 17 years of age, very severe with ulceration and puss discharge, associated symptoms include (fever, malaise, myalgia, arthritis and bone pain) laboratory investigation shows ESR Can be induced by starting the patient on high dose of isotretinion (Roaccutane).

Fig 25

6. Acne Conglobata Very severe Acne, Nodulocystic form with abscess formation, affect Torso more than the face, usually associated with XYY Syndrome.

Fig 26 Fig 27

7. Acne Agminata (Lupus Milliaris Disseminatus Faciei) Some believe it is form of Rosacea (Granulomatous type), diagnosis is made at Histological base, Caseating Granulomata at the dermal level.

Fig 28

8. Acne as part of other syndromes n n n MARSH Syndrome (Melsma, Acne, Rosacea, , Seborrhoeic eczema, and Hirsutism) Acne Conglobata Favre Racouchot syndrome elderly with elastosis as part of Helioderma, sun exposure is a predisposing factor. Polycystic ovarian syndrome Atrophoderma vermiculatum as part of so called Ulerythema ophryogenes, in Noonan Syndrome, de Lange Syndrome, and Rubinstein-Taybi Syndrome Not considered acne

9. Occupational I Environmental Chloracne rare forms of acne affect patients exposed to Halogenated Hydrocarbons or who ingested Chlorinated Phenols (Dioxin) n Pomade acne or known as Oil Folliculitis n n Acne Aestivalis or so called Mallorca Acne

Occupational II mechanical acne Folicullitis Nuchae or so called Acne Keloidalis n Pseudofollicultis barbae n n Acne excoriee as part of Psychodermatosis

TREATMENT Note: All medications used for the treatment of acne act as: 1. Anti comedonal 2. Anti inflammatory 3. Anti microbial

Topical Keratolytic n n n Retinoid ( Retinoic acid 0. 025, 0. 05, 0. 1%) Adapalene (Differin 0. 1%) Salicylic acid Benzoyl peroxide (peeling agent and antimicrobial) Azelaic Acid (10, 15, 20 %)

Topical Antibiotic Topical clindamycin (Dalacin T) n Erythromycin n Mupirocin (Bactroban) n Sodium Fusidic acid (less significant in the treatment) n

Systemic therapy n 1. 2. 3. 4. Antibiotic (Macrolides and Tetracylines) Tetracycline Doxycycline Minocycline (blue grey discoloration and drug induced LE) Azithromycin

n Systemic Retinoids : § Isotretinoin caps (Roaccutane): 0. 5 – 1 mg/kg The most effective drug for acne. Indicated for severe forms (nodulocystic and fulminant) but also for milder forms associated with scarring or with significant psychological impact. Relapse is minimal with cumulative dose of 120 – 150 mg/kg. Side effects include: cheilitis, dryness, alopecia (less frequent than with acitretin), photosensitivity, xerophthalmia, decreased night vision, keratitis, benign intracranial hypertension (incresed risk with concomitant use of tetracyclines), photosensitivity, hypertriglyceridemia, hypercholesterolemia, elevated liver enzymes, depression (controversial), skeletal hyperostosis, myalgias. Teratogenicity : Retinoid - induced embryopathy. Pregnancy category X. Pregnancy must be prevented during treatment and for at least 1 month after discontinuing the drug. § § §

Other forms of therapy Systemic steroid (Prednisolone): for acne fulminans and intralesional steriods for cystic acne. n Photodynamic therapy i. e. Laser therapy and phototherapy (Less significant) n SMT D 002 is a new promising and potentially safe medication (Oxybutynin chloride), it has successfully completed two Phase I trials in healthy volunteers and believed to treat seborrhoea, a symptom of Parkinson's disease and the primary cause of acne. Topical formulation of the drug is currently being developed by Summit company. n Hormonal therapy (Anti-androgen) Spironolacton (Potassium sparing agent) and Metformin as (Hypogylcemic agent) in treatment of PCOS (Polycystic Ovary Syndrome) have good results on acne n

Rosacea - A controversial topic in dermatology largely because of its uncertain pathophysiology and clinical variation. Erythema of the central face that has persisted for months or more. Primary features: flushing, papules pustules and telangiectases. Secondary features: burning, stinging, edema, plaques, dry appearance, phyma, peripheral flushing and ocular manifestations.

Epidemiology Common in caucasian population n Fair skinned individuals n women>men n Onset typically begins after age 30 n

Etiology and pathogenesis n 1) Vascular reactivity: n Rosacea is induced by chronic repeated triggers of flushing exposure, they include: n 1) Hot or cold temperature 7) Sunlight 2) Hot drinks 3) Spicy foods 4) Alcohol 8) Emotional disteress 5) Certain cosmetics 9) Topical irritants 6) Medications n n n

Etiology and pathogenesis n 2) Dermal matrix degeneration and endothelial damage Inherent problems with vessels permeability n Delayed clearance of inflammatory mediators and waste products n Photodamaged connective tissue (solar elastosis is a common background on which rosacea histologic features are superimposed n

Etiology and pathogenesis n The role of microbe – induced follicle based inflammation Commensal organisms which reside in hair follicles and sebaceous glands may trigger folliculocentric inflammatory papules. n Demodex folliculorum (mite) or associated bacteria (bacillus oleronius). n

Sub-type classification Sub types were defined by the National Rosacea Society (NRS) expert committee in 2002. 1) Erythematotelangiectatic : persistent erythema and telangiectasias on the central face. 2) Papulopustular: papules and pustules predominate on convex areas on a background of persistent erythema 3) Phymatous: patulous follicular orifices, thickened skin and nodularity Most often affect the nose (rhinophyma) Almost exclusively in men 4) Ocular: Blepharitis is the most common feature (mebomian gland dysfunction) Conjuctivitis, iritis, scleritis, keratitis

Erythematotelangiectatic Rosacea Fig 29

Papulopustular Rosacea Fig 30

Rhinophyma Fig 31

Rosacea variants Granulomatous rosacea: Rosacea variant characterised by monomorphic yellow brown or red papules/ nodules located on the cheeks and periorificial skin. Granulomas on histology The background facial skin is otherwise normal

Differential Diagnosis Full and detailed history (including medications)is required, Medications that induce flushing include : all vasodilators, calcium channel blockers, nicotinic acid, morphine, amyl and butyl nitrite, cholinergic drugs, bromocriptine, tamoxifen, cyproterone acetate, systemic steroids and cyclosporine. Diagnosis is made clinically Differential diagnosis include: Seborrheic dermatitis Steroid folliculitis/Perioral Dermatitis Acne vulgaris Erythromelanosis faciei and keratosis pilaris rubra Lupus erythematosus Lupus miliaris disseminatus faciei

Treatment Sunscreens n Avoidance of aggravating factors. n Topical medications include: n n n n Metronidazole Sodium sulfacetamide and sulfur Azelaic acid Benzoyl peroxide Tretinoin Erythromycin and Clindamycin

n n n Oral medications include: Tetracyclines are the most commonly prescribed oral medications for the treatment of rosacea. They act by their anti-inflammatory effects Erythromycin (for children with granulomatous perioral dermatitis) Isotretinoin

Laser and light therapy Laser and Intense Pulsed light IPL is useful in treating persistent erythema and telangiectasias Pulsed dye laser (585 or 595 nm) Potassium-titanyl phosphate laser KTP 532 nm, for superficial small telangiectasias. • Deep facial vessels require longer wavelengths : Diode laser (810) • The long pulsed alexandrite laser (755 nm) • Long pulse ND: YAG (1064 nm)

Treatment of Phymatous Rosacea § § § Early to moderate Phymatous changes could be treated with Isotretinoin. Advanced phyma is treated with surgery or surgery followed by isotretinoin. Scalpel tangential excision Electrosurgery Laser CO 2 ablation.

Fig 1, 2 www. scf-online. com/. . . /keratinization 38_e. htm keratinization of the duct of the hair follicle. www. nlm. nih. gov/. . . /ency/imagepages/2087. htm open (Blackheads) comedones, Medical Encyclopedia Fig. 3 Fig 4. Malassezia furfur www. doctorfungus. org/thefungi/Malassezia. htm Closed comedones Skin and. allergy centre Fig 5 Fig 6 www. ohiohealth. com/bodymayo. cfm? id=6&action=t. . . Mayo Foundation for Medical and research. Fig 7 Fig 8 bacterial colonization www. healthcaresouth. com/pages/acnewhatis. htm Fig 9 Breakage of follicular wall www. healthyskinbydesign. com/acne. cfm papule Fig 10 open comedones www. healthcaresouth. com/pages/acnewhatis. htm Fig 11 Fig 12 closed comedones www. healthcaresouth. com/pages/acnewhatis. htmfig www. dermalogix. net/acne. html open and closed comedones schematic pictures www. dermalogix. net/acne. html proriobionacterium acne in pilosabaceous unit www. healthyskinbydesign. com/acne. cfm. follicular hyperkeratosis in acne Fig 13 Fig 14 Fig 15 Fig 16 www. healthyskinbydesign. com/acne. cfm pustule Fig 17. Courtesy of Skin and allergy centre Fig 18 www. healthyskinbydesign. com/acne. cfm nodule Fig 19 nodule www. acnekil. com/What's_Acne/photo_gallery 2. htm Fig 20 Fig 21 Courtesy of Skin and allergy centre Fig 22 Courtesy of Skin and allergy centre Fig 23 www. adhb. govt. nz/. . . /Benign. Lesions. htm at neonatal dermatology benign lesions Auckland district health board. Fig 24 Courtesy of Polonia, second edition Fig 25 Fig 26 Courtesy of Skin and allergy centre Fig 27 Acne conglobata www. consultantlive. com/show. Article. jhtml? arti. . . Fig 28 acne Agminata Granulomatous rosacea in infants. Report of three cases and discussion of the differential diagnosis João Borges da Costa, Sousa Coutinho V, L Soares de Almeida, M Marques Gomes Ph. DDermatology Online Journal 14 (2): 22

n n n Fig 29, courtesy of Rook 2010 Fig 30, courtesy of Fitzpatrick 2008 Fig 31, courtesy of Polonia 2008

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