Acne and Related Disorders

June 2020

John Durkin MD, FAAD

Assistant Professor of Dermatology

jdurkin@salud.unm.edu

• No relevant conflicts of interest

Goals/objectives

• Become familiar with the pathogenesis and classifications of acne

• Know the therapeutic options for acne and when to employ them

• Know the other variants of acne like eruptions including rosacea, perioral dermatitis, and hidradenitis

ACNE

• Chronic inflammatory disease of the pilosebacoues unit

• May begin in 20s or 30s or persist in adult for many years

• Highest frequency of occuring between ages of 15 and 18 in both sexes

• Neonatal and infantile acne exist

Pathogenesis

• Undoubtedly a hereditary factor

• Primary defect is formation of keratinous plug in the lower infundibulum

• Androgenic stimulation of sebaceous glands and proliferation cutibacteriumacnes

• Evidence links free fatty acid liberation by P. acnes metabolic activity as a major factor in the genesis of acne papules and pustules

Pathogenesis

• “Sticky” cells of the stratum corneum(more sticky than normal) fail to be discharged at the follicular orifice

• Entrapped sebum gets worked on by P. acnes bacterial lipase inflammatory free fatty acids

• Leyden showed the bacterial count of C. acnes is much higher in patients with acne compared to those without 15,000:0 for ages 11 to 15 and 85,000:590 from ages 16 to 20

• Beneficial effect of tetracycline is obtained by the reduction in C. acnes and reduction in free fatty acids

Acne and androgens

• Patients with acne will often have hyperandrogenism but the exact androgenic substances vary from study to study (DHEAS, LH, Testosterone), also see decreased sex hormone binding globulin

• Important numbers:

• DHEAS >800 – Adrenal tumor

• CAH: DHEAS 400-800

• Ovarian tumor suggested by tesosterone levels above 200

• Things that worsen AV:

• Steroids, Neuroleptics, Lithium, Cyclosporin

AV – Complications

• Scarring • Dermabrasion, punch excision, laser

resurfacing

• PIH from acne lesions

• Pyogenic granuloma formation • In isotretinoin treated patients

• Osteoma cutis from long standing acne vulgaris

• Solid facial swelling: Persistent firm swelling (morbihans disease)• AV or acne rosacea

• Responds to corticosteroids or isotretinoin

AV Complications: Keloids

Acne Conglobata

• Numerous comedones, large abscesses, sinuses, cysts, grouped inflammatory nodules

• Pronounced scars after healing

• Can be associated with HS, dissecting cellulitis of the scalp, pilonidal cyst

• Men more common than women

• Tx isotretinoin

Acne fulminans

• Rare, severe form of cystic acne occurrring mostly in teenage boys

• Nodules undergo swift suppurative degeneration leaving ragged ulcerations mostly on chest and back

• Face is usually less severly involved

• Fever and leucocytosis common

• *Polyarthralgia, polymyalgia, destructive arthritis have been reported in association with it

• *Focal lytic bone lesions may be seen

• Treat with prednisone and isotretinoin

Acne Variants

• Tropical Acne:• Nodular acne on back buttocks and thighs in tropics during hot

humid summers• Face is spared, comedones are sparse

• Premenstrual acne:• Some evidence progesterone mediated, OCPs will prevent

• Preadolescent acne:• Neonatal (neonatal cephalic pustulosis): common and limited to

first 4 weeks of life, a few days after birth, has male predominance – Malasezia fur fur

• Infantile acne: acne that persists beyond neonatal or begins in infantile period

• Childhood acne: uncommon has male predominance, usually limited to face, duration is variable

• Can use Tretinoin etc even oral retiods in babies

Neonatal and Childhood Acne

Acne Variants

• Acne aestivalis • women btw. 25-40; starts in spring and resolves by fall; treat with retinoic

acid

• Acne Venenata -• Contact with a variety of acnegenic chemicals produces comedones

• Chlorinated hydrocarbons (chloracne), cutting oils, petroleum oil, coal tar

• Acne may develop in sites of radiation therapy for malignancy

• Acne cosmetica –• Persistent low grade on chin and cheeks

• Pomade acne –• Common in African Americans,

• Can recommend Mineral oil which is less comedogenic than pomade

Acneiform eruptions

• Not necessarily confined to usual sites

• Often sudden onset, monomorphous, appear in a patient well past adolescence

• If secondary to drug begins within days, has fever, resolves when drug is stopped

• May include acne venenata (chloracne)• Most potent: polyhalogenated hydrocarbons: Dioxin

• Eruptions secondary to iodides like IV contrast media or potassium iodide

Acneiform Eruptions

• Bromides, testosterone, cyclosporine, antiepileptics, lithium, EGFR inhibitors, tyrosine kinase inhibitors, and systemic corticosteroids

• Steriod Acne• Usually papular, but origin still comedonal

• increase fragility of pilosebacous unit

Which variant of Acne?

• Tropical Steroid

Acne Guidelines

2016

Grading/Treatment

Microbiologic testing

• Typically not useful

• Helpful in Gram negative folliculitis (uniform and eruptive pustules, rare nodules in perioral and perinasal area usually in the setting f prolonged tetracycline use, caused by klebsiella and serratia

Endocrinologic testing

• Indications: prepub: acne, early-onset BO, axillary or pubic hair, advanced bone age, genital maturation• Growth chart and hand film for bone age before

hormonal testing

• In post pub females: infrequent menses, hirsutism, androgenetic alopecia, infertility, polycystic ovaries, clitoromegaly, truncal obesity

• Free and total testosterone, DHEA-S, androstenedione, LH, FSH

Topical Treatments

• BPO is effective is prevention of bacterial resistance, should be used for patients on systemic or topical abx

• Erythromycin and clindamycin should not be used as monotherapy

• Azelaic acid is useful in PIH

• Topical dapsone is recommended for inflammatory acne, particularly in females

• Limited evidence for sulfur, nicotinamine, resorcinol, sodium sulfacetamide, AlCl, and Zinc

Systemic abx

• Moderate, severe acne, or acne resistant to topical treatment

• Doxy = mino > tetracycline

• Erythromycin and azithromycin should only be used in those who cannot tolerate tetracycline. Erythromycin should be restricted due to resistance

• TMP/SMX has limited data for use in acne

• Use BPO to limit resistance

Hormonal agents

• Spironolactone is useful in select females

• Oral corticosteroid therapy can be of temporary benefits in severe inflammatory acne while starting standard treatment

• In patients with adrenal hyperandrogenism, low-dose oral corticosteroids are recommended

• Estrogen-containing OCPs are effective

OCPs

• FDA approved: ethinylestradiol/norgestimate, ethinylestradiol/norethindrone acetate/ferrous fumarate, ethinylestradiol/drospirenone, and ethinylestradiol/drospirenone/levomefolate

Other therapies

• Limited evidence for PDL, glycolic acid, salicylic acid peels

• Intralesional steroids are effective in the treatment of individual acne nodules

• Additional studies are needed for PDT with or without ALA

• Limited data for tea tree oil (one study showed it was comparable to BP)

Diet in acne

• High glycemic index may be associated with acne

• Some dairy, particularly skim milk, may influence acne

AV Treatments: Topical

• BPO:

• Reduces P. acnes and may be comedolytic

• Retinoids:

• May take 8-12 weeks for improvement

• Promote normal desquamation of follicular epithelium –reduce comeodnes, inhibit dev new lesions

• Also anti-inglamatory (TLR 2 inhibition!)

• All Category C in preg, Tazarotene category X

• Topical antibacterials: clinda and erythro - *Category B

• Sulfur based topicals, resorcin and salicylic acid still useful if the newer topical medicines not tolerated

• Azeleic Acid – Category B

Acne vulgaris - Treatments

• Tetracycline:• Safest and cheapest choice• 250-500 mg QD-QID• Take ½ hour before meals• *May take 4-6 weeks before response is noted

because the action is preventative• About 5% develop candidiasis • Staining of growing teeth precludes its use in

pregnant women and in children under age 9 or 10

• Avoid tetracycline when renal function impaired

• Ca and Iron effect absorbtion, must be taken ½ before or 2 hours after meal

AV - treatments

• Minocycline:• More effective than tetracycline• *Randomized double blind showed 100 mg po qd

superior to 500 mg tetracycline• Absorption less affected by milk and food than

tetracycline• Side effects: Vertigo, hepatitis, serum sickness, Drug

induced Lupus• Staining of teeth and pigmentation in inflammed oral

tissues may develop

• Doxycycline:• More sun sensitizing (most)• More GI side effects

AV - treatments

• Erythromycin:• In pregnant women requiring oral therapy• Side effect is mostly GI upset• *250 – 500 mg two to four times daily

• Clindamycin:• No one uses systemically b/c risk of pseudomembranous colitis

• Sulfonamides:• Occasionally prescribed but avoided secondary to potential of drug

eruption

• Dapsone • may be used in severe acne conglobata but isotretinoin is preferred

• Bacterial Resistance:• Taper off of medications as much as possible• Use Oral agents in combination with BPO

Hormonal therapy

• OCPs• Estrogens suppresses the uptake of testosterone by sebaceous

glands

• Progesterones may trigger or exacerbate acne in women

• Prolonged treatment OCPs may be necessary to have an effect

• Spironolactone• Effectively reduces circulating androgens by preventing their

uptake into cells May need several months to see benefit

• Dexamethasone may also reduce androgen excess

Vitamin A

• Isotretinoin • 0.5 – 1 mg / kg / day for 15 to 20 weeks

• For greatest chance of remission pts should get 120 -150 mg / kg over the 5 month treatment period

• Multiply weight kg by 3 gives you total number 40mg capsules needed to obtain 120 mg/kg

• If severe may give 2 mg / kg / day

• 40-60% remain acne free after a single course

Isotretinoin

• Side effects:• Severe birth defects: Effects CV, Nervous

system of fetus• Increase TG, LFTs, Granulocytopenia, HA (PTC),

blurry vision, Osteopenia (can be osteolytic), Myalgias/arthralgias, Crohn’s disease, Depression, NVD, photosensitivity, hair loss

• Xerosis: may lead to SA colonization nasal mucosa• Skin abscesses, staph conjunctivitis (can be

avoided with mupirocin to the nares bid)

• Worsening of acne in first month, occasionally requires prednisone

Gram-negative folliculitis

• Patients treated with long-term antibiotics

• Pts develop superficial pustules 3 to 6 mm flaring out nares or fluctuant deep-seated nodules

• Culture reveals Klebsiella, E. coli, Enterobacter, or proteus

• This disease has declined with decreased use of long term antibiotics

• Isotretinoin is very effective treatment of choice and alone will eliminate colonization of these organisms from the nares

• Can also treat with bactrim or amoxicillin

Acne Keloidalis Nuchae

• Persistent folliculitis/perifolliculitis of back of neck

• Evolves into keloidal plaques, even sinus tracts

• Persistent free hairs in the dermis may cause the prolonged inflammation

• Treat with potent topical steroids +/-tretinoin

• ILK10 for inflammatory follicular lesions

• ILK40 for keloidal plaques

• Excision of plaques followed by topical imiquimod/ILK can be effective

Hidradenitis Suppurativa (acne inversa)

• Occurs primarily in skin folds with apocrince glands and terminal hairs (primary site of inflammation is the terminal hair)

• Buttock and submammaryinvolvement not uncommon

• Women 4:1 men

• Pts are often overweight

• Rarely SCC (after 19 years of disease), interstitial keratitis, spondyloarthropathy, and amyloidosis may complicate hidradenitis suppurativa

HS - treatment

• Chronic disease

• Topical clinda, oral tetracyclines, ILK

• Incision and drainage strongly discouraged

• *Tailor antibiotics to cultured organism sensitivities

• Isotretinoin is effective in some cases, but remission seldom follows its use

• Infliximab, etanercept, adalimumab, and Finesteridereported beneficial

• Nd:YAG laser / CO2 laser

• Wide surgical excision is most effective at limiting recurrence• Most beneficial in the axillary vaults

Dissecting cellulitis of the scalp

• Aka Perifolliculitis capitis abscedens et suffodiens

• Chronic suppurative disease with numerous follicular and perifollicular inflammatory nodules• Nodules suppurate to form intercommunicating sinuses

• Adult AAM most commonly affected

• Treatment• Intralesional steroids and isotretinoin at 0.5 to 1.5

mg/kg/day for 6 to 12 months may be successful• Length of remission after isotretinoin variable

• Oral antibiotics occasionally produce good results• If S. aureus cultured: oral rifampin and clindamycin

effective

• Laser hair removal has led to involution of disease

• Surgical excision may also be beneficial

Acne miliaris necrotica (acne varioliformis)

• Pruritic Follicular vesicopustules on the scalp

• Rupture and dry up

• S. aureus may be cultured

• Treatment: • abx (cx-sensitive) or mino / tetracycline

• Doxepin if they pick at lesions

Rosacea

• Persistent erythema with peri-ocular sparing• Erythrotelangiectatic type –

– Prominent prolonged (> 10 minutes) flushing to various stimuli (stress, hot drinks, alcohol)

– Burning, stinging sensation accompanies the flush– Over time skin may become more purple – Telangiectasias

• Papulopustular –– Red central face with erythematous papules, pinpoint pustules

• Glandular –– Predominantly men with thick sebaceous skin– Papules are edematous, pustules are large (0.5-1.0 cm), cysts may be

present– Frequent history of adolescent acne– Flushing and telangiectasia less prominent– Rhinophyma is most common in this subtype

Morbihan’s disease: edema of forehead, eyelids, and cheeks affecting papulopustular and glandular types

Which type of Rosacea does this patient have?

Rosacea

• Etiology unclear

• Pts with abnormal vasomotor response to thermal and other stimuli

• Chronic solar damage is a contributor

• Chronic vasodilatation leading to compromise of lymphatic drainage leads to telangiectasia and fibrosis

• Demodex and H. Pylori have been extensively studied and DO NOT appear to be central to the etiology

Rosacea

• Ocular findings – Can be considered fourth type• Blepharitis, recurrent chalazion, conjunctivitis

• Keratitis, iritis, episcleritis

• Abnormal Schirmer test in 40% (Dry eyes)

• c/o gritty stinging sensation in eyes

• Extra-facial -• Flushing of ears, lateral face, neck, upper chest, scalp

• Papules and pustules on the scalp or ear lobes

• Topical steroid use –• Steroid induced erythema and pustules

• Tx with tacrolimus, Abx

Rosacea - treatment

• Physical blocking sunscreens best and best tolerated useful in all types Rosacea

• Erythema:• Cosmetic coverage with light green tint• PDL laser treatment• Elidel, protopic – May pretreat with steriod x 1 week to increase tolerability

(burning)• Propranolol for symptomatic flushing• Oxymetazoline 1% cream (Rhofade, same ingredient as Afrin)• Brimonidine 0.33% gel (mirvaso)- bad rebound redness

• Papular:• Topical metro, sodium sulfacetamide, sulfur cleansers, azelaic acid (all also

help erythema)• Oral ABx

• Glandular• BPO, topical clindamycin• Oral antibiotics tetracycline or minocycline• Isotretinoin in lower dose and as long term suppressant (relapse often occurs in

a few weeks)

Pyoderma faciale

• Rare

• Superficial and deep abscesses, cystic lesions, and sometimes sinus tracts

• Lesions contain greenish or yellowing purulent material

• Mostly postadolescent women

• *Distinguished from acne by the absence of comedones, rapid onset, fulminating course, and absence of chest/back involvement

• Many consider it a severe rosacea and label it Rosacea Fulminans

• Treatment is similar to acne fulminans:• Oral steroids for several weeks followed by the addition of isotretinoin

titrated to 0.5 to 1 mg / kg with cumulative dose of 120 – 150 mg/kg• Steroids may be discontinued after two weeks of isotretinoin

Pyoderma faciale

Perioral dermatitis

• Common perioral eruption of discrete papules

• Burning sensation may be present, itch not major complaint

• Almost exclusively in women between 20 and 35

• Use of fluorinated topical steroids most frequent identified cause, can be from inhalers

• Treatment is to stop steroid, start tetracycline or minocycline, topical calcineurin inhibitors

• Also can use metronidazole, azelaicacid, adapalene, topical abx

• Periorbital dermatitis –• Variant of perioral• Topical steroids implicated in cause• Treatment same

Granulomatous facial dermatitis

• Lupus Miliaris Disseminatus Faciei• Firm yellowish-brown or red 1-3 mm monomorphous

smooth-surfaced papules present on butterfly areas but also the lateral areas, below the mandible, and periorificially

• Eyelids characteristically involved (different from rosacea)

• Caseating epithelioid cell granulomas histologically• Heal with scarring (unlike rosacea), no rosacea stigmata• Long term therapy with minocycline or clofazimine is

necessary or isotretinoin may be used• Eventual self-involution is expected

Granulomatous Perioral Dermatitis in Children

• Otherwise healthy prepubertal children (more common in skin of color)

• Numerous grouped papules in perioral or ocular distribution

• Females reported with involvement of labia majora

• Because of granulomatous histology, sarcoidosis is often considered• Unlike with sarcoid, topical steroids worsen the condition and

systemic involvement is not present

• Tx: Topical calcineurin inhibitors (creams better than ointments), metronidazole, erythromycin, sulfacetamide-sulfur combinations, and oral tetracyclines or macrolide

Thank you

• jdurkin@salud.unm.edu