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Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

Acne vulgaris affects over 80% of the population at some point in their lives with physical manifestations that can cause intense distress as well as psychological problems, such as anxiety, depression, social withdrawal, and even suicidal ideation.[1,2] Thus, proper diagnosis and differentiation of the various forms of acne and targeted therapeutic choices are important for clinicians.

Image courtesy of Wikimedia Commons/OpenStax College.

Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

Acne begins with the formation of the microcomedo at the infundibulum of the hair follicle, located in the pilosebaceous unit. Increased proliferation and cohesiveness of the dead corneocytes lead to buildup and massive expansion within the follicle. Androgens also promote sebaceous gland hypertrophy and increased sebum production. Through continuing expansion, the loosely packed dead cells and sebum become densely compacted, forming whorled lamellar concretions. The opening to the surface of the skin is narrow; immense force builds up within the comedo, causing wall rupture and resultant inflammation from the leaked sebum and keratinocytes (shown). P acnes, an anaerobic, gram-positive rod-shaped bacteria that is native to normal skin flora, thrives in the sebum-rich comedones and further promotes inflammation and wall rupture. P acnes is thought to influence the innate immune system through interactions with toll-like receptor-2 (TLR2)[3] and possibly T helper cells 1 and 17 (Th1 and Th17, respectively) to produce interleukin 17 (IL-17) cytokines.[4] Papules, pustules, nodules, and cysts result from this inflammatory process.

Image courtesy of Medscape.

Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

Noninflammatory acne includes open and closed comedones. Open comedones, or blackheads, are dilated follicular openings filled with keratin (shown). Melanin deposition and lipid oxidation may be responsible for the black color.

Image courtesy of Medscape.

Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

Closed comedones, or whiteheads, however, present as small skin-colored, nonerythematous papules that do not have an associated follicular opening (shown). Their subtle appearance can be better appreciated through palpation or with the use of side lighting.

First-line therapy for open and closed comedones is a topical retinoid; alternative therapies may include azelaic acid, salicylic acid, and comedo extraction. Side effects of topical retinoids include dryness, flaking, and erythema, which decrease with continued usage. Sunscreen is advised for all individuals who use topical retinoids due to skin irritation and the increased possibility of sunburn.[1]

Image courtesy of Wikipedia.

Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

Inflammatory acne develops from ruptured comedones and proliferating P acnes, resulting in papules, pustules, nodules, and cysts. Papules are generally 1-5 mm in diameter. The image shows numerous scattered erythematous papules with some closed comedones on the forehead of an adolescent male. These mild inflammatory lesions require the introduction of a topical antimicrobial agent, such as benzoyl peroxide, clindamycin, or erythromycin in addition to topical retinoid therapy. Several studies provide evidence for increased efficacy, decreased inflammation, and decreased antibiotic resistance when benzoyl peroxide or a topical retinoid is combined with an antibiotic therapy.[5-7]

Image courtesy of Medscape.

Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

Pustular acne appears as yellow, suppurative fluid-filled papules (shown). Neutrophilic inflammation predominates in the formation of these lesions.[1] Antimicrobials are used to treat these inflammatory lesions. Patients with pustules should consider oral antibiotic therapy with tetracyclines or, less commonly, macrolides on the basis of the severity, distribution, and response of the pustules to topical antimicrobial agents.

Image courtesy of Medscape.

Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

As a result of continued inflammation after the comedonal, papular, and pustular stage; nodules can form deep in the dermis (shown). These lesions have a firmer texture than pustules and are painful to the touch.

Image courtesy of Wikimedia Commons/James Heilman, MD.

Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

The image shows a patient with severe cystic acne. Cysts are pus-filled lesions that have a fluctuant feel on physical examination and remain painful to palpation.[8] Technically, these cysts are pseudocysts because they do not possess a true epithelial lining. An injection of intralesional triamcinolone can be tried in a single cystic lesion.

Image courtesy of Medscape.

Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

The image shows a patient inflamed with multiple open and closed comedones, papulopustules, and cysts.

Nodulocystic acne consists of deep inflammatory cysts and nodules in addition to comedones, papules, and pustules. At this stage, oral isotretinoin is considered first-line therapy; it is typically administered at 0.5-1 mg/kg/day for 4-6 months (for a cumulative dose of 120-150 mg/kg).[1] For optimal absorption, isotretinoin should be taken with fatty meals. The most common dose-dependent side effects of isotretinoin include cheilitis, xerophthalmia, epistaxis (secondary to dry nasal mucosa), and eczema. The most adverse side effect is fetal teratogenicity. In 2012, the US Food and Drug Administration (FDA) approved CIP-isotretinoin for severe recalcitrant acne with the proposed benefit of more consistent absorption during fasting states compared to isotretinoin.

Image courtesy of Medscape/Emanuel G. Kuflik, MD.

Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

The image shows a patient whose back has numerous healing, crusted ulcers and erosions, as well as atrophic scarring from acne conglobata. Acne conglobata is a severe form of nodulocystic acne that can arise from preexisting acne vulgaris or as an acute-onset eruption and does not have associated systemic symptoms. It tends to affect young males and may be part of the follicular occlusion tetrad with dissecting cellulitis of the scalp, hidradenitis suppurativa, and pilonidal cysts. Acne conglobata is usually located on the chest, back, and buttocks, and generally includes papules, pustules, double comedones, extensive cysts, and nodules with sinus tracts that eventually form communicating abscesses with purulent drainage. Treatment includes systemic antibiotics, intralesional steroids, systemic glucocorticoids, and surgical intervention.[9] Oral isotretinoin can be beneficial, but it is important to begin with a low dose (maximum, 0.5 mg/kg/day). Systemic steroids before and/or during therapy may prevent acute flares. Biologic tumor necrosis factor (TNF)-alpha inhibitors have been effective in a few reports of refractory cases.[10,11]

Image courtesy of Geller AS, Alagia RF. An Bras Dermatol. 2013;88(6 suppl 1):193-6. [Open access.] PMID: 24346917, PMCID: PMC3875980.

Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

Acne fulminans (acne maligna) (shown), considered the most severe form of acne, is a rare condition that mainly affects white male teens (age, 13-16 years). The sudden onset of ulcerative, suppurative acne with systemic symptoms such as fever, polyarthritis, myalgias, hepatosplenomegaly, or malaise is usually preceded by about 1 year of mild to moderate acne vulgaris.[12] Laboratory findings include leukocytosis and elevated erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Bone involvement, especially of the clavicles or sternum, may be present; imaging studies or biopsy may differentiate osteolytic lesions from infection and malignancy. Radiographs and technetium scintigraphy detect osteolytic lesions in 50% and 70% of cases, respectively.[12] Treatment includes oral steroids (0.5-1 mg/kg/day) with slow taper; after 4-6 weeks, add oral isotretinoin (gradual titration to 1 mg/kg/day). Therapy usually lasts 3-5 months. The first few weeks of isotretinoin use can precipitate acne fulminans; use a low dose (0.25 /mg/kg/day) to treat acne in general. Acne fulminans may signify SAPHO syndrome of synovitis, acne, pustulosis, hyperostosis, and osteitis.

Source of image information: Bolognia JL, Jorizzo JL, Schaffer JV.[1]

Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

The image summarizes several causes of drug-related acne. EGFR = epidermal growth factor receptor inhibitors. Drug-related acne, or acneiform eruptions, presents in more unusual locations and at atypical ages than is seen in other types of acne, and can be resistant to conventional acne therapies.[13] The key to diagnosis is the patient's recent medication history and the clinical appearance of monomorphic papules and pustules without the presence of comedones. If possible, discontinue the suspected offending medication or switch to another agent to confirm the drug association and to potentially resolve the lesions. However, given the relatively benign nature of the lesions, it is rarely necessary to disrupt a medication regimen because of drug-induced acne.[1]

Images courtesy of Lawrence Charles Parish, MD, MD(Hon).

Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

Steroid-induced acne (shown) is an acneiform drug eruption often caused by systemic oral and intravenous corticosteroids. Topical and inhaled corticosteroids can also trigger this condition; in addition, they can be responsible for perioral dermatitis.[13] Steroids induce sebaceous gland hypertrophy, increase sebum production, and accelerate the growth of P acnes.[14] Characteristic lesions are monomorphic papules or papulopustules on the trunk and upper aspects of the arms. The presence of monomorphic lesions without comedones in conjunction with a history of steroid use is sufficient for the diagnosis. Withdrawal of the corticosteroid, when possible, is usually enough to resolve the lesions. However, steroid dependency can lead to severe, prolonged flares after discontinuation.[1]

Image courtesy of Wikimedia Commons.

Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

Acne can be a sign of anabolic androgenic steroid (shown) abuse, particularly in young males who participate in rigorous bodybuilding ("bodybuilding acne") or intensive sports ("doping acne"). These agents are structurally similar to endogenous androgens; thus, they also stimulate sebaceous glands to form acne. Approximately 50% of those who abuse anabolic androgenic steroids are affected with some form of acne,[13] which can range from papulopustules to acne conglobata to acne fulminans.[13,14] Moreover, anabolic androgenic steroid abusers often concurrently overdose themselves on vitamins; vitamins B6 and B12 can cause acne eruptions.[1,13] Other signs of abuse of these agents include gynecomastia, decreased testicular volume, striae, edema, and increased body mass index. Treatment includes immediately discontinuing the anabolic androgenic steroids and administering a standard acne therapeutic regimen.[13]

Image courtesy of Wikipedia.

Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

EGFR inhibitors (eg, cetuximab, panitumumab) are used to treat malignancies such as non-small cell lung, pancreatic, colorectal, head and neck cancers (shown). The most common dermatologic side effect of these agents is an eruption of monomorphic papules and pustules on the face, scalp, and upper trunk that appears 8-10 days after EGFR initiation and peaks in severity in the second week.[15,16] With drug cessation, the lesions resolve without scarring in 4-8 weeks,[16] but halting effective chemotherapy is not a viable option for oncology patients. A point of debate is whether pretreatment with topical vitamin K1[15,17,18] or oral tetracyclines[1] may help prevent eruptions. There are anecdotal reports of success using a standard acne regimen of antibiotics and retinoids.[1,16] Physicians should consider the potential risk of superinfection with Staphylococcus aureus, including methicillin-resistant strains, and Pseudomonas species; topical or systemic antibacterial agents are effective treatment.[1,16] TGF = transforming growth factor.

Image courtesy of Wikimedia Commons.

Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

Neonatal acne, also referred to as neonatal cephalic pustulosis, affects up to 20% of newborns from age 2 weeks to 3 months. There is a male preponderance.[19] Small papules and pustules without comedones typically appear on the cheeks and nose (shown). Possible etiologies include stimulation of the sebaceous glands from neonatal or maternal androgens or an inflammatory response to Malassezia species.[20] Neonatal acne is self-limiting, so caregivers should be reassured of the benign prognosis. Topical imidazole agents (eg, ketoconazole cream) may be helpful.[1]

Image courtesy of Chebotarev VV, Tamrazova OB, Chebotarev NV, Odinets AV. Chapter 13. Pathology: sebaceous glands, hair and nails. Dyschromia. [Russian.] Accessed April 13, 2017.

Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

Infantile acne occurs at age 3-12 months, mainly in males. Lesions usually appear on both cheeks with comedones (shown) and are more pleomorphic than those of neonatal acne (eg, papules, pustules, severe nodules, cysts). There can also be an increased incidence and severity of acne vulgaris during adolescence and a scarring risk.[21] Therapy includes topical retinoids, benzoyl peroxide, and antibiotics (erythromycin preferred). If the acne is severe or widespread enough to require oral antibiotics, the treatment of choice is erythromycin 125-250 mg PO twice daily.[22] Tetracyclines are contraindicated due to potential teeth staining and bone toxicity. Topical or intralesional triamcinolone acetonide may be used for deep nodules and cysts.[20] Some success has been reported with oral isotretinoin, but side effects include xerosis, cheilosis, and elevated liver enzymes and lipid levels.[23]

Image courtesy of Lawrence Charles Parish, MD, MD(Hon).

Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

Acne can persist into adulthood or first present in adults (shown). Postadolescent acne primarily affects women older than 25 years. The lesions tend to flare most frequently in the week before menstruation,[1,24] often present as painful papulonodules along the jawline and neck, and are frequently resistant to multiple courses of oral antibiotic therapy.[1] Treatment is aimed at controlling androgen levels, either with spironolactone (50-100 mg twice daily), which blocks androgen receptors and inhibits 5-alpha-reductase,[1] or with specific oral contraceptive pills (OCPs) (FDA-approved OCPs for acne: triphasic norgestimate-ethinyl estradiol, 35 mcg; ethinyl estradiol, graduated dose of 20-35 mcg, with norethindrone acetate; ethinyl estradiol, 20 mcg, with drospirenone, 3 mg). Combined spironolactone/OCP therapy can be used, particularly if spironolactone is being considered for treatment of acne in a female of child-bearing age. OCP use is a pivotal concern, as spironolactone can feminize a male fetus.

Image courtesy of ST Esthetic. Treatment of rosacea with a solid persistent edema. [Russian.] October 9, 2014. Accessed November 18, 2014.

Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

Solid facial edema (lymphedematous rosacea, Morbihan disease) is a rare complication of acne vulgaris that presents as a symmetrically disfiguring and nonpitting edema with persistent midface erythema (shown). It tends to appear in males in their late teens or early 20s who have a long history of acne. The underlying cause may be chronic inflammation that results in impaired lymphatic drainage and mast cell-induced fibrosis.[1] This condition persists indefinitely if left untreated, and may lead to visual impairment if left uncontrolled.[25] Limited success (incomplete/relapsing response) has been reported with anti-inflammatory drugs (eg, systemic corticosteroids, oral antibiotics, thalidomide, antihistamines) used either alone or in a combination.[26,27] Isotretinoin monotherapy (40-80 mg/day) for up to 24 months[27] or isotretinoin combined with ketotifen or clofazimine has shown promise.[25] In drug-resistant cases, clinicians can use more symptomatic treatments (eg, debulking therapy and blepharoplasty for eyelid swelling).[26]

Image courtesy of DermNet NZ.

Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

Acne excoriée (sometimes known as acne excoriée des jeunes filles or "excoriated acne of young girls") presents as comedones and inflammatory papules that patients have habitually picked and scratched (shown). As expected from the name of this condition, the lesions commonly occur in young women and, often, in patients with a history of obsessive-compulsive disorder, depression, or anxiety. Patients usually admit to being unable to resist the urge to pick at the lesions. Occasionally, the patients are dissociated and do not realize or recall the skin-picking.[29] Some patients with acne excoriée require psychiatric interventions (eg, psychotherapy) or medical therapy (eg, selective serotonin reuptake inhibitors [SSRIs]).[19] In appropriate patients, mood stabilizers, such as lithium, have been helpful in treating the skin-picking behavior, but such therapy is not ideal because acne is a known side effect of these agents.[27]

Image courtesy of Medscape.

Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

The image shows the right cheek of a female patient with several resolving papules and pustules as well as hyperpigmented macules from older lesions. Postinflammatory hyperpigmentation or erythema can result when inflammatory acne heals. Although the dyspigmentation usually fades over months, it can become permanent. This condition presents more frequently in dark-skinned individuals, specifically those with Fitzpatrick skin type IV-VI,[30] and can occur even without excoriation or manipulation of acne lesions. The recommended treatment of postinflammatory hyperpigmentation is 4% hydroquinone, a tyrosinase inhibitor, which is stronger than over-the-counter formulations and can be safely used in those older than 13 years.[31] When hydroquinone is utilized in combination with a daily topical retinoid and a mid-potency corticosteroid, its efficacy can be increased.[31] Spot treatment is preferred for patients who have a few discrete lesions, but they should be warned of the potential for the occurrence of a halo of hypopigmentation around each lesion. Field therapy should be used if hyperpigmentation is more diffuse and widespread.

Image courtesy of Ramesh M, Gopal M, Kumar S, Talwar A. J Cutan Aesthet Surg. 2010;3(2):97-101. [Open access.] PMID: 21031069, PMCID: PMC2956966.

Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

Severe inflammation from acne can result in permanent scars of three types—ice pick, boxcar (shown), and rolling—but most people have mixed scarring. Adequate acne treatment is key to preventing progression to scarring. Ice-pick scars are narrow, deep scars with sharp edges that extend deep into the dermis or subcutaneous tissue, and a depth that is greater than conventional resurfacing can reach. Thus, these scars usually undergo punch excision or grafting.[1, 32]Rolling scars have a rolling, shallow appearance from abnormal fibrous anchoring of the dermis to the subcutaneous tissue. Boxcar scars are round to oval with sharp vertical edges, and they can be shallow or deep (shown).[33, 34] Because boxcar and rolling scars are more broad on the skin surface, they require dermal filling, resurfacing, or surgical subcision (subcutaneous incision).[32] Acne scars can be classified into atrophic, as discussed above, and hypertrophic or keloidal. Often, large hypertrophic scars and sinus tracts benefit from full-thickness excision; surgeons have a choice in placement and closing technique for the best cosmetic results.[1]

Image courtesy of Wikipedia.

Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

Chloracne develops after several weeks of exposure to chlorinated aromatic hydrocarbons, typically in the axillae and groin, as well as the malar, retroauricular, and mandibular areas of the face, but the nose is usually spared.[34] Lesions appear as small cystic papules and nodules. Recurrent outbreaks can occur even years after exposure, and atrophic or hypertrophic scarring can result (shown).[35] Offending agents known to cause chloracne are found in pesticides, wood preservatives, and electrical conductors. They include polychlorinated naphthalenes, biphenyls, dibenzofurans and dibenzodioxins; polybrominated naphthalenes and biphenyls; and tetrachloroazobenzene and tetrachloroazoxybenzene.[1] Patients who are at risk of exposure to these chemicals should wear appropriate protective equipment to prevent lesions. Treatment includes removal of patients from exposure to the chemical agents as well as administration of topical/oral retinoids and oral antibiotics.

Image courtesy of Alamy.

Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

Acne mechanica results from friction or repeated mechanical obstruction, which plugs up sebaceous glands to form comedones. Culprits include chin straps, collars, suspenders, helmets, and crutches. "Fiddler's neck" or "violin hickey" has been characterized as the classic example of acne mechanica, which results from the violin constantly rubbing against the violinist's neck. The clinical diagnosis for acne mechanica is typically made on the basis of the presence of geometrically distributed areas of involvement, often very different from the common locations of acne vulgaris. Treatment is aimed at reducing or modifying contact with the inciting agent.[1]

Source of image information: Bolognia JL, Jorizzo JL, Schaffer JV.[1]

Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

To determine the most appropriate acne treatment regimen, a relevant history and thorough physical examination must be performed. In female patients, clinicians can investigate hormonal influences by obtaining detailed information about acne flares in relation to menstrual cycles and noting the use of any oral contraceptive agents. During the physical evaluation, focus on the morphology of the acne lesions as well as their distribution and severity. Signs of virilization in a female (eg, clitoromegaly, hirsutism, deepening voice) may indicate an androgenic etiology. The image summarizes the most important and pertinent elements to obtain when gathering a patient's history and performing a physical examination. Hx = history.

Source of image information: Bolognia JL, Jorizzo JL, Schaffer JV.[1]

Acne: More Than Skin Deep

Jenny Yeh, BA; Vineet Mishra, MD | April 20, 2017 | Contributor Information

This image summarizes treatment options for acne vulgaris. Topical retinoids include tretinoin, adapalene, and tazarotene. These agents normalize follicular keratinization and keratinocyte cohesion to treat existing comedones and prevent new ones.[1] Azelaic acid also alters follicular keratinization, and inhibits P acnes proliferation, which makes this agent especially effective against inflammatory lesions.[1] Salicylic acid is both comedolytic and anti-inflammatory, but it can be very irritating to the skin. Topical antimicrobials include benzoyl peroxide and antibiotics such as clindamycin and erythromycin. In general, comedo extraction should be performed on noninflammatory lesions to prevent scarring. For intralesional corticosteroids, the general recommendation is triamcinolone 2-5 mg/mL.[1]

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Poisoning Clues on the Skin: 10 Cases

Poisonings often manifest on the skin. Can you correctly diagnose these 10 patients based on their dermatologic presentations?Slideshows, April 2017
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