Acne Vulgaris (Clinical)

Overview

Epidemiology^[1,7,10,11]

• The most common skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions disease in the United States
• Affects approximately 80% of people at some point in life:
  • Frequently occurs in preadolescence, but can develop in adulthood
  • Often resolves by the 4th decade, but can persist in some patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • 20% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship will develop severe acne and scarring Scarring Inflammation.
• Demographics:
  • Boys are more commonly affected in adolescence.
  • Women are more likely to be affected as adults.
  • People of Asian and African descent more frequently suffer from severe acne.
  • Caucasians more often have mild acne.

Etiology^{[1,2,7,10,11]}

• Genetic predisposition (heritability: 50%–90%)
• Cutibacterium acnes Cutibacterium acnes A bacteria isolated from normal skin, intestinal contents, wounds, blood, pus, and soft tissue abscesses. It is a common contaminant of clinical specimens, presumably from the skin of patients or attendants. Acne Vulgaris (formerly known as Propionibacterium acnes Propionibacterium acnes A bacteria isolated from normal skin, intestinal contents, wounds, blood, pus, and soft tissue abscesses. It is a common contaminant of clinical specimens, presumably from the skin of patients or attendants. Acne Vulgaris)^[2]
  • Anaerobic gram-positive Gram-Positive Penicillins rod that is part of the normal skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions flora
  • Metabolizes sebaceous triglycerides Triglycerides Fatty Acids and Lipids → releases free fatty acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance
  • Can activate complement and stimulate an inflammatory response 
• Aggravating factors:
  • Hormonal variation:
    • During puberty Puberty Puberty is a complex series of physical, psychosocial, and cognitive transitions usually experienced by adolescents (11-19 years of age). Puberty is marked by a growth in stature and the development of secondary sexual characteristics, achievement of fertility, and changes in most body systems. Puberty or menstrual cycle Menstrual cycle The menstrual cycle is the cyclic pattern of hormonal and tissular activity that prepares a suitable uterine environment for the fertilization and implantation of an ovum. The menstrual cycle involves both an endometrial and ovarian cycle that are dependent on one another for proper functioning. There are 2 phases of the ovarian cycle and 3 phases of the endometrial cycle. Menstrual Cycle
    • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
    • Congenital Congenital Chorioretinitis adrenal hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation
    • Polycystic ovarian syndrome Polycystic ovarian syndrome Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of reproductive-age women, affecting nearly 5%-10% of women in the age group. It is characterized by hyperandrogenism, chronic anovulation leading to oligomenorrhea (or amenorrhea), and metabolic dysfunction. Polycystic Ovarian Syndrome
  • Mechanical occlusion:
    • Underwire bras
    • Headbands
    • Shoulder pads
  • Cosmetics
  • Stress
  • Medications:
    • Lithium Lithium An element in the alkali metals family. It has the atomic symbol li, atomic number 3, and atomic weight [6. 938; 6. 997]. Salts of lithium are used in treating bipolar disorder. Ebstein’s Anomaly
    • Steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors
    • Anticonvulsants
  • Diet:
    • Dairy (due to hormonal components in milk)
    • High glycemic index foods

Pathophysiology^{[1-3,7,10,11]}

Acne vulgaris Acne vulgaris Acne vulgaris, also known as acne, is a common disorder of the pilosebaceous units in adolescents and young adults. The condition occurs due to follicular hyperkeratinization, excess sebum production, follicular colonization by Cutibacterium acnes, and inflammation. Acne Vulgaris is a disorder of the pilosebaceous unit (which includes the hair follicle Hair follicle A tube-like invagination of the epidermis from which the hair shaft develops and into which sebaceous glands open. The hair follicle is lined by a cellular inner and outer root sheath of epidermal origin and is invested with a fibrous sheath derived from the dermis. Follicles of very long hairs extend into the subcutaneous layer of tissue under the skin. Cowden Syndrome and sebaceous gland Sebaceous Gland Small, sacculated organs found within the dermis. Each gland has a single duct that emerges from a cluster of oval alveoli. Each alveolus consists of a transparent basement membrane enclosing epithelial cells. The ducts from most sebaceous glands open into a hair follicle, but some open on the general surface of the skin. Sebaceous glands secrete sebum. Hordeolum (Stye)) and is characterized by 4 pathogenic factors:

• Follicular hyperkeratinization Follicular Hyperkeratinization Acne Vulgaris: corneocyte cohesiveness → hyperkeratotic plugging in the upper follicle, causing retention of sebum Sebum The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. Infectious Folliculitis and leading to a microcomedo
• Excessive sebum production Excessive Sebum Production Acne Vulgaris:
  • Androgens Androgens Androgens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth. Androgens and Antiandrogens ↑ sebum Sebum The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. Infectious Folliculitis production
  • Sebum Sebum The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. Infectious Folliculitis accumulates with keratin Keratin A class of fibrous proteins or scleroproteins that represents the principal constituent of epidermis; hair; nails; horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of type I keratin and a type II keratin, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. Alpha-keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to gene duplication. Seborrheic Keratosis → comedo formation
• Colonization Colonization Bacteriology of follicles by C. acnes:
  • Sebum Sebum The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. Infectious Folliculitis acts as a nutrient and growth medium for C. acnes.
  • C. acnes produce enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes that degrade keratin Keratin A class of fibrous proteins or scleroproteins that represents the principal constituent of epidermis; hair; nails; horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms a coiled-coil alpha helical structure consisting of type I keratin and a type II keratin, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. Alpha-keratins have been classified into at least 20 subtypes. In addition multiple isoforms of subtypes have been found which may be due to gene duplication. Seborrheic Keratosis and stimulate inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation.
• Inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation:
  • C. acnes trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation an innate immune response Innate Immune Response Immunity to pathogens is divided into innate and adaptive immune responses. The innate immune response is the 1st line of defense against a variety of pathogens, including bacteria, fungi, viruses, and parasites. In essentially the same form, the innate type of immunity is present in all multicellular organisms. Innate Immunity: Barriers, Complement, and Cytokines → proinflammatory cytokine release → activation of neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation → mild perifollicular inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation → inflammatory papule Papule Elevated lesion < 1 cm in diameter Generalized and Localized Rashes or pustule Pustule Blister filled with pus Generalized and Localized Rashes development
  • Neutrophils Neutrophils Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. Innate Immunity: Phagocytes and Antigen Presentation and C. acnes release enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes → follicular rupture into the dermis Dermis A layer of vascularized connective tissue underneath the epidermis. The surface of the dermis contains innervated papillae. Embedded in or beneath the dermis are sweat glands; hair follicles; and sebaceous glands. Skin: Structure and Functions → a more marked and deeper inflammatory response → inflammatory nodule Nodule Chalazion (also called a cyst) development

Clinical Presentation

Classification and presentation of acne lesions^[5,7,9-11]

Acne may be noninflammatory, inflammatory, or a mixture of the two.^[5]

Noninflammatory acne Noninflammatory Acne Acne Vulgaris ( comedones Comedones Acne Vulgaris):

Hyperkeratotic plug composed of corneocytes in the lower portion of the follicular infundibulum Infundibulum Uterus, Cervix, and Fallopian Tubes: Anatomy

• Open comedones Open Comedones Acne Vulgaris:
  • Commonly called “ blackheads Blackheads Acne Vulgaris”
  • Dilation and plugging at the follicular orifice on the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions surface
  • Contains brown or black keratotic material (due to oxidation of fatty acids Acids Chemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water. Acid-Base Balance)^[3]
  • < 5 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma
• Closed comedones Closed Comedones Acne Vulgaris:
  • Frequently called “ whiteheads Whiteheads Acne Vulgaris”
  • Plugging occurs at the follicular orifice below the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions surface.
  • Skin-colored, white, or gray papules
  • Smooth
  • < 5 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma
  • Precursor lesion to inflammatory acne Inflammatory Acne Acne Vulgaris

Inflammatory acne Inflammatory Acne Acne Vulgaris:

• Papulopustular acne Papulopustular Acne Acne Vulgaris:
  • < 5 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma
  • Superficial papules or pustules
  • Inflamed
• Nodular acne Nodular Acne Acne Vulgaris:
  • Tender
  • Inflamed
  • Much deeper
  • Typically ≥ 10 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma

Common locations^[2,7]

Where there are naturally higher concentrations of sebaceous glands:

• Face
• Neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess
• Upper chest
• Back
• Shoulders

Sequelae^[2,7]

• Postinflammatory hyperpigmentation Postinflammatory Hyperpigmentation Acne Vulgaris:
  • Results at the site of an active or resolving lesion
  • Increased risk in those with darker skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions pigmentation
  • Can persist for months
  • Resolves spontaneously
• Scarring Scarring Inflammation:
  • More likely to occur with inflammatory acne Inflammatory Acne Acne Vulgaris
  • Types:
    • Atrophic (“ice pick” or “boxcar” scars)
    • Hypertrophic
    • Keloids

Severe variants

The following variants are rare forms of acne that more often affect adolescent boys and men.

Acne fulminans Acne Fulminans Acne Vulgaris:^[7,12]

• Large, inflammatory, painful nodules
• Friable plaques with:
  • Erosions Erosions Corneal Abrasions, Erosion, and Ulcers
  • Ulcers
  • Hemorrhagic crusts
• Commonly occurs on the trunk
• Can be associated with systemic signs and symptoms:
  • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever
  • Malaise Malaise Tick-borne Encephalitis Virus
  • Arthralgias
  • Splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly
  • Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion nodosum
• May be induced by isotretinoin (which is also a treatment for acne fulminans Acne Fulminans Acne Vulgaris)

Acne conglobata Acne conglobata Severe and chronic form of acne characterized by large, burrowing abscesses associated with disfigurement. Acne Vulgaris:^[7,13]

• A severe form of nodular acne Nodular Acne Acne Vulgaris
• Aggregates of blackheads Blackheads Acne Vulgaris may be seen.
• Nodules coalesce to form sinus tracts (large, fluctuant Fluctuant Dermatologic Examination, linear lesions).
• May drain foul-smelling discharge
• Tender
• Large, irregular scars form.
• Increases in severity over time
• Common locations:
  • Back
  • Chest
  • Buttocks

Diagnosis

The diagnosis is clinical and based on the physical examination. No laboratory or skin biopsy Skin Biopsy Secondary Skin Lesions is required.

Clinical assessment^[4,5]

• No universally agreed-on grading Grading Methods which attempt to express in replicable terms the level of cell differentiation in neoplasms as increasing anaplasia correlates with the aggressiveness of the neoplasm. Grading, Staging, and Metastasis system
• Numerous validated options exist.
• Objective disease assessment:
  • Requires:
    • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions preparation (removal of facial hair and/or cosmetics)
    • Adequate lighting and patient positioning
  • Assessments may include:
    • Location of lesions
    • Types of lesions present
    • Lesion counts (typically for clinical trials, but less practical in day-to-day clinic encounters)
    • Qualitative descriptions (either globally and/or of individual lesions)
    • Presence/extent of scarring Scarring Inflammation
  • Some assessment tools include:
    • Investigator global assessment ( IGA IgA Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory iga is the main immunoglobulin in secretions. Immunoglobulins: Types and Functions)
    • Comprehensive Acne Severity System (CASS)
    • Leeds technique
    • Echelle de Cotation des Lésions d’Acné (ECLA; acne lesion scale Scale Dermatologic Examination score)
• Quality-of-life assessments:
  • Use validated questionnaires
  • Examples include:
    • Dermatology Life Quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement Index (DLQI)
    • Skindex-29 and Skindex-16
    • Assessment of the Psychological and Social Effects of Acne (APSEA)
    • Acne Quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of Life (AQOL) Scale Scale Dermatologic Examination
    • Acne-Specific Quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of Life Questionnaire (Acne-QoL)
  • Screening Screening Preoperative Care for depression/ anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder

Laboratory assessment^[4]

Typically not indicated; however, microbial testing (i.e., culture) and endocrinologic evaluation may be indicated in some cases.

• Culture:
  • Indicated in acne-like lesions that suggest a gram-negative folliculitis
  • Signs/symptoms that may warrant investigation include:
    • Uniform and eruptive pustules with rare nodules (typically in the setting of prolonged tetracycline Tetracycline A naphthacene antibiotic that inhibits amino Acyl tRNA binding during protein synthesis. Drug-Induced Liver Injury use)
    • Primarily in the perioral and perinasal areas
    • Lesions that are unresponsive to conventional acne treatments
• Endocrinologic evaluation: 
  • Indicated in individuals with features suggesting hyperandrogenism Hyperandrogenism A condition caused by the excessive secretion of androgens from the adrenal cortex; the ovaries; or the testes. The clinical significance in males is negligible. In women, the common manifestations are hirsutism and virilism as seen in patients with polycystic ovary syndrome and adrenocortical hyperfunction. Potassium-sparing Diuretics
  • Signs/symptoms suggesting hyperandrogenism Hyperandrogenism A condition caused by the excessive secretion of androgens from the adrenal cortex; the ovaries; or the testes. The clinical significance in males is negligible. In women, the common manifestations are hirsutism and virilism as seen in patients with polycystic ovary syndrome and adrenocortical hyperfunction. Potassium-sparing Diuretics in postpubertal females:
    • Hirsutism Hirsutism A condition observed in women and children when there is excess coarse body hair of an adult male distribution pattern, such as facial and chest areas. It is the result of elevated androgens from the ovaries, the adrenal glands, or exogenous sources. The concept does not include hypertrichosis, which is an androgen-independent excessive hair growth. Polycystic Ovarian Syndrome
    • Androgenic alopecia Alopecia Alopecia is the loss of hair in areas anywhere on the body where hair normally grows. Alopecia may be defined as scarring or non-scarring, localized or diffuse, congenital or acquired, reversible or permanent, or confined to the scalp or universal; however, alopecia is usually classified using the 1st 3 factors. Alopecia
    • Infrequent menses Menses The periodic shedding of the endometrium and associated menstrual bleeding in the menstrual cycle of humans and primates. Menstruation is due to the decline in circulating progesterone, and occurs at the late luteal phase when luteolysis of the corpus luteum takes place. Menstrual Cycle
    • Polycystic ovaries Ovaries Ovaries are the paired gonads of the female reproductive system that contain haploid gametes known as oocytes. The ovaries are located intraperitoneally in the pelvis, just posterior to the broad ligament, and are connected to the pelvic sidewall and to the uterus by ligaments. These organs function to secrete hormones (estrogen and progesterone) and to produce the female germ cells (oocytes). Ovaries: Anatomy
    • Clitoromegaly
  • Signs/symptoms suggesting hyperandrogenism Hyperandrogenism A condition caused by the excessive secretion of androgens from the adrenal cortex; the ovaries; or the testes. The clinical significance in males is negligible. In women, the common manifestations are hirsutism and virilism as seen in patients with polycystic ovary syndrome and adrenocortical hyperfunction. Potassium-sparing Diuretics in prepubertal children:
    • Early-onset body odor
    • Presence of sexual hair (axillary, pubic)
    • Advanced bone age Bone Age Short Stature in Children and/or accelerated growth
    • Genital maturation
  • Testing and interpretation is complex and is best done in consultation with a specialist.
  • Typical lab tests ordered during hyperandrogenism Hyperandrogenism A condition caused by the excessive secretion of androgens from the adrenal cortex; the ovaries; or the testes. The clinical significance in males is negligible. In women, the common manifestations are hirsutism and virilism as seen in patients with polycystic ovary syndrome and adrenocortical hyperfunction. Potassium-sparing Diuretics workup include:
    • Free and total testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens levels
    • Dehydroepiandrosterone Dehydroepiandrosterone A major C19 steroid produced by the adrenal cortex. It is also produced in small quantities in the testis and the ovary. Dehydroepiandrosterone (DHEA) can be converted to testosterone; androstenedione; estradiol; and estrone. Androgens and Antiandrogens sulfate (DHEA-S)
    • Androstenedione Androstenedione A delta-4 C19 steroid that is produced not only in the testis, but also in the ovary and the adrenal cortex. Depending on the tissue type, androstenedione can serve as a precursor to testosterone as well as estrone and estradiol. Androgens and Antiandrogens
    • Follicle-stimulating hormone ( FSH FSH A major gonadotropin secreted by the adenohypophysis. Follicle-stimulating hormone stimulates gametogenesis and the supporting cells such as the ovarian granulosa cells, the testicular sertoli cells, and leydig cells. Fsh consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle) and luteinizing hormone ( LH LH A major gonadotropin secreted by the adenohypophysis. Luteinizing hormone regulates steroid production by the interstitial cells of the testis and the ovary. The preovulatory luteinizing hormone surge in females induces ovulation, and subsequent luteinization of the follicle. Luteinizing hormone consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity. Menstrual Cycle)
    • Estrogen Estrogen Compounds that interact with estrogen receptors in target tissues to bring about the effects similar to those of estradiol. Estrogens stimulate the female reproductive organs, and the development of secondary female sex characteristics. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds. Ovaries: Anatomy
    • Sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria hormone-binding globulin ( SHBG SHBG A glycoprotein migrating as a beta-globulin. Its molecular weight, 52, 000 or 95, 000-115, 000, indicates that it exists as a dimer. The protein binds testosterone, dihydrotestosterone, and estradiol in the plasma. Sex hormone-binding protein has the same amino acid sequence as androgen-binding protein. They differ by their sites of synthesis and post-translational oligosaccharide modifications. Gonadal Hormones)
    • 17β-hydroxysteroids
    • Prolactin Prolactin A lactogenic hormone secreted by the adenohypophysis. It is a polypeptide of approximately 23 kd. Besides its major action on lactation, in some species prolactin exerts effects on reproduction, maternal behavior, fat metabolism, immunomodulation and osmoregulation. Breasts: Anatomy
    • Testing for insulin resistance Insulin resistance Diminished effectiveness of insulin in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent hyperglycemia or ketosis. Diabetes Mellitus

Management

Management may vary depending on practice location. The following information is based on US, UK, and European literature and guidelines.

Patient counseling^[6]

• Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions care:
  • Use gentle skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions cleansers.
  • Use non-comedogenic cosmetics and skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions care products, and remove them at the end of the day 
  • Avoid oil-based, comedogenic skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions products.
  • Avoid picking at lesions or aggressively scrubbing skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions.
• Patient education:
  • Acne vulgaris Acne vulgaris Acne vulgaris, also known as acne, is a common disorder of the pilosebaceous units in adolescents and young adults. The condition occurs due to follicular hyperkeratinization, excess sebum production, follicular colonization by Cutibacterium acnes, and inflammation. Acne Vulgaris is a long-term condition.
  • Improvement is often slow and requires consistency Consistency Dermatologic Examination with the treatment regimen.
  • Response to treatment regimens vary.
• Dietary changes:
  • Data are too limited for most organizations to recommend specific dietary changes.
  • Could consider reducing:
    • Milk/dairy
    • High glycemic index foods
  • Consider nutritional counseling if patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship plan on making significant dietary changes. 

Medical therapy for mild disease^[4,5]

Mild disease, including both mild papulopustular (inflammatory) and comedonal (noninflammatory) disease is typically treated with topical agents. 

Topical retinoids Retinoids Retinol and derivatives of retinol that play an essential role in metabolic functioning of the retina, the growth of and differentiation of epithelial tissue, the growth of bone, reproduction, and the immune response. Dietary vitamin A is derived from a variety of carotenoids found in plants. It is enriched in the liver, egg yolks, and the fat component of dairy products. Fat-soluble Vitamins and their Deficiencies:

• Normalizes follicular hyperproliferation and minimizes inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation
• Also helps with postinflammatory hyperpigmentation Postinflammatory Hyperpigmentation Acne Vulgaris
• Recommended as monotherapy for comedonal acne
• Should be used in combination with antibiotics in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with inflammatory acne Inflammatory Acne Acne Vulgaris lesions
• Options:
  • Adapalene 0.1%‒0.3% cream, lotion, or gel, applied once daily (preferred agent by the European Dermatologic Forum^[5]; can be applied directly with benzoyl peroxide Benzoyl peroxide A peroxide derivative that has been used topically for burns and as a dermatologic agent in the treatment of acne and poison ivy dermatitis. It is used also as a bleach in the food industry. Molluscum Contagiosum)
  • Tretinoin 0.025%‒0.1% cream or gel, apply to affected areas once daily (in the evenings; should be applied at a different time than benzoyl peroxide Benzoyl peroxide A peroxide derivative that has been used topically for burns and as a dermatologic agent in the treatment of acne and poison ivy dermatitis. It is used also as a bleach in the food industry. Molluscum Contagiosum application)
  • Tazarotene 0.05%‒0.1% cream or gel, applied once daily (in the evening); contraindicated in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
• Adverse effects:
  • Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions irritation and drying
  • Photosensitivity Photosensitivity Tetracyclines
  • Hyperpigmentation Hyperpigmentation Excessive pigmentation of the skin, usually as a result of increased epidermal or dermal melanin pigmentation, hypermelanosis. Hyperpigmentation can be localized or generalized. The condition may arise from exposure to light, chemicals or other substances, or from a primary metabolic imbalance. Malassezia Fungi or hypopigmentation Hypopigmentation A condition caused by a deficiency or a loss of melanin pigmentation in the epidermis, also known as hypomelanosis. Hypopigmentation can be localized or generalized, and may result from genetic defects, trauma, inflammation, or infections. Malassezia Fungi

Topical benzoyl peroxide Benzoyl peroxide A peroxide derivative that has been used topically for burns and as a dermatologic agent in the treatment of acne and poison ivy dermatitis. It is used also as a bleach in the food industry. Molluscum Contagiosum:

• Has antibacterial Antibacterial Penicillins and mild comedolytic properties
• May be used as monotherapy, or in combination with other topical or systemic agents
• Has properties that prevent bacterial resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing → recommended for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship on topical or systemic antibiotics
• Many variations in products:
  • Available as a topical wash, cream, gel, or foam
  • Concentrations range from 2.5% to 10%
  • Leave-on and wash-off preparations
  • Available in several combination products, the most common being:
    • Benzoyl peroxide Benzoyl peroxide A peroxide derivative that has been used topically for burns and as a dermatologic agent in the treatment of acne and poison ivy dermatitis. It is used also as a bleach in the food industry. Molluscum Contagiosum + adapalene
    • Benzoyl peroxide Benzoyl peroxide A peroxide derivative that has been used topically for burns and as a dermatologic agent in the treatment of acne and poison ivy dermatitis. It is used also as a bleach in the food industry. Molluscum Contagiosum + clindamycin Clindamycin An antibacterial agent that is a semisynthetic analog of lincomycin. Lincosamides
• Duration and efficacy:
  • Improvements typically seen within 5‒14 days after starting therapy
  • Maximum lesion reduction expected by 8‒12 weeks of use
  • Can be used long term as ongoing maintenance therapy
• May cause concentration-dependent irritation and staining/bleaching of fabric

Topical antibiotics:

• Primary action is to prevent new lesions (rather than treat current ones)
• Drugs accumulate in the follicles and exert both antibacterial Antibacterial Penicillins and antiinflammatory effects.
• Best used in combination with benzoyl peroxide Benzoyl peroxide A peroxide derivative that has been used topically for burns and as a dermatologic agent in the treatment of acne and poison ivy dermatitis. It is used also as a bleach in the food industry. Molluscum Contagiosum (multiple combination products available)
• Not used as monotherapy owing to antibiotic resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing
• Options:
  • Clindamycin Clindamycin An antibacterial agent that is a semisynthetic analog of lincomycin. Lincosamides 1% gel (preferred topical antibiotic) applied to the affected areas once or twice daily depending on formulation
  • Minocycline Minocycline A tetracycline analog, having a 7-dimethylamino and lacking the 5 methyl and hydroxyl groups, which is effective against tetracycline-resistant staphylococcus infections. Tetracyclines 4% foam applied to the affected area once daily
  • Erythromycin Erythromycin A bacteriostatic antibiotic macrolide produced by streptomyces erythreus. Erythromycin a is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50s ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. Macrolides and Ketolides 2% solution, ointment, or gel applied once or twice daily

Other agents:

• Salicylic acid 0.5%‒2%:
  • May be used as an alternative to topical retinoids Retinoids Retinol and derivatives of retinol that play an essential role in metabolic functioning of the retina, the growth of and differentiation of epithelial tissue, the growth of bone, reproduction, and the immune response. Dietary vitamin A is derived from a variety of carotenoids found in plants. It is enriched in the liver, egg yolks, and the fat component of dairy products. Fat-soluble Vitamins and their Deficiencies
  • Targets follicular hyperproliferation and abnormal desquamation Desquamation Staphylococcal Scalded Skin Syndrome (SSSS)
  • Apply 1‒3 times daily.
  • Has a cumulative irritative and drying effect
• Azelaic acid Azelaic Acid Acne Vulgaris 15%‒20%:
  • May also be used as an alternative to topical retinoids Retinoids Retinol and derivatives of retinol that play an essential role in metabolic functioning of the retina, the growth of and differentiation of epithelial tissue, the growth of bone, reproduction, and the immune response. Dietary vitamin A is derived from a variety of carotenoids found in plants. It is enriched in the liver, egg yolks, and the fat component of dairy products. Fat-soluble Vitamins and their Deficiencies
  • Comedolytic and antiinflammatory and has antibacterial Antibacterial Penicillins properties
  • Also helps with postinflammatory hyperpigmentation Postinflammatory Hyperpigmentation Acne Vulgaris
  • Generally safe in pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
  • Apply a thin film to the affected areas twice daily
• Dapsone Dapsone A sulfone active against a wide range of bacteria but mainly employed for its actions against Mycobacterium leprae. Its mechanism of action is probably similar to that of the sulfonamides which involves inhibition of folic acid synthesis in susceptible organisms. It is also used with pyrimethamine in the treatment of malaria. Antimycobacterial Drugs 5% gel:
  • A sulfone with antiinflammatory properties
  • Should not be applied at the same time as benzoyl peroxide Benzoyl peroxide A peroxide derivative that has been used topically for burns and as a dermatologic agent in the treatment of acne and poison ivy dermatitis. It is used also as a bleach in the food industry. Molluscum Contagiosum
  • Works best in adult females
  • Applied twice daily

Medical therapy for moderate and severe disease^[4-6]

Oral contraceptives and/or other antiandrogens Antiandrogens Antiandrogenic drugs decrease the effect of androgens. Classes include androgen receptor blockers, 5-alpha-reductase inhibitors, and androgen synthesis inhibitors. Both men and women may use antiandrogens, which treat advanced prostate cancer, benign prostatic hyperplasia (BPH), alopecia, and hirsutism. Androgens and Antiandrogens:

• Used in women
• Reduces androgen effects in order to minimize sebum Sebum The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. Infectious Folliculitis production
• Oral contraceptives:
  • May be used alone or in combination with other treatments
  • Dosing: take 1 tablet by mouth once daily
  • Androgenic effects of progestins Progestins Compounds that interact with progesterone receptors in target tissues to bring about the effects similar to those of progesterone. Primary actions of progestins, including natural and synthetic steroids, are on the uterus and the mammary gland in preparation for and in maintenance of pregnancy. Hormonal Contraceptives:
    • Drospirenone Drospirenone Hormonal Contraceptives is the only true anti-androgenic progestin.
    • Most progestins Progestins Compounds that interact with progesterone receptors in target tissues to bring about the effects similar to those of progesterone. Primary actions of progestins, including natural and synthetic steroids, are on the uterus and the mammary gland in preparation for and in maintenance of pregnancy. Hormonal Contraceptives are derived from testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens and have androgenic potential.
    • However, when combined with ethinyl estradiol Ethinyl estradiol A semisynthetic alkylated estradiol with a 17-alpha-ethinyl substitution. It has high estrogenic potency when administered orally, and is often used as the estrogenic component in oral contraceptives. Hormonal Contraceptives (EE), ovarian androgen production is suppressed and SHBG SHBG A glycoprotein migrating as a beta-globulin. Its molecular weight, 52, 000 or 95, 000-115, 000, indicates that it exists as a dimer. The protein binds testosterone, dihydrotestosterone, and estradiol in the plasma. Sex hormone-binding protein has the same amino acid sequence as androgen-binding protein. They differ by their sites of synthesis and post-translational oligosaccharide modifications. Gonadal Hormones (which binds up free testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens) is increased → overall effect is anti-androgenic
  • 4 FDA-approved contraceptive options approved to treat acne in the US:
    • EE/ drospirenone Drospirenone Hormonal Contraceptives
    • EE/ drospirenone Drospirenone Hormonal Contraceptives/levomefolate
    • EE/ norgestimate Norgestimate Hormonal Contraceptives
    • EE/ norethindrone Norethindrone A synthetic progestational hormone with actions similar to those of progesterone but functioning as a more potent inhibitor of ovulation. It has weak estrogenic and androgenic properties. The hormone has been used in treating amenorrhea, functional uterine bleeding, endometriosis, and for contraception. Noncontraceptive Estrogen and Progestins acetate/ferrous fumarate Fumarate Citric Acid Cycle
• Other antiandrogens Antiandrogens Antiandrogenic drugs decrease the effect of androgens. Classes include androgen receptor blockers, 5-alpha-reductase inhibitors, and androgen synthesis inhibitors. Both men and women may use antiandrogens, which treat advanced prostate cancer, benign prostatic hyperplasia (BPH), alopecia, and hirsutism. Androgens and Antiandrogens:^[4]
  • Spironolactone Spironolactone A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. Potassium-sparing Diuretics:
    • Aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors antagonist that also has antiandrogenic properties
    • ↓ Testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens production, as well as testosterone Testosterone A potent androgenic steroid and major product secreted by the leydig cells of the testis. Its production is stimulated by luteinizing hormone from the pituitary gland. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to dihydrotestosterone or estradiol. Androgens and Antiandrogens binding to skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors
    • Dosing: Start at 25‒50 mg/day in 1‒2 divided doses and titrate as needed up to a maximum of 100 mg twice daily; typical dose is 50‒100 mg/day
    • Use with care in combination with drospirenone Drospirenone Hormonal Contraceptives (a spironolactone Spironolactone A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. Potassium-sparing Diuretics analog) to avoid hyperkalemia Hyperkalemia Hyperkalemia is defined as a serum potassium (K+) concentration >5.2 mEq/L. Homeostatic mechanisms maintain the serum K+ concentration between 3.5 and 5.2 mEq/L, despite marked variation in dietary intake. Hyperkalemia can be due to a variety of causes, which include transcellular shifts, tissue breakdown, inadequate renal excretion, and drugs. Hyperkalemia.
  • Flutamide Flutamide An antiandrogen with about the same potency as cyproterone in rodent and canine species. Androgens and Antiandrogens:
    • Nonsteroidal selective androgen receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors blocker (typically used for prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. cancer)
    • Off-label dosing for acne per American Academy of Dermatology (AAD): 250‒500 mg once daily

Oral antibiotics:

• Recommended for individuals with moderate to severe inflammatory acne Inflammatory Acne Acne Vulgaris that is resistant to topical treatment alone
• Should be used in combination with a topical retinoid, azelaic acid Azelaic Acid Acne Vulgaris, and/or benzoyl peroxide Benzoyl peroxide A peroxide derivative that has been used topically for burns and as a dermatologic agent in the treatment of acne and poison ivy dermatitis. It is used also as a bleach in the food industry. Molluscum Contagiosum
• Duration of treatment:
  • Ideally limited to 3‒4 months to limit Limit A value (e.g., pressure or time) that should not be exceeded and which is specified by the operator to protect the lung Invasive Mechanical Ventilation the risk of resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing
  • Topical therapies should be continued as maintenance therapy after stopping systemic antibiotics 
• Tetracyclines Tetracyclines Tetracyclines are a class of broad-spectrum antibiotics indicated for a wide variety of bacterial infections. These medications bind the 30S ribosomal subunit to inhibit protein synthesis of bacteria. Tetracyclines cover gram-positive and gram-negative organisms, as well as atypical bacteria such as chlamydia, mycoplasma, spirochetes, and even protozoa. Tetracyclines (preferred):
  • Doxycycline immediate-release dosing options:
    • 50‒100 mg twice daily 
    • 100 mg once daily
    • 20 mg twice daily (sub-antimicrobial dosing)
  • Doxycycline delayed release:
    • 100 mg twice daily on day 1, then once daily
    • 40 mg once daily (sub-antimicrobial dosing)
  • Minocycline Minocycline A tetracycline analog, having a 7-dimethylamino and lacking the 5 methyl and hydroxyl groups, which is effective against tetracycline-resistant staphylococcus infections. Tetracyclines immediate release:
    • 50 mg 1‒3 times daily (AAD recommended dosing)
    • 50‒100 mg once or twice daily (typical dose, 100 mg twice daily)
  • Minocycline Minocycline A tetracycline analog, having a 7-dimethylamino and lacking the 5 methyl and hydroxyl groups, which is effective against tetracycline-resistant staphylococcus infections. Tetracyclines delayed release: approximately 1 mg/kg once daily, rounded to the nearest available dose (range, 45‒135 mg)
  • Tetracycline Tetracycline A naphthacene antibiotic that inhibits amino Acyl tRNA binding during protein synthesis. Drug-Induced Liver Injury 500 mg twice daily for 1‒2 weeks, then decrease to 125‒500 mg daily
• Macrolides Macrolides Macrolides and ketolides are antibiotics that inhibit bacterial protein synthesis by binding to the 50S ribosomal subunit and blocking transpeptidation. These antibiotics have a broad spectrum of antimicrobial activity but are best known for their coverage of atypical microorganisms. Macrolides and Ketolides (indicated in individuals who have contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation to tetracyclines Tetracyclines Tetracyclines are a class of broad-spectrum antibiotics indicated for a wide variety of bacterial infections. These medications bind the 30S ribosomal subunit to inhibit protein synthesis of bacteria. Tetracyclines cover gram-positive and gram-negative organisms, as well as atypical bacteria such as chlamydia, mycoplasma, spirochetes, and even protozoa. Tetracyclines, such as pregnant women and children < 8)
  • Erythromycin Erythromycin A bacteriostatic antibiotic macrolide produced by streptomyces erythreus. Erythromycin a is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50s ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. Macrolides and Ketolides 250‒500 mg twice daily
  • Azithromycin Azithromycin A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Macrolides and Ketolides pulse dosing:
    • 500 mg once daily for 4 consecutive days per month for 3 months
    • 500 mg once daily for 3 days the 1st week, then once weekly for 8 additional weeks
    • 500 mg once daily for 3 consecutive days each week in month 1, then 2 consecutive days each week in month 2, then 1 day per week in month 3
• Penicillins Penicillins Beta-lactam antibiotics contain a beta-lactam ring as a part of their chemical structure. Drugs in this class include penicillin G and V, penicillinase-sensitive and penicillinase-resistant penicillins, cephalosporins, carbapenems, and aztreonam. Penicillins or cephalosporins Cephalosporins Cephalosporins are a group of bactericidal beta-lactam antibiotics (similar to penicillins) that exert their effects by preventing bacteria from producing their cell walls, ultimately leading to cell death. Cephalosporins are categorized by generation and all drug names begin with “cef-” or “ceph-.” Cephalosporins (generally not recommended for acne treatment Acne Treatment Acne Vulgaris):
  • May be considered in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who:
    • Are pregnant and/or
    • Have allergies Allergies A medical specialty concerned with the hypersensitivity of the individual to foreign substances and protection from the resultant infection or disorder. Selective IgA Deficiency to other classes of antibiotics
  • Options noted by the AAD:
    • Amoxicillin Amoxicillin A broad-spectrum semisynthetic antibiotic similar to ampicillin except that its resistance to gastric acid permits higher serum levels with oral administration. Penicillins 250 mg twice daily up to 500 mg 3 times daily
    • Cephalexin 500 mg twice daily
• Trimethoprim Trimethoprim The sulfonamides are a class of antimicrobial drugs inhibiting folic acid synthesize in pathogens. The prototypical drug in the class is sulfamethoxazole. Although not technically sulfonamides, trimethoprim, dapsone, and pyrimethamine are also important antimicrobial agents inhibiting folic acid synthesis. The agents are often combined with sulfonamides, resulting in a synergistic effect. Sulfonamides and Trimethoprim– sulfamethoxazole Sulfamethoxazole A bacteriostatic antibacterial agent that interferes with folic acid synthesis in susceptible bacteria. Its broad spectrum of activity has been limited by the development of resistance. Sulfonamides and Trimethoprim (TMP-SMX) (generally not recommended for acne treatment Acne Treatment Acne Vulgaris) may be considered in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who:
  • Are unable to tolerate tetracyclines Tetracyclines Tetracyclines are a class of broad-spectrum antibiotics indicated for a wide variety of bacterial infections. These medications bind the 30S ribosomal subunit to inhibit protein synthesis of bacteria. Tetracyclines cover gram-positive and gram-negative organisms, as well as atypical bacteria such as chlamydia, mycoplasma, spirochetes, and even protozoa. Tetracyclines
  • Have resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing to other treatments

Isotretinoin:

• Targets all 4 pathogenic factors
• Indicated for severe or resistant acne (including acne fulminans Acne Fulminans Acne Vulgaris and acne conglobata Acne conglobata Severe and chronic form of acne characterized by large, burrowing abscesses associated with disfigurement. Acne Vulgaris)
• Dosing:
  • Typically started at 0.5 mg/kg/day in 2 divided doses for the 1st month, then increased up to 1.0 mg/kg/day in 1‒2 divided doses, as tolerated
  • Lower doses can be considered (as low as 0.1 mg/kg/day), and show some efficacy.
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship treated with higher doses (i.e., 1.0 mg/kg/day) have significantly lower relapse Relapse Relapsing Fever rates than those treated with 0.5 mg/kg/day (or less).
• Duration of therapy:
  • Until a cumulative dose of 120‒150 mg/kg is reached
  • Typically 15‒20 weeks
• Requires close monitoring due to the risk of:
  • Hyperlipidemia → monitor lipid profiles
  • Transaminitis Transaminitis Tick-borne Encephalitis Virus → monitor liver function tests Liver function tests Liver function tests, also known as hepatic function panels, are one of the most commonly performed screening blood tests. Such tests are also used to detect, evaluate, and monitor acute and chronic liver diseases. Liver Function Tests
  • Vision Vision Ophthalmic Exam changes
  • Teratogenic effects if patient becomes pregnant
• Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship must use 2 forms of contraception while on therapy and for 1 month post-therapy.

Intralesional corticosteroids Intralesional Corticosteroids Hypertrophic and Keloid Scars:

• Medication: triamcinolone Triamcinolone A glucocorticoid given, as the free alcohol or in esterified form, orally, intramuscularly, by local injection, by inhalation, or applied topically in the management of various disorders in which corticosteroids are indicated. Glucocorticoids acetonide 
• Indications:
  • Occasional “stubborn” inflammatory nodulocystic lesions
  • Acne keloidalis Acne keloidalis A type of acneiform disorder in which secondary pyogenic infection in and around pilosebaceous structures ends in keloidal scarring. It manifests as persistent folliculitis of the back of the neck associated with occlusion of the follicular orifices. It is most often encountered in black or Asian men. Hypertrophic and Keloid Scars
• Note: not an effective strategy for managing multiple lesions

Choosing an initial therapy^[5]

Indications for referral^[6]

• Individuals with acne fulminans Acne Fulminans Acne Vulgaris or acne conglobata Acne conglobata Severe and chronic form of acne characterized by large, burrowing abscesses associated with disfigurement. Acne Vulgaris
• Diagnostic uncertainty
• Mild to moderate acne that has not responded to 2 completed courses of treatment
• Moderate to severe acne that has not responded to previous treatment that contained an oral antibiotic
• Acne with scarring Scarring Inflammation or persistent pigment changes
• Acne leading to severe psychological distress

Complications and Prognosis

Complications^[1,2,4,7,14]

• Psychosocial impacts due to the appearance of the affected skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions:
  • Low self-esteem
  • Anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder and depression
• Folliculitis:
  • May develop with prolonged use of topical antibiotics
  • Often results from gram-negative organisms
• Morbihan disease Morbihan Disease Acne Vulgaris:
  • Rare
  • Soft tissue Soft Tissue Soft Tissue Abscess edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema and erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion of the face
• Acne fulminans Acne Fulminans Acne Vulgaris can occur from isotretinoin use (despite also being a treatment for the condition).

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas^[1,10]

• Acne vulgaris Acne vulgaris Acne vulgaris, also known as acne, is a common disorder of the pilosebaceous units in adolescents and young adults. The condition occurs due to follicular hyperkeratinization, excess sebum production, follicular colonization by Cutibacterium acnes, and inflammation. Acne Vulgaris is a long-term condition.
• Most cases will eventually clear spontaneously.
• In some patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship, acne may persist throughout adulthood.
• Overall, the prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas is good with treatment.

Differential Diagnosis

• Rosacea Rosacea Rosacea is a chronic inflammatory disease of the skin that is associated with capillary hyperreactivity. This condition is predominantly seen in middle-aged women, and is more common in fair-skinned patients. Rosacea: a chronic inflammatory disease of the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions associated with capillary hyperreactivity Capillary Hyperreactivity Rosacea, usually seen in middle-aged women. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with facial erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion, telangiectasia Telangiectasia Permanent dilation of preexisting blood vessels creating small focal red lesions, most commonly in the skin or mucous membranes. It is characterized by the prominence of skin blood vessels, such as vascular spiders. Chronic Venous Insufficiency, papules, pustules, and phymatous changes. The absence of comedones Comedones Acne Vulgaris distinguishes rosacea Rosacea Rosacea is a chronic inflammatory disease of the skin that is associated with capillary hyperreactivity. This condition is predominantly seen in middle-aged women, and is more common in fair-skinned patients. Rosacea from acne vulgaris Acne vulgaris Acne vulgaris, also known as acne, is a common disorder of the pilosebaceous units in adolescents and young adults. The condition occurs due to follicular hyperkeratinization, excess sebum production, follicular colonization by Cutibacterium acnes, and inflammation. Acne Vulgaris. The diagnosis is clinical, and management involves avoiding triggers, gentle skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions care, topical and/or oral antibiotics, and laser or surgical therapies.
• Folliculitis: a common skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions condition characterized by inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation of hair follicles due to an infectious agent (most commonly Staphylococcus aureus Staphylococcus aureus Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications. Brain Abscess). Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with pruritus Pruritus An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. Atopic Dermatitis (Eczema), follicular pustules, and erythematous papules. There are no comedones Comedones Acne Vulgaris. The diagnosis is clinical. Management is generally supportive but may involve topical or oral antibiotics for severe cases.
• Hidradenitis suppurativa Hidradenitis suppurativa Hidradenitis suppurativa (HS) is a chronic skin condition due to the inflammation of apocrine sweat glands and hair follicles. Most commonly, it occurs due to occlusion of the follicular component of pilosebaceous units (PSUs). Hidradenitis Suppurativa: a chronic inflammatory condition of the hair follicle Hair follicle A tube-like invagination of the epidermis from which the hair shaft develops and into which sebaceous glands open. The hair follicle is lined by a cellular inner and outer root sheath of epidermal origin and is invested with a fibrous sheath derived from the dermis. Follicles of very long hairs extend into the subcutaneous layer of tissue under the skin. Cowden Syndrome and associated structures. The condition leads to follicular occlusion and rupture, which in turn, causes abscesses, sinus tracts, and scarring Scarring Inflammation. The disease commonly occurs in axillary, groin Groin The external junctural region between the lower part of the abdomen and the thigh. Male Genitourinary Examination, and inframammary regions. The diagnosis is clinical. Management is based on severity and can include topical or oral antibiotics, intralesional corticosteroids Intralesional Corticosteroids Hypertrophic and Keloid Scars, oral retinoids Retinoids Retinol and derivatives of retinol that play an essential role in metabolic functioning of the retina, the growth of and differentiation of epithelial tissue, the growth of bone, reproduction, and the immune response. Dietary vitamin A is derived from a variety of carotenoids found in plants. It is enriched in the liver, egg yolks, and the fat component of dairy products. Fat-soluble Vitamins and their Deficiencies, debridement Debridement The removal of foreign material and devitalized or contaminated tissue from or adjacent to a traumatic or infected lesion until surrounding healthy tissue is exposed. Stevens-Johnson Syndrome or surgical excision, and immunosuppressive medications.
• Keratosis pilaris Keratosis Pilaris Ichthyosis Vulgaris: a common condition that causes small, pointed, follicular papules on the extensor surfaces of the upper arms or thighs secondary to keratinization. Erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion may be present. The diagnosis is clinical. Management is unnecessary, but salicylic acid and retinoids Retinoids Retinol and derivatives of retinol that play an essential role in metabolic functioning of the retina, the growth of and differentiation of epithelial tissue, the growth of bone, reproduction, and the immune response. Dietary vitamin A is derived from a variety of carotenoids found in plants. It is enriched in the liver, egg yolks, and the fat component of dairy products. Fat-soluble Vitamins and their Deficiencies may be used.
• Periorificial dermatitis Dermatitis Any inflammation of the skin. Atopic Dermatitis (Eczema): a condition that causes an erythematous, papulopustular eruption that starts at the nasolabial folds and spreads periorally. Comedones Comedones Acne Vulgaris are not present. The diagnosis is clinical. Management involves avoiding causative agents (such as steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors or fluoride Fluoride Inorganic salts of hydrofluoric acid, hf, in which the fluorine atom is in the -1 oxidation state. Sodium and stannous salts are commonly used in dentifrices. Trace Elements) and topical or oral antibiotics.

Sebaceous hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation: a common condition caused by enlargement of sebaceous glands. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with a history of “oily skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions” may develop umbilicated, skin-colored, or yellowish papules, frequently involving the forehead Forehead The part of the face above the eyes. Melasma, nose Nose The nose is the human body’s primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Nose Anatomy (External & Internal), and cheeks Cheeks The part of the face that is below the eye and to the side of the nose and mouth. Melasma. The diagnosis is clinical, although biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma may be performed to rule out basal cell Basal Cell Erythema Multiforme carcinoma (owing to its similar appearance). Management is not necessary, but dermabrasion Dermabrasion The mechanical planing of the skin with sandpaper, emery paper, or wire brushes, to promote reepithelialization and smoothing of skin disfigured by acne scars or dermal nevi. Actinic Keratosis, laser therapy Laser Therapy The use of photothermal effects of lasers to coagulate, incise, vaporize, resect, dissect, or resurface tissue. Glaucoma, isotretinoin, or surgical removal may be done for cosmetic reasons.