10.4 From Notes - Acne Vulgaris: Causes, Development, and Treatment

Acne Vulgaris

• The most common skin disease, affecting 85% of people aged 12-25.
• Onset can occur at a younger age, potentially linked to earlier puberty.
• Genetic susceptibility plays a role.
• Incidence is similar in both sexes, but severe disease is more common in males.
• Develops in pilosebaceous units, primarily on the face, upper chest, and back.
• These follicles have large sebaceous glands, small vellus hairs, and dilated follicular canals.
• Lesions result from follicle obstruction, which can be noninflammatory (open and closed comedones) or inflammatory (papules, pustules, cystic nodules).
• Rupture of closed comedones leads to inflammation, potentially causing scarring.
• Follicular proliferation of Propionibacterium acnes (P. acnes) is a principal contributing factor .
• Hyperkeratinization of follicular epithelium is another factor.
• Excessive sebum production contributes, as androgens increase sebaceous gland size and productivity.
• Inflammation and follicle rupture occur due to accumulated debris and bacteria.
• P. acnes produces proinflammatory molecules and enzymes that break down triglycerides into free fatty acids (FFAs), leading to inflammation.
• Increased sebum feeds bacterial growth.
• Acne can be associated with polycystic ovarian syndrome, congenital adrenal hyperplasia, and endocrine tumors due to higher androgen levels.
• Individualized treatment may include combinations of topical retinoids, benzoyl peroxide, and antimicrobial agents.
• Retinoids target comedogenesis, P. acnes, inflammation, and sebum production.
• Benzoyl peroxide and topical antibiotics target comedogenesis, P. acnes, and inflammation.
• Combined oral contraceptives can benefit both inflammatory and noninflammatory acne.
• Systemic therapies (oral antibiotics, sex hormones, corticosteroids, isotretinoin) have potential side effects.
• Isotretinoin requires pregnancy prevention.
• Acne surgery (comedo extraction, intralesional steroids, cryosurgery) is used in selected cases.
• Severe scarring can be treated with dermabrasion, lasers, and resurfacing.
• Psychologic support is important due to the negative impact on quality of life, self-esteem, and mood, and its association with anxiety, depression, and suicidal ideation.
• Special consideration is needed for individuals with darker skin due to a greater risk of hyperpigmentation and keloidal scarring.
• Research continues on new drugs, vaccines, and immunotherapies against P. acnes.
• Acne conglobata is a severe, inflammatory form with communicating cysts and abscesses that can cause scarring and requires systemic and combination therapies.

Atopic Dermatitis (AD)

• Also known as atopic eczema.
• It is the most common cause of eczema in children, with a prevalence of approximately 25% in children and 2-3% in adults.
• Onset is usually between 2 and 6 months of age, with most cases within the first 5 years.
• More than half of individuals with AD develop asthma and allergies later in life.
• Positive skin tests to common food and inhalant allergens are seen in about 80%.
• Cause is not fully understood but involves an interplay of genetic predisposition, altered skin barrier function, altered innate immunity, and altered immune responses.
• "Inside-out" (immunologic dysregulation leading to barrier abnormality) and "outside-in" (primary barrier dysfunction causing immunologic perturbations) mechanisms are involved.
• In AD, memory T cells express cutaneous lymphocyte antigen (CLA), leading to lymphocyte homing to the skin.
• Inflammation involves activation of a Th2 phenotype, switching to Th1 in chronic phases, and release of cytokines, chemokines, IFN-γ, and GM-CSF.
• Mast cells, eosinophils, macrophages, and IgE-mediated autoreactivity contribute to inflammation.
• Filaggrin deficiency impairs the epidermal barrier, causing transepidermal water loss and easy penetration of pathogens and allergens, leading to a systemic hyperactive immune response.
• Keratinocytes are deficient in toll-like antimicrobial peptides, predisposing to colonization and infection with Staphylococcus aureus, viruses, and fungi.
• Alterations in the skin microbiome may also promote pathogenic colonization.
• Clinical features include frequent exacerbations, severe pruritus, redness, edema, and scaling.
• The skin becomes dry, sensitive, itchy, and easily irritated due to impaired barrier function, with microscopic cracks exacerbating inflammation, drying, and cracking.
• Itching is a hallmark symptom, and scratching leads to many clinical skin changes.
• In young children, the rash is primarily on the face, scalp, trunk, and extensor surfaces.
• In older children and adults, it tends to be on the neck, flexural creases, and hands and feet.
• Lichenification (thickening of the epidermis) is more common in adults with chronic eczema.
• There are no specific diagnostic laboratory features.
• Increased serum IgE, interleukin-4 and -13, eosinophils, and positive allergy skin tests are common.
• Management includes accurate diagnosis, evaluation of triggers and treatment response, managing confounding factors, and patient/caregiver education.
• Avoiding triggers and promoting skin hydration with emollients and mild cleansers are key.
• Bleach baths may help with recurrent infection.
• Anti-inflammatory agents like topical corticosteroids and calcineurin inhibitors are necessary for acute treatment and flares.
• Wet wrap therapy is used for severe eczema.
• Systemic steroids should generally be avoided due to potential adverse effects.
• Systemic therapy may include immunomodulators, sedating antihistamines, antibiotics, and phototherapy.
• Research aims to develop molecule-specific targets for long-term remission.

Diaper Dermatitis

• An irritant contact dermatitis caused by prolonged exposure to urine ammonia and feces, maceration, and friction from wet diapers or airtight covers.
• Lesions range from mild erythema to erythematous papular lesions.
• Secondary infection with Candida albicans is common, presenting as very erythematous with sharp margins and pustulovesicular satellite lesions.
• Disposable diapers have reduced its incidence.
• Treatment involves frequent diaper changes, air exposure, super-absorbent diapers, and topical protection with petrolatum or zinc oxide.
• Topical antifungals are used for C. albicans infection.

Infections of the Skin

• Breaks in skin integrity can cause or worsen infections.
• Most are superficial, but systemic signs can occur, especially in immunosuppressed children.
• Bacterial, viral, and fungal infections are major forms of skin disease.

Bacterial Infections

• Impetigo Contagiosum is common in infants and children aged 2-5 years, caused by Staphylococcus aureus (S. aureus) and less commonly Streptococcus pyogenes.
• Transmission is by direct and indirect contact, more common in warm, humid climates and crowded conditions.
• Predisposing factors include anemia and malnutrition.
• Bacterial invasion occurs through minor skin breaks or as a secondary infection.
• S. aureus produces exfoliative toxins (ETs) causing blister formation.
• Two types: nonbullous and bullous (caused only by S. aureus).
• Both begin as vesicles that rupture to form a honey-colored crust.
• Lesions are common on the face (around nose and mouth), hands, and exposed areas.
• Vesicular impetigo (nonbullous) is highly contagious, caused by Streptococcus pyogenes (alone or with S. aureus), and presents with small vesicles and honey-colored crusts.
• Untreated lesions can spread, and regional lymphadenitis is common.
• A significant complication is acute glomerulonephritis.
• Bullous impetigo, caused by S. aureus and its exfoliative toxin, is highly contagious and occurs in neonates.
• It presents with vesicles enlarging into superficial bullae, forming thin, flat, honey-colored crusts upon rupture.
• Treatment for uncomplicated lesions is topical mupirocin and fusidic acid.
• Extensive or complicated cases may require systemic antibiotics, avoiding β-lactams if MRSA is suspected.
• Prompt treatment prevents complications.
• Good handwashing and isolating infected items are important for prevention.
• Staphylococcal Scalded-Skin Syndrome (SSSS) is a serious staphylococcal infection in children under 5 years.
• Caused by group II staphylococci producing an exfoliative toxin that attacks desmoglein, causing skin separation below the granular layer of the epidermis.
• Toxins are produced elsewhere in the body and reach the skin via circulation; staphylococci are usually not found in the lesions.
• Neonates are at highest risk due to lack of immunity.
• Symptoms begin with fever, malaise, rhinorrhea, and irritability, followed by generalized erythema with skin tenderness.
• Impetigo may be associated.
• Erythema spreads to cover the body, sparing palms, soles, and mucous membranes.
• Within 24-48 hours, blisters and bullae may develop.
• Pain is severe, and fluid loss can cause dehydration.
• Perioral and nasolabial crusting occurs.
• Skin may slough in severe cases, healing in 10-14 days without scarring if secondary infection is prevented.
• Diagnosis requires culture and histology/cytology to differentiate from Stevens-Johnson syndrome and toxic epidermal necrolysis.
• Treatment involves oral or intravenous antibiotics, maintaining fluid balance, and aseptic skin care similar to severe burns.
• Topical antibiotics are ineffective.

Fungal Infections (Mycoses)

• Often caused by dermatophytes (tinea or ringworm) that thrive on keratin.
• Classified by body location.
• Epidermophyton is a major cause of superficial infections in children, invading the stratum corneum.
• The inflammatory response is cell-mediated.
• Tinea pedis (foot) is rare in prepubertal children; scaling is usually eczema.
• Tinea capitis (scalp ringworm) is the most common fungal infection in childhood, rarely affecting infants, seen in children 2-10 years.
• Primarily caused by Trichophyton tonsurans (T. tonsurans), also by Microsporum canis (M. canis) from cats, dogs, and rodents.
• Humans are terminal hosts for M. canis.
• T. tonsurans spreads directly between humans, especially in crowded areas.
• Asymptomatic carriers among household contacts are common.
• Lesions are often circular with broken hairs 1-3 mm above the scalp, causing partial alopecia (1-5 cm diameter).
• Slight erythema and scaling with raised borders may be present.
• Diagnosis by KOH examination and fungal culture.
• Wood light is less popular.
• Systemic treatment is always required as topical agents don't penetrate hair follicles.
• Griseofulvin is a common treatment; terbinafine, itraconazole, and fluconazole are alternatives.
• Tinea corporis (ringworm) is a common superficial dermatophyte infection, commonly caused by M. canis and Trichophyton mentagrophytes, often from contact with kittens and puppies.
• Affects nonhairy parts of the face, trunk, and limbs.
• Lesions are erythematous, round/oval scaling patches spreading peripherally with central clearing, creating a ring.
• Lesions are usually asymmetrical and multiple may overlap.
• Transmission by direct contact with infected lesions or indirect contact with personal items.
• Diagnosis by KOH examination of scale from the border.
• Most lesions respond to topical antifungal medications.
• Thrush describes Candida albicans (C. albicans) in the mouth mucous membranes of infants, less common in non-immunocompromised adults.
• C. albicans penetrates the epidermal barrier more easily due to keratolytic proteases.
• Characterized by white plaques/spots in the mouth leading to shallow ulcers.
• The tongue may have a dense white covering.
• Underlying mucosa is red and tender and may bleed.
• Fever and gastrointestinal irritation may occur, and infection can spread to the groin, buttocks, etc.
• Diagnosis is clinical but may include microscopy.
• Treatment can be difficult, including oral antifungal washes (e.g., nystatin).
• Treating Candida nipple infection/vaginitis in the mother and sterilizing feeding items can help prevent reinfection.

Viral Infections

• Caused by poxvirus, papovavirus, and herpesvirus.
• Molluscum Contagiosum is a common, highly contagious poxvirus infection of the epidermis, affecting school-aged children and sexually active young adults.
• Can be more severe/prolonged in atopic dermatitis and immunodeficiency (including AIDS).
• Transmitted by skin-to-skin contact, autoinoculation, and fomites.
• The virus induces epidermal cell proliferation and blocks immune responses, forming saccules with virus clusters.
• Lesions are discrete, slightly umbilicated, dome-shaped, waxy/pearl-like papules (1-5 mm) anywhere on skin/conjunctiva.
• In children, mainly on trunk, face, and extremities.
• Inflammation is usually absent unless traumatized or secondarily infected.
• Scarring may occur.
• Diagnosis by visual inspection (dermoscopy, confocal microscopy), stained smears of expressed material, biopsy, cell culture inoculation, or PCR.
• Most lesions self-resolve in 6-9 months without manipulation, but can take 2-4 years with manipulation.
• Treatment options include immunomodulatory/antiviral therapy and destructive procedures (cryotherapy, curettage, laser ablation), but no universally effective treatment exists.
• Cantharidin is commonly used.
• Treatment is recommended for genital lesions to prevent spread.
• Destructive therapy is poorly tolerated by children.
• Recurrences are common.
• Rubella (German or 3-Day Measles) is a common communicable disease of children and young adults caused by an RNA virus entering via the respiratory route.
• Mild in most children.
• Incubation 14-21 days.
• Prodromal symptoms may include enlarged cervical/postauricular lymph nodes, low-grade fever, headache, sore throat, runny nose, cough.
• A faint pink-to-red maculopapular rash develops on the face, spreading to trunk/extremities (sparing palms/soles) 1-4 days after initial symptoms.
• The rash subsides after 2-3 days, usually without complications.
• Children are generally not contagious after rash development.
• Vaccination (MMR) is effective, leading to near elimination in the US.
• Challenges to maintaining elimination include outbreaks in traveled countries, international travel, and unvaccinated individuals.
• Rubella virus is a candidate for global eradication.
• Women of childbearing age are immunized if their titer is low, and pregnancy should be avoided for 3 months post-vaccination.
• Accidental vaccination during pregnancy is not known to cause complications.
• No specific treatment; recovery is spontaneous.
• Supportive therapy includes rest, fluids, and vaporizer.
• Rare complications include mild encephalitis or peripheral neuritis.
• Rubeola (Red Measles) is a highly contagious acute viral disease of children, transmitted by direct contact with droplets of an RNA paramyxovirus.
• Incubation 7-12 days without symptoms.
• Virus enters the respiratory tract,attaches to dendritic cells and macrophages, amplifies in lymph tissue, and progresses to systemic disease.
• Prodromal symptoms include high fever, malaise, enlarged lymph nodes, runny nose, conjunctivitis, and barking cough.
• An erythematous maculopapular rash develops on the head, spreading distally over trunk, extremities, hands, and feet within 3-4 days.
• Early lesions blanch, followed by a brownish hue.
• Koplik spots (pinpoint white spots with red rings) develop on buccal mucosa 1-2 days before the rash.
• Rash subsides in 3-5 days.
• Complications can be from the primary infection or secondary bacterial infection, including measles encephalitis, otitis media, and pneumonia.
• Prevented by vaccination, but suboptimal delivery and refusal hinder eradication.
• Postexposure prophylaxis with antivirals complements vaccination.
• No specific treatment; supportive care as for rubella.
• Antibiotics for secondary bacterial infections.
• Roseola (Exanthema Subitum or 6th Disease) is caused by human herpesviruses 6 or 7 in infants 6 months to 2 years (up to 4 years).
• Incubation 5-15 days, followed by sudden onset of high fever for 3-5 days.
• After fever, an erythematous, nonpruritic macular rash (24-48 hours) develops, mainly on trunk, neck, and arms.
• Children usually feel well with few other symptoms.
• Usually no treatment is needed, and there are no complications.
• Chickenpox (Varicella) and Herpes Zoster (Shingles) are caused by varicella-zoster virus (VZV), a DNA herpes virus.
• Incubation 10-27 days (average 14).
• Vesicular lesions in the epidermis due to infection of keratinocytes.
• Vesicles rupture, followed by crusting or transient mucous membrane ulcers.
• Varicella occurs in those not previously exposed, while zoster occurs in those with past varicella, where the virus remains latent in dorsal root ganglia.
• Live attenuated VZV vaccine since 1995 has significantly reduced varicella incidence and complications.
• Chickenpox is common in early childhood (90% by age 10) and highly contagious via person-to-person contact and airborne droplets.
• Children are contagious at least 1 day before rash until 5-6 days after the first lesions in healthy children (longer in immunocompromised).
• Healthy children have no prodromal symptoms; the first sign may be itching or vesicles on the trunk, scalp, or face, later spreading to extremities.
• Lesions are in various stages (macules, papules, vesicles) simultaneously.
• Vesicles are superficial and easily ruptured, with new lesions erupting for 4-5 days (around 100-300 total).
• Vesicles become crusted.
• Fever usually lasts 2-3 days.
• Complications are rare in children but more common in adults.
• One case usually provides near-complete immunity.
• Maternal varicella-zoster immunoglobulin can modify disease progression if given before rash.
• Uncomplicated chickenpox requires no specific therapy.
• Baths, wet dressings, and oral antihistamines may help with itching and prevent secondary infection.
• Oral antistaphylococcal drugs for secondary bacterial infection.
• Prophylactic acyclovir may be valuable in immunosuppressed children.
• The varicella vaccine protects against both varicella and zoster, but vaccine-resistant viruses are a threat.
• Hand, Foot, and Mouth Disease (HFMD) is a contagious viral disease primarily of infants and young children, commonly caused by coxsackievirus A16 (CV-A16) and enterovirus 71 (EV-A71).
• Manifests as fever, vesicular ulcerous lesions in the mouth, and vesicular rashes on hands, feet, and buttocks.
• Some children may have severe complications (meningitis, encephalitis, paralysis, neurorespiratory syndrome).
• The disease is self-limiting with supportive care; vaccine research is ongoing.
• Herpes Zoster (Shingles) mainly occurs in adults, but about 5% of cases are in children under 15 years.
• Smallpox (Variola) is a highly contagious and deadly but preventable disease caused by poxvirus variolae.
• Eradicated worldwide in 1977; routine vaccination discontinued in the US in 1972.
• New vaccine (ACAM2000) exists for the US Strategic National Stockpile.

Insect Bites and Parasites

• Common causes of skin disorders in children and adults.
• Damage from trauma, allergic reactions, disease transmission, injection of substances, and inflammatory reactions.
• Scabies and pediculosis are common parasitic infections.

Scabies

• A contagious disease caused by the itch mite, Sarcoptes scabiei.
• Common in tropical settings, affecting many children.
• Transmitted by personal contact and infected clothing/linens.
• Often epidemic in overcrowded areas with poor sanitation or in long-term care.
• Mites have mechanisms to overcome host defenses.
• Immunocompromised individuals are at higher risk.
• Scabies can facilitate Streptococcus pyogenes and Staphylococcus aureus skin infections.
• Infestation begins with a female mite tunneling into the stratum corneum, depositing eggs and creating a burrow.
• Eggs mature into adults in 3 weeks.
• Primary lesions are burrows (2-15 mm), papules, and vesicular lesions with severe itching worsening at night.
• Two or three bites in a line ("breakfast, lunch, and dinner") may appear on exposed skin.
• Pruritus is a type IV sensitivity reaction to the mite and its products.
• First symptoms appear 3-5 weeks after primary infestation, 1-2 days after reinfestation.
• In older children and adults, lesions are in finger webs, axillae, wrist creases, belt line, nipples, genitalia, and lower buttocks.
• Infants and young children have involvement of palms, soles, head, back, neck, and face.
• Secondary infections and crusting can occur from scratching.
• Diagnosis by observing tunnels/burrows and microscopic examination of skin scrapings for mites, eggs, or feces.
• Treatment involves topical scabicides or oral ivermectin, which is curative.
• Pruritus may persist for 10+ days after treatment.
• All clothing and linens should be washed/dried in hot cycles or dry-cleaned.

Pediculosis (Lice Infestation)

• Has three types: head louse (Pediculus capitis - most common), body louse (Pediculus corporis), and pubic/crab louse (Phthirus pubis).
• Highly contagious blood-sucking parasites.
• Female louse lives about a month and lays 7-10 eggs (nits) daily, mating every 3-4 weeks.
• Mouthparts pierce and suck blood, secreting toxic saliva causing pruritic dermatitis.
• Head/body lice spread by direct personal contact or indirectly by sharing combs, brushes, towels, infested clothes/toys/furniture/bedding.
• Crab lice spread by body contact, such as with an infected adult, or sharing clothing/headphones.
• Pruritus is the major symptom.
• Head lice ova attach to hairs above the ears and occipital region.
• Body louse primary lesion is a pinpoint red macule/papule/wheal with a hemorrhagic puncture site, often masked by excoriations.
• Crab lice are found on pubic hairs but can involve other body hair including eyelashes.
• Young children may have crab lice on eyebrows/eyelashes.
• Live lice (2-3 mm) are rarely seen, but ova (nits) are visible as oval, yellowish pinpoint specks attached to hair shafts.
• Ova fluoresce under UV light (Wood lamp) and are best seen microscopically.
• Treatment with topical pediculicides (e.g., permethrin) or oral ivermectin.
• Head/pubic lice can be treated with wet combing every 3 days for 2 weeks to remove nits (less effective).
• All clothes, towels, bedding, combs, and brushes should be hot washed/dried or boiled/ironed.
• Individuals with personal contact should also be treated.

Fleas

• Wingless, jumping blood-feeding insects (cat, dog, human fleas common).
• Young children are very susceptible.
• Bites occur in clusters along arms/legs or where clothing is tight, producing an urticarial wheal with a central hemorrhagic puncture.
• Flea bites can transmit plague, tularemia, and cat-scratch disease.
• Treatment includes spraying carpets/crevices/furniture with insecticides (malathion or lindane powder), treating infected animals, and hot washing bedding/clothes.

Bedbugs (Cimex lectularius)

• Blood-sucking parasites in crevices/cracks of floors, walls, furniture, and bedding.
• Reddish brown, 3-5 mm long, nocturnal, feeding for 5-15 minutes.
• Attracted by warmth and CO2, can travel long distances.
• Immunologic reactions to saliva vary; bites typically yield erythematous and pruritic papules.
• Face and distal extremities are preferentially involved.
• If not previously sensitized, only a red macule to nodule (lasting up to 14 days) may develop
• Sensitized individuals may form pruritic wheals, papules, and vesicles; rarely, anemia and angioedema.
• Most lesions respond to antihistamines/corticosteroids.
• Secondary infections need antibiotics.
• Elimination involves inspecting/cleaning/disposing of contaminated items and using approved insecticides (often by a professional).

Cutaneous Hemangiomas and Vascular Malformations

• Frequent tumors of early infancy, categorized as vascular tumors (hemangiomas) or vascular malformations.

Cutaneous Hemangiomas

• Benign tumors from rapid growth of vascular endothelial cells, forming extra blood vessels.
• Can be superficial (infantile/capillary/strawberry) or deep (cavernous/congenital).
• Etiology may involve embolization of fetal placental endothelial cells or loss of placental angiogenic inhibitor.
• Superficial hemangiomas are associated with endothelial glucose transporter 1 (GLUT1).
• Mast cell proliferation is thought to promote angiogenesis.
• Fibrosis and a rich vascular network give a firm, rubbery feel.
• More common in females.
• About 30% are present at birth, usually emerging in the first few weeks.
• They grow rapidly in the first few years, becoming bright red, elevated with minute capillaries (strawberry appearance).
• Usually a single lesion on the head/neck or trunk.
• After initial growth, they grow with the child and then start to involute at 12-16 months.
• Approximately 90% involute by 5-9 years without scarring.
• Most superficial hemangiomas need no treatment.
• Treatment may be required for lesions over the eye, ear, nose, mouth, urethra, or anus due to functional interference or risk of infection/injury.
• Cavernous hemangiomas are a rare GLUT1-negative variant, fully grown solitary lesions at birth, primarily on head, neck, or limbs.
• Appear as spongy purplish masses with mature, larger vessels.
• Two groups: rapidly involuting (disappear by 12-14 months, leaving thin skin) and noninvoluting.
• Rapidly progressing hemangiomas are treated with beta-blockers (e.g., propranolol) as first-line agents, with regression within 2 weeks.
• Other therapies include systemic/intralesional steroids, cryosurgery, laser surgery, sclerotherapy, and embolization.
• Interferons, vincristine, cyclophosphamide, and radiotherapy can suppress angiogenesis.

Cutaneous Vascular Malformations

• Rare congenital anomalies of blood vessels present at birth but may not be apparent for years.
• Grow proportionately with the child and never regress.
• Equal in males/females.
• May expand rapidly during hormonal changes or trauma.
• Classified as low flow (capillaries, veins, lymphatics) or high flow (arteriovenous).
• Can involve other areas (GI tract, bone, eye, brain - Maffucci syndrome, Sturge-Weber syndrome, blue rubber bleb nevus syndrome)
• Overgrowth syndromes can occur.
• The most common are nevus flammeus (port-wine stain) and salmon patches.