Viral, Fungal and Parasitic Skin Infections

Herpes Simplex and Varicella-Zoster

Herpes Simplex Virus: HSV-1 and HSV-2

Herpes simplex viruses are enveloped, linear double-stranded DNA viruses in the Herpesviridae family. HSV-1 and HSV-2 are alpha-herpesviruses, characterized by rapid lytic replication in epithelial cells and lifelong latency in sensory neurons. HSV-1 classically causes oral lesions and encephalitis; HSV-2 classically causes genital disease and neonatal herpes, although either type can infect either site.

After entry through mucosa or abraded skin, HSV replicates locally, producing painful grouped vesicles on an erythematous base. Viral particles then travel by retrograde axonal transport to sensory ganglia: HSV-1 commonly to the trigeminal ganglion, HSV-2 to the sacral dorsal root ganglia. Reactivation occurs with fever, ultraviolet light, stress, menstruation, immunosuppression, or local trauma, followed by anterograde transport back to skin or mucosa.

Feature	HSV-1	HSV-2
Typical site	Orolabial mucosa; trigeminal latency	Genital mucosa; sacral latency
Classic disease	Herpes labialis, gingivostomatitis, keratitis, temporal lobe encephalitis	Genital herpes, neonatal herpes, aseptic meningitis
Transmission	Saliva, oral contact	Sexual contact, vertical transmission during delivery
Recurrence	Common oral recurrence	More frequent genital recurrence

Primary HSV infection may be asymptomatic or severe. Primary herpetic gingivostomatitis causes fever, painful oral ulcers, and cervical lymphadenopathy. Herpes labialis presents as recurrent “cold sores” at the vermilion border. Genital herpes causes painful vesicles or ulcers, dysuria, tender inguinal nodes, and systemic symptoms in primary infection. Herpetic whitlow involves painful vesicles on the finger, classically in healthcare workers or children with oral HSV. Eczema herpeticum is disseminated HSV superinfection of atopic dermatitis and can be life-threatening.

High-yield severe manifestations include HSV-1 encephalitis, which targets the temporal lobes and may cause fever, altered mental status, seizures, focal neurologic deficits, and hemorrhagic necrosis. CSF typically shows lymphocytic pleocytosis and elevated protein; red blood cells may be present. CSF HSV PCR is the diagnostic test of choice, with approximately 96% sensitivity and 99% specificity. Neonatal HSV is usually acquired intrapartum, especially with maternal primary genital infection, and may present as skin-eye-mouth disease, encephalitis, or disseminated hepatitis/pneumonitis.

Histologically, HSV produces multinucleated giant cells, nuclear molding, chromatin margination, and eosinophilic intranuclear Cowdry type A inclusions. A Tzanck smear can show multinucleated giant cells but cannot distinguish HSV from VZV; PCR from lesion swab is preferred.

Antiviral pharmacology

Acyclovir, valacyclovir, and famciclovir are guanosine analogs activated by viral thymidine kinase, then further phosphorylated by host kinases. They inhibit viral DNA polymerase and cause chain termination. Resistance usually results from thymidine kinase deficiency; foscarnet, a pyrophosphate analog that directly inhibits viral DNA polymerase, is used for resistant disease.

Drug	Key pharmacology	Common Step 1 dose examples
Acyclovir	Oral bioavailability 10–20%; half-life about 2.5–3 hours; renal elimination; can cause crystalline nephropathy	Severe HSV/encephalitis: IV 10 mg/kg every 8 hours
Valacyclovir	Prodrug of acyclovir; oral bioavailability about 54%	First-episode genital HSV: 1 g orally twice daily for 7–10 days
Famciclovir	Prodrug of penciclovir; longer intracellular half-life	Alternative oral agent for recurrent HSV

Varicella-Zoster Virus: HHV-3

Varicella-zoster virus is also an enveloped, double-stranded DNA alpha-herpesvirus. Primary infection causes varicella (“chickenpox”); reactivation causes herpes zoster (“shingles”). Transmission occurs via respiratory droplets or direct contact with vesicle fluid. The incubation period is typically 10–21 days, and patients are contagious from about 1–2 days before rash until all lesions crust.

Primary varicella begins with fever and malaise, followed by a pruritic vesicular rash. Lesions classically appear in successive crops, so macules, papules, vesicles, pustules, and crusts coexist. Distribution is usually centripetal, involving trunk and face more than distal extremities. Complications include bacterial superinfection, pneumonia, hepatitis, cerebellar ataxia, and encephalitis. Reye syndrome is associated with aspirin use in children with varicella or influenza.

After primary infection, VZV becomes latent in dorsal root or cranial nerve ganglia. Reactivation produces unilateral painful grouped vesicles in a dermatomal distribution that usually does not cross the midline. Pain often precedes the rash. Important complications include postherpetic neuralgia, especially in older adults; herpes zoster ophthalmicus involving V1, with Hutchinson sign indicating nasal tip lesions from nasociliary branch involvement; and Ramsay Hunt syndrome, due to geniculate ganglion involvement, causing ipsilateral facial paralysis, ear pain, and vesicles in the ear canal.

Diagnosis is usually clinical, but PCR of lesion fluid is most sensitive. Like HSV, VZV shows multinucleated giant cells and Cowdry type A inclusions. Treatment for uncomplicated zoster is most effective when started within 72 hours of rash onset; a common regimen is valacyclovir 1 g orally three times daily for 7 days. Severe disseminated VZV or disease in immunocompromised patients is treated with IV acyclovir.

Prevention is highly testable. The live attenuated varicella vaccine is given in 2 doses at 12–15 months and 4–6 years; live vaccines are contraindicated in pregnancy and severe immunosuppression. The recombinant zoster vaccine, Shingrix, contains VZV glycoprotein E with AS01B adjuvant and is recommended by ACIP for adults ≥50 years and immunocompromised adults ≥19 years, given as 2 doses separated by 2–6 months. Efficacy against herpes zoster is greater than 90% in immunocompetent older adults.

Warts and Molluscum Contagiosum

Warts

Warts are benign epidermal proliferations caused by human papillomavirus (HPV), a nonenveloped, circular double-stranded DNA virus that infects basal keratinocytes through microabrasions. HPV replicates in differentiating squamous epithelium and produces epidermal hyperplasia, hyperkeratosis, and papillomatosis. On histology, HPV infection classically produces koilocytes: squamous cells with perinuclear clearing and irregular, hyperchromatic nuclei.

HPV is highly tissue-tropic. Cutaneous warts are usually due to low-risk HPV types, whereas anogenital disease includes both low-risk and oncogenic types. High-risk HPV types encode E6 and E7 oncoproteins: E6 promotes degradation of p53, impairing apoptosis and DNA damage response; E7 binds Rb, releasing E2F transcription factors and driving inappropriate S-phase entry. This mechanism is most important for cervical, anal, penile, vulvar, vaginal, and oropharyngeal cancers, not ordinary cutaneous warts.

Clinical type	Typical HPV types	Appearance and location	High-yield association
Verruca vulgaris common wart	HPV 2, 4	Rough, hyperkeratotic papules on hands, fingers, periungual skin	Disrupts dermatoglyphics; thrombosed capillaries appear as black dots
Verruca plantaris plantar wart	HPV 1, 2, 4	Endophytic painful papule on sole, often at pressure points	Pain with lateral compression; may mimic callus
Verruca plana flat wart	HPV 3, 10	Flat-topped, smooth papules on face, dorsal hands, shins	May spread linearly by scratching, demonstrating the Koebner phenomenon
Condyloma acuminatum anogenital wart	HPV 6, 11	Soft, flesh-colored, cauliflower-like papules in anogenital mucosa	Low malignant potential, but indicates sexual HPV exposure
High-risk anogenital HPV	HPV 16, 18, 31, 33	Often subclinical or dysplastic lesions rather than exophytic warts	HPV 16 is the most common oncogenic type; HPV 18 is associated with adenocarcinoma

Diagnosis is usually clinical. Important differentials include corns and calluses, seborrheic keratosis, squamous cell carcinoma, and molluscum contagiosum. A callus preserves skin lines and lacks thrombosed capillary dots, whereas a wart interrupts skin lines. In immunocompromised patients, warts may be numerous, refractory, or atypical because cell-mediated immunity is central to HPV clearance.

Therapy is often destructive or immunomodulatory; many warts regress spontaneously. Approximately two-thirds of cutaneous warts resolve within 2 years in immunocompetent children. Common Step 1-relevant treatments include topical salicylic acid, cryotherapy, imiquimod, and physical destruction.

Therapy	Mechanism	Typical use or dose	Key adverse effects
Salicylic acid	Keratolytic; disrupts intercellular cohesion in stratum corneum	Usually 17% liquid for common warts; 40% plaster for plantar warts, applied daily after paring/soaking	Local irritation, maceration; avoid normal surrounding skin
Liquid nitrogen cryotherapy	Freeze-thaw injury causing keratinocyte necrosis and local inflammation	Often every 2-3 weeks; typical freeze time 10-30 seconds depending on lesion size	Pain, blistering, hypopigmentation, scarring
Imiquimod	TLR7 agonist increasing interferon-α and Th1 cytokines	For external genital/perianal warts: 5% cream 3 nights/week up to 16 weeks	Erythema, erosion, flu-like symptoms
Podofilox	Antimitotic agent causing wart necrosis	0.5% solution/gel for external genital warts; applied twice daily for 3 days, then 4 days off, up to 4 cycles	Local pain, ulceration; contraindicated in pregnancy

Prevention is high-yield. HPV vaccines are recombinant virus-like particle vaccines made from the L1 capsid protein; they contain no viral DNA and cannot cause infection. The 9-valent vaccine covers HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58. Routine vaccination is recommended at age 11-12 years, may begin at age 9, and uses a 2-dose series if started before age 15 or a 3-dose series if started at age 15 or later or in immunocompromised patients.

Molluscum Contagiosum

Molluscum contagiosum is caused by molluscum contagiosum virus, a large enveloped double-stranded DNA poxvirus. Unlike most DNA viruses, poxviruses replicate entirely in the cytoplasm because they carry their own DNA-dependent RNA polymerase. Transmission occurs by direct skin-to-skin contact, fomites, autoinoculation, or sexual contact in adults.

Lesions are classically small, firm, dome-shaped, pearly papules with central umbilication. They are often found on the face, trunk, extremities, or intertriginous areas in children; in adults, genital or lower abdominal lesions suggest sexual transmission. Lesions are usually 2-5 mm, but can become larger and more numerous in patients with impaired cell-mediated immunity, especially advanced HIV infection or iatrogenic immunosuppression.

Histology shows cup-shaped epidermal hyperplasia with large eosinophilic intracytoplasmic inclusion bodies called Henderson-Patterson bodies, representing aggregates of viral particles. These inclusions expand keratinocytes and displace the nucleus peripherally. This contrasts with HPV warts, which show koilocytosis rather than poxvirus inclusions.

Feature	Warts	Molluscum contagiosum
Virus family	HPV; nonenveloped circular dsDNA virus	Poxvirus; enveloped linear dsDNA virus
Replication site	Nucleus	Cytoplasm
Classic lesion	Hyperkeratotic or papillomatous papule	Pearly umbilicated papule
Histology	Koilocytes	Henderson-Patterson bodies
Immunity controlling disease	Cell-mediated immunity	Cell-mediated immunity

Molluscum contagiosum is benign and frequently self-limited; in immunocompetent children, spontaneous resolution commonly occurs within 6-18 months, though lesions may persist longer. Treatment is considered for symptoms, autoinoculation, cosmetic concerns, eczema around lesions, or extensive disease. Options include curettage, cryotherapy, topical cantharidin, or observation. Cantharidin is a vesicant that causes intraepidermal blistering through desmosomal disruption; it is applied in-office and then washed off after a specified exposure time to limit excessive blistering. The most important exam distinction is that molluscum is a poxvirus with umbilicated papules and cytoplasmic inclusions, whereas warts are HPV-driven epidermal proliferations with nuclear viral replication and koilocytosis.

Candida Infections

Organism and Basic Pathogenesis

Candida species are opportunistic, commensal fungi that colonize the oral cavity, gastrointestinal tract, vagina, and moist skin. The most important species for USMLE Step 1 is Candida albicans, a polymorphic fungus capable of existing as budding yeast, pseudohyphae, and true hyphae. This morphologic switching is a major virulence factor: yeast forms aid dissemination, whereas hyphal forms promote tissue invasion.

C. albicans virulence depends on adhesins, biofilm formation, secreted aspartyl proteases, phospholipases, and the yeast-to-hypha transition. On skin, Candida proliferates in warm, moist, macerated intertriginous areas, where disruption of the stratum corneum permits superficial invasion. Host defense against mucocutaneous Candida relies heavily on Th17-mediated immunity: IL-17 and IL-22 stimulate epithelial antimicrobial peptides and recruit neutrophils. Thus, chronic mucocutaneous candidiasis is classically associated with impaired T-cell/Th17 pathways, while invasive candidiasis is more strongly linked to neutropenia and indwelling catheters.

Predisposing Conditions

• Moisture and occlusion: obesity, skin folds, diapers, tight clothing, sweating.
• Antibiotic use: suppresses competing bacterial flora, allowing Candida overgrowth.
• Diabetes mellitus: hyperglycemia enhances fungal growth and impairs neutrophil function.
• Pregnancy and estrogen exposure: increased vaginal glycogen supports Candida growth.
• Immunodeficiency: HIV/AIDS, corticosteroids, chemotherapy, transplant immunosuppression.
• Primary immune defects: chronic mucocutaneous candidiasis due to impaired cell-mediated immunity, including AIRE mutation in autoimmune polyendocrine syndrome type 1 and gain-of-function STAT1 mutations affecting IL-17 responses.

Major Mucocutaneous Syndromes

Syndrome	Classic Findings	High-Yield Associations
Oral thrush	White, curd-like plaques on buccal mucosa or tongue that scrape off, leaving erythematous or bleeding mucosa	Infants, inhaled corticosteroids, antibiotics, HIV; oropharyngeal candidiasis often occurs with CD4 counts <200–300 cells/mm3
Esophageal candidiasis	Odynophagia, dysphagia, retrosternal pain; endoscopy shows white plaques	AIDS-defining illness; commonly treated systemically rather than topically
Candidal intertrigo	Beefy red erythematous plaques in folds with satellite papules or pustules	Inframammary, axillary, abdominal, groin folds; involves moist opposed surfaces
Diaper candidiasis	Erythematous rash involving skin folds with satellite lesions	Helps distinguish from irritant diaper dermatitis, which often spares folds
Vulvovaginal candidiasis	Pruritus, vulvar erythema, dysuria, thick “cottage cheese” discharge; vaginal pH usually normal, 4.0–4.5	Diabetes, pregnancy, antibiotics; recurrent disease is commonly defined by CDC as ≥3 symptomatic episodes in <1 year
Paronychia/onychomycosis	Painful erythematous nail fold swelling; chronic exposure to water	Dishwashers, healthcare workers; Candida nail disease differs from dermatophyte tinea unguium

Diagnosis

Diagnosis is often clinical but can be confirmed by microscopy. A scraping or swab treated with 10–20% potassium hydroxide (KOH) dissolves keratin and epithelial debris, revealing budding yeast with pseudohyphae. This finding is high yield and distinguishes Candida from dermatophytes, which show septate branching hyphae without budding yeast. C. albicans forms germ tubes when incubated in serum at 37°C for approximately 2 hours. Fungal stains such as PAS or Gomori methenamine silver can highlight organisms in tissue. Cultures may grow on Sabouraud agar but are not always required for typical superficial disease.

Pharmacology and Treatment Principles

Step 1 emphasizes drug mechanisms and toxicities. Superficial Candida is commonly treated with topical agents; systemic therapy is used for esophageal disease, severe mucosal disease, or refractory/recurrent infection.

Drug/Class	Mechanism	Common Regimens and Key Facts
Topical azoles clotrimazole, miconazole, ketoconazole	Inhibit fungal 14-α-demethylase, a CYP450 enzyme required for ergosterol synthesis	Clotrimazole 1% or miconazole 2% applied twice daily for intertrigo; vaginal azole courses often last 1–7 days depending on formulation
Fluconazole	Systemic triazole; inhibits ergosterol synthesis	Uncomplicated vulvovaginal candidiasis: 150 mg orally once. Oropharyngeal candidiasis: often 100–200 mg daily for 7–14 days. Half-life approximately 30 hours; renal elimination; adverse effects include hepatotoxicity, QT prolongation, CYP interactions, and teratogenic risk with high-dose/prolonged exposure
Nystatin	Polyene that binds ergosterol and forms membrane pores	Not absorbed orally, so useful for oral/GI mucosal Candida; topical powder or cream often 100,000 units/g applied 2–4 times daily
Echinocandins caspofungin, micafungin	Inhibit β-1,3-D-glucan synthase, weakening fungal cell wall	Mainly for invasive candidiasis or azole-resistant disease, not routine superficial skin infection

Key Differentiation from Tinea

Candida typically produces beefy red, moist plaques with satellite pustules and frequently involves skin folds, mucosa, and the scrotum. Dermatophyte tinea infections more often produce annular, scaly plaques with central clearing and usually spare mucosal surfaces because dermatophytes require keratinized tissue.

Tinea Infections

Tinea refers to superficial fungal infection caused by dermatophytes, filamentous molds that digest keratin in the stratum corneum, hair, and nails. Dermatophytes do not invade viable mucosa or deep tissue in immunocompetent hosts because they require keratinized substrate. The major genera are Trichophyton, Microsporum, and Epidermophyton. High-yield species include Trichophyton rubrum for tinea pedis, corporis, cruris, and onychomycosis; Trichophyton tonsurans for tinea capitis in the United States; and Microsporum canis from cats and dogs.

Pathogenesis and Classification

Dermatophytes produce keratinases and other proteases that allow adherence to and digestion of keratin. The host inflammatory response creates the classic annular plaque with central clearing: active fungal growth occurs at the advancing erythematous, scaly border, while the center partially resolves. Transmission occurs by direct contact with infected humans, animals, soil, or fomites. Occlusion, sweating, maceration, minor trauma, diabetes mellitus, and immunosuppression increase risk.

Clinical Type	Site	Classic Findings	High-Yield Notes
Tinea corporis	Trunk, extremities	Annular, erythematous, scaly plaque with central clearing	“Ringworm”; often confused with eczema or psoriasis
Tinea cruris	Groin, upper medial thigh	Pruritic erythematous plaques with advancing border	Usually spares scrotum; helps distinguish from candidal intertrigo
Tinea pedis	Feet	Interdigital scaling/maceration, moccasin distribution, or vesicles	Common portal for bacterial cellulitis
Tinea capitis	Scalp hair shafts	Scaling, alopecia, “black dots,” lymphadenopathy	Requires oral therapy; topical agents do not penetrate hair shafts adequately
Kerion	Inflammatory tinea capitis	Boggy, tender inflammatory plaque with pustules	Can scar and cause permanent alopecia
Tinea unguium	Nails	Thickened, yellow, brittle nails with subungual debris	Also called dermatophyte onychomycosis

Diagnosis

Diagnosis is often clinical but should be confirmed when the presentation is atypical, recurrent, extensive, or involves hair/nails. The key bedside test is a potassium hydroxide preparation. Skin scale, hair, or nail debris is treated with 10–20% KOH, which dissolves keratin and reveals branching septate hyphae on light microscopy. Dermatophytes form true hyphae, unlike Candida, which classically shows budding yeast with pseudohyphae.

Fungal culture is more specific but slower, often requiring 1–4 weeks. Wood lamp examination is organism-dependent: some Microsporum species fluoresce blue-green, whereas T. tonsurans, the common U.S. cause of tinea capitis, usually does not fluoresce. Nail disease may be confirmed by KOH, fungal culture, or periodic acid–Schiff staining of nail clippings.

Pharmacology and Treatment Principles

Therapy depends on anatomic site. Topical therapy is appropriate for most localized tinea corporis, cruris, and pedis. Oral therapy is required for tinea capitis, extensive disease, immunocompromised patients, and most dermatophyte onychomycosis.

Drug Class	Mechanism	Common Regimens	Important Adverse Effects / Interactions
Allylamines: terbinafine, naftifine	Inhibit squalene epoxidase → decreased ergosterol synthesis and toxic squalene accumulation	Topical terbinafine 1% once or twice daily for 1–2 weeks; oral terbinafine 250 mg daily for 6 weeks for fingernails or 12 weeks for toenails	Hepatotoxicity, taste disturbance, headache; check liver disease history before oral therapy
Azoles: clotrimazole, miconazole, ketoconazole, itraconazole, fluconazole	Inhibit fungal 14-α-demethylase, a CYP450 enzyme → impaired ergosterol synthesis	Topical clotrimazole 1% twice daily for 2–4 weeks; itraconazole 200 mg daily for 12 weeks for toenail onychomycosis	CYP450 inhibition, hepatotoxicity, QT prolongation; itraconazole has negative inotropic effects
Griseofulvin	Binds fungal microtubules → inhibits mitosis; deposits in keratin precursor cells	Tinea capitis: microsize 20–25 mg/kg/day for 6–8 weeks	Headache, GI upset, photosensitivity; induces CYP450; teratogenic, avoid pregnancy

For tinea capitis, oral griseofulvin or terbinafine is standard. Terbinafine is often more effective for Trichophyton, whereas griseofulvin remains useful for Microsporum. Adjunctive selenium sulfide 1–2.5% or ketoconazole shampoo 2–3 times weekly can reduce spore shedding but is not sufficient alone. For tinea pedis, keeping interdigital spaces dry and treating shoes/socks reduces recurrence.

Key Differentials and Pitfalls

A major Step 1 pitfall is tinea incognito, a dermatophyte infection altered by topical corticosteroids. Steroids suppress inflammation, making lesions less scaly and less annular while allowing fungal proliferation. Suspect it when a “dermatitis” worsens with corticosteroids.

• Candidal intertrigo: beefy red plaques with satellite pustules; often involves scrotum and moist folds.
• Psoriasis: sharply demarcated plaques with silvery scale; KOH negative.
• Nummular eczema: coin-shaped pruritic plaques without central clearing; KOH negative.
• Pityriasis rosea: herald patch followed by “Christmas tree” distribution; not a dermatophyte infection.

High-yield summary: tinea infections are dermatophyte infections of keratinized tissue diagnosed by KOH showing branching septate hyphae; topical allylamines or azoles treat localized skin disease, while scalp and nail disease generally require systemic antifungals.

Scabies

Scabies is an intensely pruritic ectoparasitic infestation caused by the mite Sarcoptes scabiei var. hominis. It is transmitted primarily by prolonged skin-to-skin contact; brief casual contact is usually insufficient. For USMLE Step 1, the key concept is that symptoms are driven less by mechanical mite damage and more by a type IV delayed hypersensitivity reaction to mite proteins, eggs, and fecal pellets within the stratum corneum.

Microbiology and Pathogenesis

The adult female mite burrows into the stratum corneum, where she lays eggs and deposits fecal material. Eggs hatch in approximately 3–4 days, larvae mature through nymph stages, and the life cycle is completed in about 10–14 days. Adult mites survive on humans for about 1–2 months, but off the host usually survive only 24–36 hours under typical room conditions.

The average patient with classic scabies has a small mite burden, often only 10–15 mites, yet can have severe pruritus because the immune system reacts vigorously to mite antigens. Initial infestation has an incubation period of approximately 2–6 weeks before itching develops; reinfestation produces symptoms much faster, often within 1–4 days, due to immunologic memory.

Clinical Features

The hallmark is intense pruritus that is worse at night. Lesions are often excoriated, so primary findings may be subtle. Classic morphology includes small erythematous papules, vesicles, and linear or serpiginous burrows. Burrows represent tunnels made by the female mite in the stratum corneum.

Feature	High-yield details
Distribution	Finger webs, flexor wrists, elbows, anterior axillary folds, periumbilical skin, waistline, buttocks, genitalia; in infants, scalp, face, palms, and soles may be involved
Symptoms	Severe nocturnal pruritus; multiple household or close contacts often itch
Pathology	Eosinophil-rich hypersensitivity reaction; burrows confined to stratum corneum
Complications	Excoriations may become secondarily infected with Staphylococcus aureus or Streptococcus pyogenes; impetigo and poststreptococcal glomerulonephritis are possible

Classic Versus Crusted Scabies

Crusted scabies, also called Norwegian scabies, is a severe hyperinfestation classically associated with impaired cell-mediated immunity, including advanced HIV/AIDS, hematologic malignancy, transplantation, chronic glucocorticoid therapy, neurologic disability, or institutionalization. Unlike classic scabies, mite burden may reach thousands to millions, making it highly contagious. Pruritus may be mild or absent because of impaired immune response.

Type	Mite burden	Typical host	Clinical appearance
Classic scabies	Usually 10–15 mites	Immunocompetent	Pruritic papules and burrows, especially finger webs and wrists
Crusted scabies	Thousands to millions	Immunocompromised, elderly, institutionalized, neurologically impaired	Hyperkeratotic crusted plaques, thick scale, fissures; often widespread

Diagnosis

Diagnosis is often clinical when nocturnal pruritus, typical distribution, and affected contacts are present. Confirmation can be obtained by identifying mites, eggs, or scybala fecal pellets on skin scraping examined under light microscopy. Mineral oil is commonly used to collect material from burrows. Dermoscopy may show the “delta-wing jet” or “hang glider” sign, representing the mite’s anterior body at the end of a burrow.

A negative scraping does not exclude scabies because classic infestation has low mite burden. Step 1 questions often emphasize pattern recognition rather than test performance: intensely pruritic papules in finger webs and wrists with nocturnal itching and symptomatic contacts is scabies until proven otherwise.

Pharmacology and Treatment Principles

Although detailed treatment strategy is more clinical than Step 1-focused, the drug mechanisms are high-yield. Permethrin 5% cream is first-line for classic scabies. It is a synthetic pyrethroid that disrupts arthropod voltage-gated sodium channels, causing paralysis and death of mites. It is applied from neck down, often including scalp and face in infants or elderly patients, left on for 8–14 hours, then washed off; repeat treatment is commonly performed in 7 days to kill newly hatched mites.

Ivermectin is an oral antiparasitic that binds glutamate-gated chloride channels in invertebrate nerve and muscle cells, increasing chloride influx, hyperpolarizing cells, and causing paralysis. Typical dosing for scabies is 200 micrograms/kg orally, repeated in 7–14 days. It has a plasma half-life of approximately 18 hours. Ivermectin is especially useful for outbreaks, adherence barriers, and crusted scabies, but is generally avoided in pregnancy and in children weighing less than 15 kg in many guidelines.

Drug	Mechanism	Typical regimen	Key cautions
Permethrin 5% cream	Prolongs arthropod sodium channel opening → paralysis	Apply 8–14 hours; repeat in 7 days	Generally safe; local irritation possible
Ivermectin	Activates glutamate-gated chloride channels → hyperpolarization	200 micrograms/kg orally; repeat in 7–14 days	Avoid or use caution in pregnancy and children <15 kg
Lindane	Interferes with GABA-mediated neurotransmission in parasites	Older alternative, rarely used	Neurotoxicity and seizures; avoid in infants, pregnancy, extensive dermatitis

Public Health and Exam Pearls

• Treat close contacts simultaneously, including household members and sexual contacts, even if asymptomatic, because incubation can be weeks.
• Wash clothing, towels, and bedding used in the prior 3 days in hot water and dry on high heat, or seal items in a plastic bag for at least 72 hours.
• Pruritus may persist for 2–4 weeks after successful therapy due to residual hypersensitivity; this does not necessarily indicate treatment failure.
• Crusted scabies requires aggressive therapy, often combined topical permethrin plus repeated oral ivermectin, and strict infection-control measures.
• Classic differential diagnoses include atopic dermatitis, allergic contact dermatitis, bedbug bites, pediculosis, dermatitis herpetiformis, and papular urticaria; the combination of nocturnal itch, burrows, finger-web involvement, and affected contacts is most characteristic.