Skin Infections and Infestations Pathology

Bacterial Skin Infections

• Colonization and virulence factor expression: Pathogenic bacteria (predominantly Staphylococcus aureus and Streptococcus pyogenes) express adhesins (fibronectin-binding proteins, collagen-adhesin) enabling epithelial attachment and biofilm formation; virulence factors include exotoxins (alpha-toxin, Panton-Valentine leukocidin), superantigens, and hyaluronidase that facilitate tissue invasion and immune evasion
• Neutrophilic inflammation and tissue destruction: Host neutrophils and macrophages respond to bacterial PAMPs and chemotactic factors, releasing proteases (elastase, collagenase) and reactive oxygen species that cause acute suppurative inflammation and tissue necrosis; in streptococcal infections, hyaluronic acid mimicry of host extracellular matrix prevents opsonization
• Depth of involvement and barrier disruption: Disruption of the stratum corneum through abrasions, moisture, or occlusion creates portals of entry; follicular obstruction with sebum and keratin enables pilosebaceous unit infection; superficial infections remain localized while deeper penetration activates dermal and subcutaneous responses

Viral Skin Infections

• Direct cytopathic effect and apoptosis: DNA and RNA viruses replicate within keratinocytes, inducing ballooning degeneration (cytoplasmic swelling with loss of cell-cell adhesion), acantholysis (loss of desmosomes), and apoptosis via viral protease and endonuclease activation; herpesviruses establish latency in sensory ganglia with periodic reactivation
• Immune-mediated inflammation: Interferon-alpha and -beta responses, followed by CD8+ T-cell infiltration, drive both viral clearance and tissue inflammation; in severe cases (disseminated HSV, VZV), viral dissemination exploits deficient cell-mediated immunity
• Viral particle transport and neurotropism: Herpes viruses utilize retrograde axonal transport along sensory nerves, explaining dermatomal distribution in varicella-zoster and localized recurrence in herpes simplex; some viruses (HPV) persistently infect basal keratinocytes without cytolysis

Fungal Skin Infections

• Keratinolytic enzyme production and biofilm formation: Dermatophytes (phyla Ascomycota) secrete keratinolytic proteases (Trichophyton, Epidermophyton, Microsporum species), breaking down alpha-keratin in stratum corneum; candida species produce aspartyl proteinases enabling epithelial invasion in moist environments with reduced local immunity
• Host inflammatory response to fungal antigens: Fungal cell wall components (beta-glucans, mannans) activate pattern recognition receptors (TLR2, Dectin-1), triggering Th1 and Th17 responses; in dermatophyte infections, delayed-type hypersensitivity (DTH) reactions can paradoxically worsen inflammation (kerion formation in tinea capitis)
• Barrier dysfunction and moisture exploitation: Fungi preferentially colonize areas of increased moisture and occlusion (interdigital spaces, inframammary folds, groin); reduced sebum antimicrobial peptides (including free fatty acids) in some individuals increase susceptibility

Parasitic Infestations

• Direct mechanical irritation and allergic sensitization: Ectoparasites (scabies mites, lice) burrow into epidermis or attach to hair, creating mechanical trauma and releasing antigens; in scabies, the host develops cell-mediated hypersensitivity (DTH) to mite antigens after 3-6 weeks, explaining delayed symptom onset in primary infestation
• Toxin-mediated inflammation: Scabies mites secrete proteases and other factors causing chronic eczematous dermatitis; sarcoptic mange mites trigger intense pruritus through neurogenic inflammation
• Secondary bacterial infection pathway: Intense scratching disrupts barrier integrity, enabling secondary S. aureus and S. pyogenes superinfection, often with methicillin resistance

Bacterial Skin Infections

• Staphylococcus aureus (including methicillin-resistant MRSA) — most common cause of impetigo, folliculitis, abscesses, and surgical site infections; produces alpha-toxin, PVL, and enterotoxins
• Streptococcus pyogenes (Group A Streptococcus) — primary pathogen in cellulitis, erysipelas, and impetigo; produces hyaluronidase and M protein for immune evasion
• Pseudomonas aeruginosa — opportunistic pathogen in immunocompromised states, diabetics, and burn wounds; produces exotoxin A and biofilm-forming capacity
• Other gram-negative organisms (E. coli, Klebsiella, Proteus) in diabetics with foot ulcers and immunocompromised patients

Viral Skin Infections

• Herpesvirus family: HSV-1/2 (oral/genital herpes), VZV (varicella, zoster), CMV, EBV — enveloped DNA viruses establishing latency
• Papillomaviruses (HPV): >200 genotypes; low-risk types (6, 11) cause benign warts; high-risk types (16, 18) associated with malignant transformation
• Poxviruses: Molluscum contagiosum, monkeypox — large DNA viruses with characteristic umbilicated lesions
• Enteroviruses: Coxsackieviruses, echoviruses causing hand-foot-mouth disease and exanthems

Fungal Skin Infections

• Dermatophytes: Trichophyton tonsurans (most common in North America), T. rubrum, Microsporum canis, Epidermophyton floccosum
• Candida species: Candida albicans (most common); predisposed by antibiotics, diabetes, immunosuppression, dentures
• Malassezia species: M. globosa, M. furfur causing tinea (pityriasis) versicolor and seborrheic dermatitis
• Environmental molds: Aspergillus, Cryptococcus, Coccidioides in immunocompromised and geographic exposures

Parasitic Infestations

• Scabies: Sarcoptes scabiei hominis — obligate human parasite transmitted by direct skin contact; 8-legged mite
• Pediculosis: Pediculus humanus capitis (head lice), P. humanus corporis (body lice), Phthirus pubis (pubic lice) — insecta requiring blood meals
• Other parasites: Cutaneous larva migrans (Ancylostoma, Necator), swimmer's itch (Schistosoma), creeping eruption
• Arthropod infestations: Chiggers (Trombiculidae), mites (Demodex), bedbugs (Cimex lectularius)

Risk Factors (Universal)

• Compromised skin barrier (abrasions, eczema, psoriasis, atopic dermatitis)
• Immunosuppression (HIV/AIDS, chemotherapy, organ transplant, biologics)
• Poor hygiene and overcrowded living conditions
• Diabetes mellitus (impaired neutrophil function and hyperglycemia)
• Extremes of age (neonates, elderly with thin epidermis)
• Moisture and occlusion (maceration in intertriginous areas)
• Previous antibiotic use (disrupts commensal flora)

Bacterial Infections

• Impetigo (streptococcal and staphylococcal):
• Non-bullous (70%) — begins as erythematous papules progressing to honey-crusted erosions on exposed areas (face, extremities); classic presentation in children aged 2-5 years
• Bullous (30%) — flaccid bullae with rapid rupture; S. aureus produces exfoliative toxins (ETA, ETB) causing subcorneal acantholysis
• Regional lymphadenopathy common; generally non-systemic except in immunocompromised

• Cellulitis:
• Acute onset (24-72 hours) of ill-defined erythema, edema, warmth, and tenderness; typically unilateral lower extremity but can occur anywhere
• Streaking lymphangitis along draining vessels with regional lymphadenopathy pathognomonic for streptococcal infection
• Systemic signs: fever, chills, malaise; potential progression to bacteremia and sepsis

• Erysipelas:
• Superficial cellulitis restricted to dermis and superficial lymphatics; classically streptococcal (S. pyogenes)
• Sharply demarcated, bright red plaques with raised borders (raised above surrounding normal skin, unlike cellulitis)
• Facial butterfly distribution or lower extremity; rapid onset (12-24 hours)

• Folliculitis and Furuncles:
• Suppurative infection of hair follicles; furuncles are deeper abscesses with central pustule
• Pustule with surrounding erythema on hair-bearing areas; can coalesce into carbuncles (multiple connected furuncles with sinus tracts)
• Often preceded by minor trauma (shaving, plucking)

• Abscesses and Boils:
• Localized collections of pus with central necrosis; S. aureus (including MRSA) most common
• Fluctuant nodules with surrounding cellulitis; drainage may be spontaneous or require incision

Viral Infections

• Herpes Simplex Virus (HSV-1/2):
• Primary infection: painful vesicles on erythematous base with prodrome (burning, tingling); grouped arrangement; severe in genital HSV or immunocompromised
• Recurrent infection (reactivation): similar but less severe, preceded by dermatomal paresthesias; heals within 7-10 days
• Herpetic whitlow: digital involvement with severe pain; risk for dissemination if immunocompromised
• Microscopy: multinucleated giant cells, molding of nuclei, Cowdry type A intranuclear inclusions (eosinophilic, surrounded by halo)

• Varicella-Zoster Virus (VZV):
• Varicella (chickenpox): vesicles in different stages of evolution (hallmark: mixture of macules, papules, vesicles, crusts) on centripetal distribution (face, trunk > extremities); high fever and systemic symptoms
• Herpes zoster (shingles): dermatomal distribution (unilateral, does not cross midline) of painful vesicles; prodromal pain may precede rash by days; postherpetic neuralgia in older adults
• Microscopy: identical to HSV with multinucleated giant cells and nuclear inclusions

• Human Papillomavirus (HPV):
• Common warts: hyperkeratotic, verrucous papules on fingers/hands; may show characteristic punctate black dots (thrombosed capillaries)
• Plantar warts: pressure-related lesions on feet; can be painful; may show similar "seed" pattern
• Genital warts: flesh-colored, warty growths on genitalia/perianal region; often multiple
• Microscopy: koilocytes (HPV-infected cells with perinuclear clearing and wrinkled nuclei), hyperkeratosis, acanthosis

• Molluscum Contagiosum:
• Umbilicated papules (central dimple/depression) — pathognomonic; skin-colored to pinkish; 2-5 mm diameter
• Transmitted by direct contact, fomites; highly contagious in children
• Microscopy: intracytoplasmic molluscum bodies (large, oval, eosinophilic inclusions) within keratinocytes; minimal inflammation

Fungal Infections

• Tinea Pedis (Athlete's Foot):
• Interdigital involvement (most common): maceration, erythema, pruritus between toes; may progress to ulceration and secondary infection
• Vesicular form: blisters on plantar surface
• Moccasin distribution: dry, scaly hyperkeratosis over heel and plantar foot
• Often malodorous; warm, moist environment perpetuates infection

• Tinea Corporis (Ringworm):
• Annular plaques with central clearing — classic "ringworm" appearance; active border shows scale and inflammation
• Sharply demarcated, centrally healing lesions; proximal extremities and trunk most common
• Pruritus variable; may have satellite lesions from auto-inoculation

• Tinea Capitis:
• Circular patches of alopecia with gray-scale appearance; can be inflammatory (pustular) or non-inflammatory
• Kerion — severe inflammatory variant with pustular drainage and lymphadenopathy; often confused with bacterial infection
• Microsporum species may show blue-green fluorescence under Wood's lamp (not all species)

• Candidiasis:
• Erythematous, macerated patches in intertriginous areas (inframammary, inguinal, interdigital)
• Satellite pustules at borders (pathognomonic for candidiasis vs. dermatophytes)
• Erosions and maceration; often burning rather than pruritic
• Microscopy: pseudohyphae and yeast forms (smaller than dermatophyte hyphae)

• Tinea Versicolor (Pityriasis Versicolor):
• Hypo- or hyperpigmented macules/patches on chest, back, shoulders; "spaghetti and meatballs" appearance
• Scale easily wiped away; non-inflamed; caused by lipophilic Malassezia species
• Enhanced by warm, moist environments; more noticeable in tanned individuals

Parasitic Infestations

• Scabies:
• Intense pruritus (often worse at night and with heat); delayed onset in primary infestation (3-6 weeks)
• Burrows — pathognomonic linear or S-shaped tracks in stratum corneum, most common on interdigital webs, wrists, elbows, genitalia
• Inflammatory papules and nodules from secondary sensitization; excoriation with secondary infection common
• Nodular scabies variant: pruritic nodules on genitalia, axillae, buttocks (mite-rich lesions)
• Microscopy: female mite with ova and fecal pellets within burrow; can visualize under 10x magnification with immersion oil

• Pediculosis:
• Intense pruritus with small erythematous papules and excoriations at bite sites
• Head lice: Pediculus humanus capitis — nits (eggs) visible on hair shafts close to scalp; occipital and postauricular distribution
• Body lice: P. humanus corporis — les

Bacterial infection — clinical first, imaging when purulence is uncertain

• Cellulitis/erysipelas: a clinical diagnosis. The 2014 IDSA skin and soft tissue infection (SSTI) guideline advises against routine blood cultures, needle aspiration, or biopsy in uncomplicated cellulitis; obtain blood cultures when the patient is immunocompromised, has systemic toxicity, or has an immersion/animal-bite exposure.
• Point-of-care ultrasound: distinguishes drainable abscess (anechoic/hypoechoic collection with posterior acoustic enhancement) from phlegmon — the single most useful bedside test when fluctuance is equivocal.
• Abscess: culture the purulent drainage obtained at incision and drainage to identify MRSA and guide therapy.
• Necrotizing infection: surgical exploration is the gold standard (grey, non-bleeding fascia that separates with blunt finger dissection). The LRINEC score (CRP, WBC, hemoglobin, sodium, creatinine, glucose) may support suspicion but a low score never excludes it; imaging must not delay the operating room.
• Pseudocellulitis: bilateral lower-leg "cellulitis" is almost always stasis dermatitis; the ALT-70 score (asymmetry, leukocytosis, tachycardia, age ≥70) has been proposed to identify true cellulitis.

Viral

• HSV/VZV: PCR of vesicle base scrapings is the confirmatory test of choice (highest sensitivity, distinguishes HSV-1, HSV-2, VZV). Tzanck smear showing multinucleated giant cells is fast but cannot separate the herpesviruses. Direct fluorescent antibody is an alternative where PCR is unavailable.
• Verruca and molluscum: diagnosed clinically; paring a wart reveals thrombosed capillaries and loss of skin lines, which distinguishes it from callus.

Fungal and parasitic

• KOH preparation of scale is the initial test — septate branching hyphae in dermatophytosis, pseudohyphae with budding yeast in candidiasis, "spaghetti and meatballs" in pityriasis versicolor. Fungal culture on Sabouraud agar or PAS-stained biopsy confirms when KOH is negative but suspicion persists; nail and scalp disease should be confirmed before committing to systemic therapy.
• Scabies: dermoscopy (delta-wing jet sign) then mineral-oil skin scraping showing mites, eggs, or scybala confirms; a negative scraping does not exclude infestation.

Immediate priorities

• Necrotizing soft tissue infection is a surgical emergency: per IDSA, urgent debridement plus empiric broad-spectrum therapy — a beta-lactam/beta-lactamase inhibitor (piperacillin-tazobactam) plus vancomycin, with clindamycin added for ribosomal suppression of streptococcal exotoxin. Vancomycin is dosed to a 24-hour AUC targeting AUC/MIC 400–600 (2020 IDSA/ASHP consensus); trough-only targeting of 15–20 mcg/mL is obsolete.
• Abscess: incision and drainage is the definitive treatment. IDSA recommends adjunctive systemic antibiotics for surrounding cellulitis, systemic signs, immunosuppression, or failed drainage.

Bacterial, by syndrome

• Nonpurulent cellulitis/erysipelas: streptococci predominate, so a beta-lactam (cephalexin, or penicillin for classic erysipelas) is first line; add MRSA coverage only for penetrating trauma, injection drug use, or systemic toxicity.
• Purulent/MRSA-suspected: TMP-SMX or doxycycline orally; clindamycin is an alternative but carries inducible resistance and C. difficile risk.
• Impetigo: topical mupirocin for limited disease; oral cephalexin or dicloxacillin when lesions are numerous or bullous.
• Penicillin allergy: cephalosporins are usually safe — true cross-reactivity is about 1–3% and driven by shared R1 side chains, not the beta-lactam ring; the historical 10% figure should not be quoted.

Viral

• Nucleoside analogues (acyclovir, valacyclovir): started ideally within 72 hours of zoster rash onset; suppressive dosing for frequent HSV recurrence per CDC guidance.
• Molluscum: self-limited; cantharidin, curettage, or cryotherapy if desired. Warts: salicylic acid and cryotherapy first line.

Fungal and parasitic

• Topical allylamine/azole (terbinafine, clotrimazole) for tinea corporis/pedis; oral therapy is mandatory for tinea capitis (griseofulvin or terbinafine) and onychomycosis because topicals do not penetrate hair shaft or nail plate.
• Permethrin 5% cream for scabies, repeated in one week, with simultaneous treatment of all household contacts and bedding decontamination; oral ivermectin for crusted scabies or outbreaks (avoid in children <15 kg).

Streptococcal sequelae

• Post-streptococcal glomerulonephritis: immune-complex deposition after nephritogenic S. pyogenes impetigo; signaled by cola-colored urine, hypertension, periorbital edema, low C3. Antibiotic treatment of the skin lesion does not prevent it.
• Acute rheumatic fever: follows pharyngeal, not cutaneous, streptococcal infection — a favorite distractor.

Toxin-mediated and invasive emergencies

• Staphylococcal scalded skin syndrome (emergency): hematogenous exfoliative toxin cleaves desmoglein-1, producing a positive Nikolsky sign with sparing of mucous membranes (contrast with toxic epidermal necrolysis, which involves mucosa).
• Toxic shock syndrome (emergency): superantigen-driven massive T-cell activation → fever, hypotension, diffuse macular erythroderma, later desquamation.
• Necrotizing fasciitis (emergency): pain out of proportion to findings, rapidly advancing dusky skin, crepitus, systemic toxicity — go to the operating room, not to imaging.
• Bacteremia, endocarditis, and osteomyelitis: hematogenous seeding from S. aureus SSTI.

Chronic and viral complications

• Lymphatic damage with recurrent cellulitis: each episode scars dermal lymphatics, creating a self-perpetuating cycle; treat interdigital tinea pedis, the usual portal of entry.
• Eczema herpeticum (emergency): HSV disseminating through barrier-defective atopic skin — monomorphic punched-out erosions with fever; requires systemic acyclovir.
• Herpes zoster ophthalmicus (emergency): V1 involvement with Hutchinson sign (nasal tip vesicles) predicts ocular disease; urgent ophthalmology referral. Ramsay Hunt syndrome pairs facial palsy with ear canal vesicles.
• Postherpetic neuralgia: sensory ganglion damage; risk rises with age and is reduced by recombinant zoster vaccination (ACIP recommends it for adults ≥50).
• HPV-associated squamous cell carcinoma with high-risk types 16 and 18.
• Crusted (Norwegian) scabies: hyperinfestation in HIV/HTLV-1 or debility; enormously contagious.

Treatment-related

• TMP-SMX: hyperkalemia, creatinine rise, and severe cutaneous adverse reactions.
• Vancomycin: nephrotoxicity, minimized by AUC-guided dosing; infusion reaction from mast-cell degranulation.
• Terbinafine/griseofulvin: hepatotoxicity and CYP-mediated interactions (griseofulvin reduces oral contraceptive efficacy).
• Post-scabetic pruritus persisting weeks after cure — do not reflexively re-treat.

• Honey-colored crust on a child's face is nonbullous impetigo; the tested association is post-streptococcal glomerulonephritis, never rheumatic fever, and antibiotics do not prevent the nephritis.
• Erysipelas versus cellulitis: erysipelas is dermal/superficial lymphatic, sharply demarcated and raised, streptococcal, and rapid; cellulitis is deeper with indistinct borders. Bilateral lower-leg "cellulitis" in an afebrile patient is almost always stasis dermatitis — the classic distractor.
• Purulent equals drain: for a fluctuant abscess the single best next step is incision and drainage, not antibiotics alone (IDSA 2014). Nonpurulent cellulitis is treated with a streptococcal-directed beta-lactam such as cephalexin; MRSA coverage is not automatic.
• Pain out of proportion to exam, crepitus, or rapid dusky progression → necrotizing fasciitis → emergent surgical exploration, plus vancomycin (AUC/MIC 400–600), piperacillin-tazobactam, and clindamycin for toxin suppression. Do not order MRI first.
• Umbilicated papules = molluscum contagiosum (poxvirus, intracytoplasmic molluscum bodies); widespread facial molluscum in an adult should prompt HIV testing. Koilocytes = HPV.
• Tzanck smear multinucleated giant cells cannot distinguish HSV from VZV — PCR of the vesicle base is the confirmatory test. Vesicles at the nasal tip (Hutchinson sign) mean herpes zoster ophthalmicus and same-day ophthalmology.
• Tinea capitis and onychomycosis require oral antifungals; topical agents fail because they do not reach the hair shaft or nail bed. Steroid on tinea produces tinea incognito — a common wrong answer.
• Scabies: nocturnal pruritus with interdigital burrows; treat with topical permethrin plus all close contacts and bedding, repeat in one week. Itching that persists for weeks after successful treatment is post-scabetic hypersensitivity, not treatment failure.