Infectious Diseases Flashcards
Double-stranded DNA virus that infects skin and mucosal epithelial cells which is species-specific and require fully differentiated squamous epithelia for their life cycle
Human Papilloma Virus
HPV early proteins (E1-E7)
Responsible for DNA replication and kertinocyte immortalization
HPV late proteins (L1-L2)
Expressed in superficial epidermis and encode structural proteins required for virion formation
HPV Capsid
Contains DNA
Composed of L1 (major structural protein) and L2 (minor structural protein) – important for binding/entering epithelial cells
First to be expressed at strata basale and spinosum – control transcription of other genes + replication of viral DNA (using host cell machinery)
E1 and E2 genes
Disrupts cytokeratin network → koilocytosis
E4 protein
Allow viral replication above stratum basale → amplification
E5, E6, and E7 genes
Decrease host immune response; in high-risk mucosal subtypes are oncoproteins
E6 and E7 genes
E6 → ubiquitin-mediated p53 destruction →↓apoptosis/↑replication/↑mutations
E7 binds RB → loss of inhibition of E2F transcription factor → ↑expression of genes important for DNA replication
Genus that account for most known types
α - most of the mucosal and cutaneous HPV types
β - epidermodysplasia verruciformis (EV)-associated HPV types
Common warts
HPV-1, HPV-2, HPV-4, HPV-27, and HPV-57 (can cause 10 nail dystrophy)
Hyperkeratotic papules with pinpoint black dots (thrombosed capillaries), most commonly on fingers, dorsal hands/elbows/knees
Palmar/plantar warts
HPV-1, HPV-2, HPV-4, HPV-27, and HPV-57
Thick/deep endophytic papules with black dots on palms/soles
Flat/plane warts
HPV-3, HPV-10, HPV-28, and HPV-41
Light pink/brown, soft/smooth, slightly raised, occ. linear flat-topped papules on dorsal hands/face; more common in children; adult women ≫ adult men
Butchers warts
HPV-7 and HPV-2
Extensive lesions on hands in meat/fish-handlers
Epidermodysplasia verruciformis
Genetic disorder in which host has susceptibility to genus β HPV types (HPV-3, HPV-5, HPV-8, HPV-9, HPV-12, HPV-14, HPV-15, HPV-17, HPV-19, HPV-25, HPV-36, and HPV-38)
Generalized polymorphic papules (generally flat wart-like appearance (dorsal hands, neck, face, and extremities), but also scaly, pink macules or hypopigmented, guttate macules/patches, and seborrheic keratosis-like lesions on forehead/neck/trunk) with AD inheritance – mutations in TMC6 (EVER1) and TMC8 (EVER2); acquired form may be seen in HIV
HPV types 5 and 8 can → AKs and SCC (generally patients ≥30 years old in sun-exposed areas; >30% of pts will develop SCC)
Epidermodysplasia verruciformis
WHIM syndrome
AD 1° immunodeficiency caused by a CXCR4 mutation – Warts, Hypogammaglobinemia, Infections (bacterial), and neutropenia (2° to Myelokathexis)
WILD syndrome
Warts, Immunodeficiency, Lymphedema, and Dysplasia (anogenital)
Most common STD which occur on external genitals/perineum/perianal/groin/mons/vagina/urethra/anal canal; smooth, sessile, raised, skin-colored to brown lobulated papules
Most cases resolve spontaneously within 2 years
RFs: sexual intercourse at young age, # of sexual partners, and MSM
Circumcision →↓risk HPV transmission
May → cervical cancer
Condylomata acuminata (Genital warts) HPV-6, HPV-11, HPV-16, HPV-18, HPV-31, HPV-33, and HPV-45
HPV type of Condylomata acuminata with highest risk for cancer
HPV-16, HPV-18, HPV-31, HPV-33, and HPV-45
Multiple brown papules/smooth plaques on genitals/perineum/perianal that are high-grade squamous intraepithelial lesions (HSIL) or SCCIS; progression to invasive SCC is very rare; a/w high-risk HPV types
Bowenoid papulosis
Red smooth plaque on glabrous penis/vulva that is HSIL or SCCIS; increased risk of progression to invasive SCC; has high-risk HPV types
Erythroplasia of Queyrat
Part of a group of verrucous carcinomas (slow growing and locally destructive) that includes oral florid papillomatosis (HPV-6, HPV-11; RFs: smoking, radiation, and inflammation), epithelioma cuniculatum (HPV-2, HPV-11, and HPV-16), and papillomatis cutis carcinoides
HPV-6 and HPV-11
Cauliflower-like tumors that infiltrate deeply on external genitals and perianally
Buschke-Lowenstein tumor
Histology: papillomatous acanthotic epidermis with bulbous (“pushing”) downward-extending rete ridges; no cellular atypia/basement membrane penetration
Buschke-Lowenstein tumor
Histology: flat wart-like architecture + cells w/ perinuclear halos and blue-gray granular cytoplasm
Epidermodysplasia verruciformis
Multiple flat wart-like papules on gingival/buccal/labial mucosa in children (esp. South American); HPV-13 and HPV-32
Focal epithelial hyperplasia (Heck’s disease)
Papillomas of airways due to HPV-6 and HPV-11; #1 benign tumor of larynx; hoarseness + stridor + respiratory distress; childhood (2° to vertical transmission) and adulthood (2° to genital-to-oral contact) onsets; can → SCC, esp. in smokers
Recurrent respiratory papillomatosis
Characterized by an icosahedral capsid containing linear double-stranded DNA, surrounded by a glycoprotein-containing envelope; replicate in host nucleus
Human herpes viruses
HSV-1/HHV-1
Orolabial
1° HSV can be severe (gingivostomatitis in children; pharyngitis/mononucleosis-like in adults)
Mouth (esp. buccal mucosa and gingivae; favors anterior mouth unlike herpangina) and lips (recurrent lesions prefer vermilion border) affected
HSV-2/HHV-2
Genital
1° infection often asymptomatic, but can → painful/tender erosions on external genitalia, vagina, cervix, buttocks, and perineum (women) +/− lymphadenopathy/dysuria (women mainly)
Recurrent – mildly symptomatic with few vesicles lasting about 1 week; frequency of outbreaks usually decreases over time
Latent HSV infection
virus lies dormant in sensory (dorsal root) ganglia
Pathogenesis: Herpes simplex virus
Infection can occur without clinical lesions (and often does), and virus may still be shed
HSV-1 spread by saliva/secretions and HSV-2 spread by sexual contact → viral replication at skin/mucous membrane → retrograde axonal flow to dorsal root ganglia → latency and subsequent reactivation
HSV can evade host immune system (e.g., ↓expression of CD1a by APCs, ↓TLR signaling)
Reactivation triggers: stress, UV (UVB > UVA), fever, injury (e.g., chemical peel or fractionated laser), and immunosuppression
Grouped/clustered vesicles on a red base and Can become pustules, erosions (with classic scalloped borders due to coalescence), and ulcers, ultimately crusting over and healing within 6 weeks
Herpes simplex virus
Widespread, sometimes severe HSV infection in areas of atopic dermatitis, Hailey-Hailey, or Darier’s disease (Fig. 5-2) +/− systemic symptoms, lymphadenopathy, may be life-threatening; ↑in children
Increased with filaggrin mutations
Usually HSV-1; associated with Th2 shift in immune system
Increased in patients with severe atopic dermatitis w/ onset <5 years old, ↑IgE levels, ↑eosinophils, and food/environmental allergies
Have been associated with topical calcineurin inhibitors
Eczema herpeticum
Infection of digits (HSV-1 in children and HSV-2 in adults) w/ vesiculation/pain/swelling; recurrence seen; bimodal peaks at <10 years old and 20 to 40 years old
Herpetic whitlow
HSV-1 infection 2° to athletic contact (classically on lateral neck/side of face and forearm)
Herpes gladiators
Follicle-based vesicles/pustules in beard-area (HSV-1)
HSV folliculitis (herpetic sycosis)
Keratoconjunctivitis w/ lymphadenopathy and branching dendritic corneal ulcer; blindness may occur (HSV-2 in newborns; HSV-1 otherwise)
Ocular HSV
Most common fatal viral encephalitis in the United States (>70% die without tx); can be associated with mutations in TLR-3 or UNC-93B; usually HSV-1; fever/altered mentation/strange behavior; temporal lobe #1 site
HSV encephalitis
Histology: intraepidermal vesicle + slate-gray enlarged keratinocytes (ballooning degeneration) which are multinucleated with margination of chromatin
+/− Cowdry A inclusions (eosinophilic inclusion bodies) within nucleus, epidermal necrosis, multicellular dermal infiltrate, and perivascular cuffing
Herpes simplex virus
Most common cause of EM minor
HSV-1
Varicella zoster virus (HHV-3)
Varicella is the 1° infection and herpes zoster is the reactivation of the latent infection (more common in immunosuppressed and elderly and can → death
Pathogenesis: Varicella zoster virus
Transmitted via aerosolized droplets and direct contact with lesional fluid
Contagious from 1 to 2 days before lesion develops in varicella until all lesions crusted over
After primary varicella infection, VZV travels to dorsal root ganglion and stays dormant – if reactivated later will replicate, travel down sensory nerve to the skin, and present as herpes zoster
More severe disease in adolescents and adults
Prodromal symptoms: fever, fatigue, and myalgias
Cephalocaudal progression of classic lesions described as “dew drops on rose petal:” vesicles on an erythematous base that become pustular, then crust over
Crops of lesions in various stages
Vaccine-associated varicella zoster may rarely develop after the vaccine is administered – represents mild case of chickenpox that may start at injection site
Primary Varicella
Cutaneous scarring; CNS/ocular/limb anomalies; risk greatest if infection occurs during first 20 weeks of gestation; exposed fetus may develop reactivation (herpes zoster) in childhood
Congenital varicella syndrome
Perinatal varicella transmission (within 5 days before delivery until 2 days postdelivery); disease is severe (up to 30% mortality) because of the lack of protective maternal antibodies
Neonatal varicella
Prodrome (itch, tingling, hyperesthesia, and pain) → painful grouped vesicles on red base in a dermatomal pattern; Trunk = most common location
Herpes zoster
Oain, potentially chronic, after lesions have cleared in Herpes zoster; more common, severe and chronic in elderly
Postherpetic neuralgia
Dermatomal disease + >20 lesions outside of dermatome +/− visceral involvement; almost exclusively seen in immunosuppressed (AIDS, lymphoreticular malignancy, long-term immunosuppressive medication use, etc.); increased risk of life-threatening pneumonitis and encephalitis
Disseminated Herpes zoster
Disease of geniculate ganglion of facial nerve (CN-VII) may → ear pain, vesicles on tympanic membrane and EAM; ipsilateral facial nerve paralysis, dry mouth/eyes, anterior 2/3 tongue taste loss, and auditory (e.g., deafness and tinnitus) and equilibrium issues (vestibulocochlear nerve)
Ramsay-Hunt syndrome
Ivolvement of the side and tip of nose: indicates disease of the external division of the V1 nasociliary branch; may → to ocular involvement (e.g., keratitis, uveitis, acute retinal necrosis, and visual loss) 3/4 of time
Hutchinson’s sign
Treatment: Primary varicella
Treatment with systemic acyclovir or valacyclovir within 3 days of lesion onset → ↓severity/duration disease
Oral administration appropriate in healthy children/adults
IV acyclovir in immunocompromised patients
Post-exposure prophylaxis: Varicella
Varicella vaccine may be given within 72 to 120 hours of exposure in nonimmune, immunocompetent individuals >12 months
VZIg (Varicella zoster immunoglobulin) should be administered within 96 hours of exposure in immunocompromised, pregnant females, and neonates
IVIg may alternatively be administered
Oral acyclovir can be administered within 7 to 10 days of exposure
Varicella vaccination
Live attenuated virus recommended as a 2 dose vaccination series; part of primary immunization series
Initial dose at 12 to 15 months, booster dose at 4 to 6 years
Contraindicated in pregnancy and in immunocompromised patients
Treatment: Herpes zoster
Antiviral treatment with acyclovir (IV form in immunosuppressed), famciclovir, or valacyclovir is best given within 72 hours; prednisone helps with acute pain but has no effect on course or development of PHN
↓duration of lesions/pain
↓rate of postherpetic neuralgia (PHN) in patients >50 years old
Valacyclovir and famciclovir preferable to acyclovir
Causes infectious mononucleosis plus many other disorders (e.g., oral hairy leukoplakia, hydroa vacciniforme, Gianotti-Crosti syndrome, genital ulcers, and various hematologic disorders/malignancies (e.g., Burkitt’s lymphoma, NK/T-cell lymphoma, post-transplant lymphoproliferative disorder, and nasopharyngeal carcinoma)
Epstein-Barr virus (HHV-4)
Pathogenesis: Epstein-Barr virus (HHV-4)
transmission via saliva/blood → infects mucosal epithelial cells initially → B-cells (where virus can lay dormant and evade immune system via production of EBNA-1 protein and latent membrane protein-2)
Incubation period of 1 to 2 months; symptoms develop with viral replication
In patients with ↓cell-mediated immunity, infected B-cells may continue to replicate → lymphoproliferative disorders (cell-mediated immunity appears to be more important than humoral, conferring immunity after first mononucleosis episode)
Typically young adults w/ pharyngitis, fever, and cervical lymphadenopathy
Splenomegaly (and possible rupture) +/− hepatomegaly
↑LFTs in subset of patients
Lymphocytosis (up to 40% atypical lymphocytes)
May have nondistinct polymorphous (e.g., urticarial, morbilliform) eruption in 5% to 10% occurring within first week of illness
Centrifugal spread
Petechial lesions on eyelid and hard/soft palate junction +/− genital ulcers (esp. females)
Ampicillin/amoxicillin → “hypersensitivity” skin reaction (itchy generalized morbilliform eruption → desquamation)
Infectious Mononucleosis
Corrugated white plaque typically on lateral tongue, with strong HIV association; more common in smokers
Oral hairy leukoplakia
Nonspecific, confirms presence of IgM heterophilic antibodies which are often present in EBV infection and may persist for months after infection; 85% of older children/adults are positive during second week of infection, but is often negative in younger children
Monospot test
Higher sensitivity in younger children; can be useful in determining current vs prior infection for diagnosis of EBV
EBV-specific antibodies
Treatment: Epstein-Barr virus (HHV-4)
Supportive care
Oral corticosteroids may be considered for severe cases of tonsillitis
Avoid contact sports until splenomegaly resolves (risk for splenic rupture)
Rare sequelae: upper airway obstruction, aseptic meningitis, meningoencephalopathy, myocarditis, pericarditis, and renal failure
Transmitted via body fluids, fomites, vertical transmission, transplanted organs, and hematopoietic stem cells
Cytomegalovirus (HHV-5)
Pathogenesis: Cytomegalovirus (HHV-5)
Infects leukocytes → dissemination → various organs → latency
Most infections are asymptomatic in healthy adults; however, can cause severe disease in utero (TORCH), or in immunosuppressed/transplant patients (CMV retinitis/blindness, meningoencephalitis, pneumonitis, GI ulcers)
After the 1° infection, very low risk of reactivation, except for immunocompromised patients
Mononucleosis-like presentation (e.g., sore throat, fever, lymphadenopathy, and hepatosplenomegaly) may be associated with nonspecific exanthem (e.g., morbilliform)
If ampicillin given → eruption (as in infectious mononucleosis)
Recalcitrant ulcers of perineum or leg in HIV patients; these patients may also get verrucous plaques, vesicles, and/or nodules
Cytomegalovirus (HHV-5)
Histology of ulcers may show enlargement of endothelial cells with pathognomonic “owl’s eye” (intranuclear) inclusions
Cytomegalovirus (HHV-5)
One of the most common viral exanthems of childhood; up to 15% of infants may develop febrile seizures, but otherwise follows a generally benign course in healthy patients, 95% are between 6 months to 3 years of age
HHV-6 (Roseola infantum, exanthem subitum, sixth disease)
Virus remains latent in T cells for life → reactivation has been a/w pityriasis rosea (along with HHV-7) and DRESS syndrome (along with EBV, CMV and HHV-7)
HHV-6 (Roseola infantum, exanthem subitum, sixth disease)
Lymphotropic virus that shares significant homology with HHV-6 and may participate in co-infection w/HHV-6
Although not definitively causative of any disease, it has been a/w pityriasis rosea (along with HHV-6), and a subset of exanthem subitum cases (co-infection with HHV-6; unique clinical presentation)
HHV-7
Etiologic factor for Kaposi sarcoma – discussed in Neoplastic Dermatology chapter
Also associated with multicentric Castleman disease, primary effusion lymphoma (PEL), and paraneoplastic pemphigus
HHV-8
Infection via respiratory tract → 7 to 17 days incubation period → 1 to 4 days prodromal period (fever, headache, myalgias, and malaise) → centrifugal (face/arms/legs > trunk) vesiculopustular eruption and may involve hands/feet (lesions in any given anatomic region will be in same stage) w/ lethargic/“toxic” appearance
Rash: macule → papule → vesicle → pustules; typically scarring
Lesions first appear on palms/soles
Patients infectious from eruption onset till 7 to 10 days posteruption
Oral lesions (tongue, mouth, and oropharynx) often appear before cutaneous by lesions 1 day
Smallpox (Variola virus; Orthopox genus)
Used for live smallpox vaccine
SEs: lymphadenopathy, ocular vaccinia, generalized vaccinia, vesiculopustular/urticarial/morbilliform eruption, eczema vaccinatum (in patients with atopic dermatitis, Darier’s, or Hailey-Hailey disease), erythema multiforme, postvaccinial CNS disease, and progressive vaccinia (immunosuppressed patients; can → death)
Vaccinia (Vaccinia virus; genus = Orthopox)
Can spread via cutaneous inoculation or inhalation (hosts are monkeys, rodents, or humans)
Prodrome (fever/sweating/chills) → smallpox-like lesions, but usually milder/fewer lesions
Lesions may present in various stages and favor face and extremities (esp. palms/soles), with centrifugal spread; may scar
May have systemic symptoms (respiratory, fever, and LAD in 67%)
Central/western Africa, though United States outbreak from prairie dogs
Monkeypox (Monkeypox virus; genus = Orthopox)
Spread via cutaneous contact (hands and face) with infected animal (usually cats)
Incubates 7 days → painful red papule at contact site → vesicular → pustular → hemorrhagic → ulcer w/ eschar
Lesions usually solitary and occur on hands/fingers
Can have LAD, and fever
Europe and Asia
Cowpox (Cowpox virus; genus = Orthopox)
Develop one to few lesions at contact site (usually hands) as a result of contact with infected animals (sheep, goats, or reindeer; usually on udders/perioral areas of ewes)
RFs: certain jobs (shepherds, butchers, and veterinarians)
Self-resolves
Diagnosis via histology (depends on stage) or PCR
Orf (ecthyma contagiosum; Orf virus; genus = Parapox)
Papules at site of contact (usually muzzles of calves and teats of cows) on distal upper extremities usually with single lesion(s), which look like orf
Most common in farmers/ranchers, veterinarians, and butchers
Diagnosis via histology or PCR
Milker’s nodules (“Pseduocowpox;” Paravaccinia virus; genus = Parapox)
Common infection in school-aged children; may be sexually transmitted in adolescents/adults; spread by contact with infected skin or fomites, or possibly via water
Cause by molluscipox infection with two subtypes: MCV-I and MCV-II
Prototypical lesion is an umbilicated, pink, and pearly papule most common on intertriginous areas, torso, lower extremities, and buttocks
Lesions can become widespread in patients with impaired skin barrier (atopic dermatitis or ichthyosis) or immunodeficiency (chemotherapy-induced or HIV; may also see giant molluscum lesions)
Molluscum contagiosum (Molluscum contagiosum virus [MCV]; genus = Molluscipox
Six lesion stages of Orf
maculopapular (umbilicated) → targetoid → acute (weeping nodule) → regenerative (nodule w/ thin crust and black dots) → papillomatous → regressive (crust overlying resolving lesion)
Histology: Henderson-Patterson bodies within dermis
Molluscum contagiosum
Treatment: Molluscum contagiosum
Cryotherapy, cantharidin, extraction/curettage, cimetidine, candida antigen immunotherapy, topical retinoids, and imiquimod
Self-limited with resolution after weeks to years of infection
≤50% of newly infected patients; presents in conjunction with classic mononucleosis-like syndrome of primary HIV infection, typically within 6 weeks of transmission
Rash may be limited or widespread, is often asymptomatic, and is typically characterized by ill-defined erythematous maculopapules
Acute exanthem of primary HIV infection
Characterized by eosinophil-rich inflammatory infiltrate in or around hair follicles
Intensely pruritic, erythematous, and follicularly based papules located on the upper trunk, face, neck, and scalp
Eosinophilic folliculitis
Lesions most often occur on mobile, nonkeratinized oral mucosal surfaces, but esophageal and anogenital aphthae are not uncommon in HIV patients
Treatments: topical anesthetics, potent topical steroids, intralesional steroids, systemic corticosteroids, and thalidomide (severe or refractory disease)
Aphthous stomatitis
In HIV, often associated with β-hemolytic strep infection
Dapsone = treatment of choice
Oral antibiotics indicated for Streptococcus-associated cases
Erythema elevatum diutinum
Intensely pruritic condition commonly seen in patients with advanced HIV in developing world
May represent aberrant immunologic response to insect bites or reactivation of prior bites
Patients present with extensive, skin-colored-to-hyperpigmented, excoriated papules
Pruritic papular eruption
Group of photodistributed rashes with multiple clinical manifestations including lichenoid (most common), eczematous, hyperpigmented, and vitiliginous
Exposure to certain photosensitizing medications, particularly trimethoprim-sulfamethoxazole, can increase risk
Treatment difficult; strict photoprotection and topical steroids; thalidomide in refractory cases
HIV photodermatitis
Pathologic inflammatory response to preexisting antigen that develops soon after initiation of antiretroviral therapy in the setting of decreasing viral load, +/− corresponding increase in CD4+ counts; Most commonly occurs 2 weeks to 3 months after initiation of antiretroviral therapy; rarely require discontinuation of antiretroviral therapy – findings typically improve/resolve after several months
Immune reconstitution inflammatory syndrome (IRIS)
HIV-Associated Dermatoses >500 cells/mm3
Acute exanthema of primary HIV infection
Seborrheic dermatitis
Oral hairy leukoplakia
Vaginal candidiasis
HIV-Associated Dermatoses <500 cells/mm3
Psoriasis Herpes zoster HPV HSV Staphylococcal infections Oropharyngeal candidiasis
HIV-Associated Dermatoses <200 cells/mm3
Kaposi sarcoma Eosinophilic folliculitis Molluscum contagiosum Major aphthae (<100) Bacillary angiomatosis Disseminated coccidiomycosis, histoplasmosis; Cryptococcus (<100) Xerosis, eczematous dermatitis, acquired ichthyosis Crusted scabies
HIV-Associated Dermatoses <50 cells/mm3
Large, nonhealing herpes simplex related ulcerations
Giant molluscum
Pruritic papular eruption
HIV photodermatitis
Caused by protease inhibitors, nucleoside reverse transcriptase inhibitors, and to lesser extent, nonnucleoside reverse transcriptase inhibitors; manifest as lipoatrophy (loss of fat in face, extremities, and buttocks) or lipohypertrophy (accumulation and redistribution of fat to upper back, neck, or abdomen); typically seen ≤2 years of starting therapy; associated with metabolic abnormalities (e.g., hyperlipidemia and insulin resistance)
Antiretroviral-associated lipodystrophy
Approved for treatment of antiretroviral-associated facial lipoatrophy
Poly-L-lactic acid and calcium hydroxylapatite
Can cause nail and mucocutaneous hyperpigmentation (longitudinal streaks or diffuse hyperpigmentation of fingernails/toenails)
Zidovudine
Most common antiretroviral to cause DIHS/DRESS (up to 8% patients; can be fatal); HLA-B*5701 linked
Abacavir
Most common bacterial infection in children
Impetigo
How many are carriers of S. aureus?
35% of population carry S. aureus (anterior nares>perineum>axilla, toe webs) → ↑risk impetigo
Non-bullous impetigo
70%): S. aureus (>Streptococcus pyogenes); children > adults
Most commonly see erosion + “honey-colored” crust; affects traumatized, abraded, or eczematous skin; most commonly face (perioral/perinasal); self-resolves in 2 weeks
Histology: neutrophilic microvesiculopustules, spongiosis, and Gram(+) cocci
Bullous impetigo
(30%): phage group II (types 55 and 71) S. aureus → produce exfoliatoxins A and B (ETA and ETB) → cleaves desmoglein 1 → subcorneal/intragranular acantholysis
Children > adults; presents with (p/w) flaccid bullae + erosions w/ collarette of scale, minimal surrounding erythema; affects intact skin, has more generalized distribution
Histology: subcorneal/intragranular acantholysis, neutrophils in blister cavity, Gram(+) cocci
Treatment: Impetigo
Localized: topical Mupirocin, retapamulin, or fusidic acid
Widespread: oral β-lactamase resistant PCN or first generation CSN or clindamycin
Complicated: IV ceftriaxone
Used for patients w/ recurrent infections; topical mupirocin BID to nares for 7 to 10 days +/− skin decolonization w/ mupirocin ointment or chlorhexidine washes
Decolonization
Most common form of bacterial folliculitis; most commonly on face (beard area typically)
S. aureus folliculitis
S. aureus folliculitis - Superficial form (Bockhart’s impetigo)
small papulopustules on erythematous background
S. aureus folliculitis - Deep form (“sycosis barbae”)
large red papulopustules +/− plaques with small pustules
Bacterial folliculitis seen in acne patients on long-term ABX
Gram(-) folliculitis
Bacterial folliculitis a/w poorly chlorinated hot tubs/whirlpools
Pseudomonal folliculitis
T/F: No risk of rheumatic fever from streptococcal impetigo
True
Collections of pus, most commonly from S. aureus (often MRSA); may be complicated by surrounding cellulitis/phlebitis
Abscesses/Furuncles/Carbuncles
Inflamed and fluctuant nodule; arises on any site
Abscess
Only occurs in a/w hair follicles/on hair-bearing sites (“FURuncle = FURry sites”); head/neck (#1 site) >intertriginous zones, thighs, other sites of friction
Furuncle
Collection of furuncles, often deeper w/ multiple draining sinuses; most often affects thick skin of posterior neck, back, and thighs; systemic symptoms typically present
Carbuncle
Most common cause of purulent infections presenting to ED; most commonly p/w furunculosis mistaken clinically for “spider bite”; may be a/w cellulitis, and necrotic plaques (>necrotizing fasciitis and toxic shock syndrome)
MRSA
Pathogenesis: MRSA
Resistance because of mecA gene (encodes penicillin-binding protein, PBP2a) →↓affinity for β-lactams
Pathogenesis: CA-MRSA
Also has Panton-Valentine leukocidin (PVL) virulence factor; a/w increased virulence, leading to more severe necrosis of skin and other tissues
Most commonly infants/young children (low mortality, <5%) who lack neutralizing antibodies and have ↓renal clearance
Also seen in adults w/ CRF (high mortality, >50%); M > F (2–4 : 1)
p/w febrile prodrome, widespread skin tenderness; skin eruption begins on face (periorificial radial fissuring) and intertriginous zones → generalizes within 48 hours as wrinkled-appearing skin w/ flaccid bullae and (+)Nikolsky sign → desquamation continues for up to 1 week, then heals without scarring
Staphylococcal scalded skin syndrome (SSSS)
Pathogenesis: Staphylococcal scalded skin syndrome (SSSS)
Infection by phage group II (types 55 and 71) S. aureus at a different/distant site → production of exfoliatoxins A & B (ETA, ETB)→exfoliatoxins disseminate via bloodstream→widespread cleavage of Dsg1 → subcorneal/intragranular acantholysis
Histology: Staphylococcal scalded skin syndrome (SSSS)
Resembles P. foliaceus; lacks inflammatory cells and bacteria in blisters (vs bullous impetigo)
Treatment: Staphylococcal scalded skin syndrome (SSSS)
Mild disease: β-lactamase resistant PCN (dicloxacillin) or first generation CSN (cephalexin)
Severe disease: hospitalization + IV ABX
T/F: Most common primary sites of infection in children = nasopharynx or conjunctivae
True
Severe multisystem disease with cutaneous and internal involvement (renal > GI, MSK, CNS, hepatic, hematologic, and mucosal); typically affects young, healthy adults; occult primary site of infection; p/w high fever (>102°F) + rash + systemic symptoms + hypotension (100%)
Staphylococcal toxic shock syndrome (S-TSS)
Menstrual TSS
<50% of cases; young women w/ superabsorbent tampons; mortality rate less than 5%
Nonmenstrual TSS
> 50%; M = F; a/w nasal packing, surgery, skin, or internal infections; mortality rate <20%
Mucocutaneous eruption classically starts w/ scarlantiniform eruption (initially on trunk → becomes generalized), redness and edema of palms/soles, “red strawberry tongue,” conjunctival hyperemia → palmoplantar desquamation (1 to 3 weeks later), Beau’s lines, onychomadesis; usually negative blood cultures (<15% positive); low mortality
Staphylococcal toxic shock syndrome (S-TSS)
Pathogenesis: Staphylococcal toxic shock syndrome (S-TSS)
Production of toxic shock syndrome toxin-1 (TSST-1) by certain strains of S. aureus → TSST-1 acts as superantigen, binding to Vβ region of TCR and class II MHC on APCs → nonspecific activation of T-cells + cytokine storm (↑TNF-α, IL-1, IL-6, TLR2, and TLR4)
Treatment: Staphylococcal toxic shock syndrome (S-TSS)
β-lactamase resistant ABX, clindamycin (suppresses toxin production) +/− IVIG; IV fluids for hypotension
T/F: Staph-TSS has lower mortality (3%–20% vs 30%–60%) vs Strep-TSS
True
S. aureus infection of skeletal muscle; usually have predisposing factors (immunosuppression, diabetes, trauma, and IVDA); p/w 1 to 2 week febrile prodrome, muscle pain, and a soft tissue mass w/ surrounding woody induration → muscle abscess +/− septicemia
Pyomyositis
Best diagnostic tool for S aureus Pyomyositis
MRI
Deep granulomatous and suppurative infection most frequently caused by S. aureus; may extend to skeletal muscle and bone; affects all ages; a/w ↓T-cell counts and other defects in cellular immunity; 70% have skin-limited disease (rarely visceral in severely immunosuppressed patients; lung most common); p/w deep, ulcerative plaques/nodules with multiple draining sinuses that drain yellow granules
Botromycosis
Histology: Botromycosis
Large granules w/ basophilic center (nonfilamentous bacteria) and eosinophilic/hyaline periphery (Splendore-Hoeppli phenomenon; comprised of IgG and C3 deposits), granules are surrounded by abscess and granulomatous inflammation; granules are PAS(+), Giemsa(+), and Gram(+)
Treatment: Botromycosis
Surgical debridement + antistaphylococcal antibiotics
Deep variant of impetigo; most common in children; caused by Streptococcus pyogenes; p/w few vesicopustules, most commonly on legs → develop into “punched-out” ulcers with purulent base and hemorrhagic crust → slowly self-resolves w/ scarring; frequently as a result of scratching bug bites
Ecthyma
Histology: Ecthyma
Well-circumscribed ulcer w/ overlying impetiginized scale crust and dense underlying dermal neutrophilic inflammation
Treatment: Ecthyma
β-lactamase resistant PCN (dicloxacillin) or first generation CSN (cephalexin)
More superficial variant of cellulitis (upper-mid dermis vs deep dermis/SQ) with sharply defined (“ridge-like”) borders, fiery-red color, and pain or burning sensation; prominent lymphatic involvement; most common sites = lower extremity (#1 site) > face; lymphedema is major risk factor; caused by group A β-hemolytic strep
Erysipelas (“St. Anthony’s Fire”)
Diagnosis: Erysipelas
Wound/blood cultures usually negative; best confirmatory tests = ↑DNase B and ASO titers
Treatment: Erysipelas
Penicillin (treatment of choice) for 10 to 14 days; erythromycin if PCN-allergic
Classically boys >4 years old; p/w sharply defined red plaques spreading up to 3 cm from anus; a/w pain upon defecation, blood in stool, guttate psoriasis outbreak
Labs: skin culture confirmatory
Perianal streptococcal skin infection
Treatment: Perianal streptococcal skin infection
Oral cefuroxime (treatment of choice) or penicillin (slightly less effective)
Initially p/w darkening of skin of distal finger (>toe) volar fat pad → progresses to purulent vesicle/bulla on erythematous background within 1 week; affects children; as a result of picking of nose or local skin trauma; S. pyogenes > S. aureus
Blistering distal dactylitis
Treatment: Blistering distal dactylitis
I&D + 10-day course oral β-lactam
Affects young children (1–10 years old); caused by group A β-hemolytic streptococcus → produces streptococcal pyrogenic toxins A, B, and C (SPE-A, B, and C); most commonly in setting of streptococcal pharyngitis/tonsillitis; p/w sore throat, high fevers, and systemic symptoms → 1 to 2 days later, macular erythema on upper trunk/neck → soon develop classic “sandpaper-like” papular eruption, Pastia’s lines (linear petechiae; favors flexural sites), flushed cheeks with circumoral pallor, and “white strawberry tongue” (white background + red papillae) → later “red strawberry tongue,” purulent exudate from throat → 1 to 2 weeks later, palmoplantar desquamation
Scarlet Fever
Treatment: Scarlet Fever
PCN (treatment of choice), amoxicillin, or erythromycin (if PCN allergic)
Complications: Scarlet Fever
Acute glomerulonephritis
Rheumatic fever
Affects young/healthy adults, is more severe w/ higher mortality (30%–60%), usually a/w florid skin/soft-tissue infections (often necrotizing fasciitis vs occult infections in Staph-TSS), much less frequent generalized macular erythematous rash, and far more frequent blood culture positivity (>50%)
Streptococcal toxic shock syndrome
Most common primary source of Streptococcal toxic shock syndrome
Skin infection from skin barrier breakdown (excoriation, bug bite, and infected surgical site)
Classically p/w severe localized pain in extremity w/ redness, swelling or necrotizing fasciitis → within 24 to 48 hours, systemic symptoms (hypotension [100%])
Streptococcal toxic shock syndrome
Pathogenesis: Streptococcal toxic shock syndrome
Group A β-hemolytic strep (M types 1 and 3) produce various toxins:
SPE A, B, and C
Streptococcal mitogenic toxin Z (SMEZ)
Streptolysin O
Toxins act as superantigens, binding to Vβ region of TCR and class II MHC on APCs → nonspecific activation of T-cells + cytokine storm (↑TNF-α, IL-1, IL-6, TLR2, and TLR4)
Treatment: Streptococcal toxic shock syndrome
Most cases severe, requiring hospitalization + surgical debridement of soft-tissue infection (possibly fasciotomy or amputation) + clindamycin (inhibits toxin production) + PCN +/− IVIG
Infection of deep dermis/SQ most commonly affecting adults w/ skin barrier disruption; p/w tender/red/warm, ill-defined plaques w/ fever/chills/lymphangitis, in severe cases, may see necrosis, bullae, vesicles; most commonly caused by group A β-hemolytic strep > S. aureus (most common cause in children); most common sites: head/neck (children), lower extremities (adults), and IV injection sites on arms (IVDA)
Cellulitis
Treatment: Cellulitis
Uncomplicated cases: oral dicloxacillin, cephalexin, or clindamycin for 10 days (must empirically cover for Staph and Strep)
Cellulitis a/w diabetic/decubitus ulcers: piperacillin/tazobactam, or ciprofloxacin + metronidazole
Severe cases: hospitalize and IV antibiotics
MRSA cellulitis: TMP/SMX, minocycline/doxycycline, and clindamycin
Rapidly progressive, life-threatening (up to 50% mortality) necrotizing infection of skin, SQ, and fascia; most common site = extremities (>trunk); caused by group A β-hemolytic strep M types 1 and 3 (#1 cause in children) or polymicrobial (#1 cause in adults; mixture of Streptococci, S. aureus, E. coli, Clostridium, and Bacteroides)
Necrotizing fasciitis
Initially p/w severely painful indurated/”woody” plaque (“pain out of proportion to visible skin changes”) → over 1 to 2 days and rapidly progresses → color changes from erythematous → dusky purple/gray +/− hemorrhagic bullae/ulceration, crepitus, foul-smelling discharge; patients always severely toxic-appearing (fever, tachycardia, and septic shock) → late in course and skin becomes anesthetic (nerves destroyed)
Necrotizing fasciitis
Necrotizing fasciitis of genitalia/perineum/lower abdominal wall
Fournier’s gangrene
Polymicrobial Necrotizing fasciitis arising as a postoperative complication
Meleney’s gangrene
Treatment: Necrotizing fasciitis
Fasciotomy + IV abx (piperacillin/tazobactam + clindamycin + ciprofloxacin)
Risk factors: Necrotizing fasciitis
Diabetes Immunosuppression PVD CRF Trauma IVDA Recent surgery
Prognostic factors a/w ↑mortality: Necrotizing fasciitis
Older age ↑time to first debridement ↑extent of infection Females ↑lactic acid ↑creatinine
Caused by C. minutissimum (Gram(+) filamentous rod)
Affects stratum corneum of moist, intertriginous zones (groin and toe webs (particularly fourth) > axillae, inframammary, umbilicus, and intergluteal)
Fluoresces “coral red” w/ Wood lamp (bacterial coproporphyrin III production)
Groin: light red-pink slightly scaly patches w/ thin scale
Toe webs: chronic, asymptomatic fissuring and maceration
Histology: filamentous Gram(+) rods within stratum corneum
Erythrasma
Treatment: Erythrasma
Localized: 20% aluminum chloride, topical clindamycin/erythromycin
Widespread/recalcitrant: oral erythromycin and tetracyclines
Caused by Kytococcus sedentarius, which digests keratin in stratum corneum
Noninflammatory infection of weight-bearing areas of plantar (>palmar) skin
p/w small crateriform pits and foul odor → may coalesce into arciform pits
RFs: hyperhidrosis and occlusion
Histology: sharply demarcated, deep pits in stratum corneum with Gram(+) bacteria at base of pits
Pitted Keratolysis
Treatment: Pitted Keratolysis
Topical erythromycin (or clindamycin, mupirocin, and azole antifungals) +/− 20% aluminum chloride, or botulinum toxin for hyperhidrosis
Asymptomatic, adherent yellow-red concretions on axillary hair shafts; fluoresces with Wood lamp; caused by Corynebacterium tenuis
Trichomycosis axillaris
Treatment: Trichomycosis axillaris
Shaving of axillary hair (treatment of choice); may use topical erythromycin/clindamycin
Very rapid, potentially fatal necrotizing soft tissue infection with localized gas production (“gas gangrene”); caused by Clostridium perfringens (Gram(+), spore-forming rod) - obligate anaerobe (only reproduces in hypoxic tissues)
Clostridial anaerobic cellulitis and myonecrosis
Due to traumatic inoculation (surgery or crush/penetrating injuries) of C. perfringens into oxygen-poor deep tissues; bacteria produces two pathogenic toxins: α-toxin (cleaves lipids) and perfringolysin (induces vascular clots and worsens tissue hypoxia) → bacteria proliferates freely in anaerobic environment, producing CO2 and cleaving lipids → clinically p/w crepitus, foul-smelling brown exudate (“dirty dishwater” color), w/ variable skin changes
RFs: diabetes, PVD
Clostridial anaerobic cellulitis and myonecrosis
Treatment: Clostridial anaerobic cellulitis and myonecrosis
Immediate aggressive surgical debridement (most important) + clindamycin and third gen CSN +/− hyperbaric oxygen
Agent: Actinomycosis
Actinomyces israelii
Caused by gram(+), nonacid fast, and anaerobic/microaerophilic filamentous bacteria which are part of normal flora of mouth, GI/GU tracts → infection arises after trauma (dental procedures or surgical interventions); subacute-chronic granulomatous lesions with suppurating abscesses + sinus tracts
Actinomycosis
Most common form of Actinomycosis, accounts for 70%): “lumpy jaw disease,” red-brown nodules with fistulous abscesses draining characteristic yellow sulfur
Cervicofacial Actinomycosis
Histology: Actinomycosis
Dense granulomatous and suppurative inflammation with “granules” with basophilic center (Gram(+) branching filaments of Actinomyces) and eosinophilic rim (Splendore-Hoeppli phenomenon)
Treatment: Actinomycosis
Penicillin G or ampicillin
Chronic or deep-seated infections: 2 to 6 weeks of IV abx followed by 3 to 12 months of oral PCN
Acute infections: 2 to 3 weeks of oral PCN + I&D of abscesses + surgical excision of sinus tracts
Half of all cases are caused by the Gram(+), weakly acid-fast, filamentous bacteria; traumatic inoculation causes a painless nodule that enlarges, suppurates, and drains via the sinus tracts; purulent discharge contains sulfur granules; foot is the usual site of involvement but may involve underlying muscle and bone
Nocardiosis
Histology: Nocardiosis
Intense neutrophilic infiltrate + sulfur granules (only seen in actinomycotic mycetoma form); branching filaments are Gram(+), AFB+ (Fite > Ziehl-Neelsen), and GMS+
Treatment: Nocardiosis
Sulfonamides (treatment of choice) +/− surgical drainage
Agent: Bacillus anthracis - Gram(+), spore-forming rod
Anthrax
Arises via occupational exposure (“Woolsorter’s disease”) from direct contact w/ infected animals/carcasses and presents 1 week postexposure with purpuric papulovesicle (“malignant pustule”) that drains serosanguinous fluid → vesicle ulcerates to form painless/black/necrotic eschar w/ satellite vesicles and edema; most common and least lethal form
Cutaneous anthrax
Treatment: Anthrax
First line (cutaneous anthrax): quinolone or doxycycline ×2 weeks (treat for 60 days if suspect bioterrorism or possible inhalation exposure)
Virulence factors: Anthrax
- Poly-D-glutamic acid capsule (resists phagocytosis)
- Lethal toxin = protective antigen + lethal factor (↑TNF-α and IL-1β → septic shock, death)
- Edema toxin = protective antigen + edema factor (↑cAMP → edema)
Acute, self-limited infection; occupational disease of fisherman or poultry/fish handlers; as a result of traumatic inoculation of Erysipelothrix rhusiopathiae (Gram(+) rod); most commonly p/w localized form: red-violaceous nonsuppurative cellulitis +/− hemorrhagic vesicles; classically affects finger web spaces w/ sparing of terminal phalanges
Erysipeloid
Treatment: Erysipeloid
Penicillin (treatment of choice), ciprofloxacin (if PCN allergic)
Most commonly affects pregnant women, elderly, and the immunosuppressed as GI illness caused by the ingestion of Listeria monocytogenes (motile Gram(+) rod) → fever, bacteremia, and meningitis; rarely see skin lesions – mostly occurs in setting of neonatal septicemia (from vertical transmission), which p/w disseminated papules/pustules/vesicles
Listeria
Treatment: Listeria
First line: ampicillin
Second line: TMP/SMX
Green/blue-black nail discoloration; a/w excessive water exposure, nail trauma; from P.aeuruginosa pyocyanin pigment production
Green nail syndrome
Treatment: Green nail syndrome
Topical quinolone, vinegar soaks, or aminoglycoside solution × 4 months
Superficial erosive infection w/ blue-green purulent exudate, “moth-eaten” appearance to skin surface, with “mousy” or “grape-like” odor; may arise at burn sites, in mixed toe web infections, and other chronic wounds
Pseudomonal pyoderma
Treatment: Pseudomonal pyoderma
Systemic antipseudomonal antibiotics, topical antiseptics, debridement, and drying agents
P. aeuruginosa infection of external auditory canal; p/w edema, skin maceration, and purulent green exudate; tympanic membrane intact; classically severe pain upon pinna manipulation
Otitis externa (“swimmer’s ear”)
Severe variant of otitis externa usually only in diabetics or immunosuppressed; persistent drainage w/ excessive granulation tissue extending to bony portion of ear → may result in osteomyelitis of skull base
Malignant otitis externa
Self-resolving P. aeuruginosa infection arising from poorly chlorinated hot tubs/whirlpools; p/w red, perifollicular papulopustules 1 to 2 days postexposure; commonly affects areas covered by bathing suit; spontaneously resolves within 2 weeks
Pseudomonal folliculitis (“hot tub folliculitis”)
Self-resolving P. aeuruginosa infection arising from wading in pools w/ high concentrations of Pseudomonas; p/w painful, red-violaceous plaques/nodules on weight-bearing areas of plantar surface
Histology: identical to idiopathic palmoplantar hidradenitis
Pseudomonas hot-foot syndrome
Cutaneous lesion indicative of P. aeuruginosa septicemia; most commonly occurs in immunosuppressed patients w/ severe neutropenia (often BMT patients); p/w a small number of purpuric macules → progresses to hemorrhagic bullae → bullae rupture → ulcer w/ necrotic black eschar and tender, red skin surrounding eschar; most common sites = anogenital region and extremities
Histology: sharply demarcated epidermal necrosis w/ hemorrhagic crust, and underlying dermal infarction w/ septic vasculitis (Gram(-) rods in vessel walls)
Ecthyma Gangrenosum
Treatment: Ecthyma Gangrenosum
IV aminoglycoside + antipseudomonal PCN
Prognostic factors a/w poor outcome in Ecthyma Gangrenosum
↑# lesions
Delay in diagnosis
Prolonged neutropenia
Small, facultative intracellular Gram(-) bacilli that cause that can cause cat scratch disease, bacillary angiomatosis, peliosis hepatitis, trench fever, and Carrion’s disease/Oroya fever/verruga peruana
Bartonella
Bartonellosis (Carrion’s disease, Oroya fever, and verruga peruana)
Bartonella bacilliformis
Vector: Bartonellosis
Phlebotomine sand fly (Lutzomyia verrucarum)
Reservoir/host: Bartonellosis
Human
Treatment: Oroya fever (acute phase)
1st line - Chloramphenicol* plus β-lactam antibiotic
Quinolone (norfloxacin and ciprofloxacin) (>6 years of age and not pregnant)
2nd line - Trimethoprim–sulfamethoxazole
Macrolide
Doxycycline
Treatment: Verruga peruana (chronic phase)
1st line - Rifampin + streptomycin (traditional)
2nd line - Ciprofloxacin Azithromycin
Cat scratch disease
Bartonella henselae
Vector: Cat scratch disease
Cat flea (Ctenocephalides felis)
Reservoir/host: Cat scratch disease
Cat
Treatment: Cat scratch disease
Mild to moderate, uncomplicated - Supportive care (analgesics) only Azithromycin Doxycycline plus rifampin Azithromycin (2nd line)
Severe, complicated - Doxycycline plus rifampin
Bacillary angiomatosis
Bartonella henselae
Bartonella quintana
Trench fever “Five day fever”
“Urban trench fever”
Bartonella quintana
Vector: Trench fever
Human body louse (Pediculosis humanus)
Reservoir/host: Trench fever
Human
Treatment: Trench fever
Doxycycline plus aminoglycoside
Mostly occurs in HIV + patients w/ CD4 count <200; only 20% recall cat bite/scratch (vs 90% w/ cat scratch disease); vascular proliferation caused by bacterial angiogenic factor; can involve lymph nodes, bone, and viscera; lesions are dome-shaped, vascular papulonodules but more developed lesions can have a friable eroded appearance, resembling pyogenic granulomas
Bacillary angiomatosis
Histopathology: resembles pyogenic granuloma (lobular capillary proliferation), but has dense neutrophilic infiltrate, and extra- and intracellular organisms (within endothelial cells) seen w/ Warthin-Starry stain
Verruga peruana
Bacillary angiomatosis
Small, obligate intracellular Gram(-) organisms; transmitted by arthropod host/vector (ticks, fleas, lice, and mites); target = endothelial cells
Rickettsia
Transmitted from arthropod (tick, flea, mite, and louse) via saliva or feces → bacteria enter dermis via bite or scratching → bacteria attach to endothelial cells → spread hematogenously and destroy infected vessels via reactive oxygen species formation → ↑vascular permeability → vascular skin findings (petechiae, purpura, and vasculitis = “spotted fever”) and life-threatening end organ damage (meningoencephalitis and pulmonary edema/pneumonitis most important causes of mortality), thrombocytopenia, hypovolemia, and hypotension
Rickettsia
Gram(-) diplococcus (strains A, B, C, Y, and W-135); Most commonly affects children/young adults living in close quarters (military recruits and college students); M > F (4 : 1); humans are only reservoir; 10% to 15% population are asymptomatic carriers (in nasopharynx); disease transmitted via respiratory secretions
Neisseria meningitidis
1 to 10 days postexposure, p/w fever, chills, headache, petechial rash (30%–50%), retiform purpura w/ classic “gunmetal gray” color, or hemorrhagic bullae on legs and trunk; may progress to septic shock with DIC (purpura fulminans)
Acute meningococcemia
Less common; p/w recurrent fevers, arthralgias, and macular/papular eruption; condition self-resolves, only to recur days to weeks later
Chronic meningococcemia
Treatment: Meningococcemia
First line: high-dose IV penicillin (treatment of choice)
Second line: quinolones or chloramphenicol (if PCN-allergic); third generation CSN (resistant disease)
Prophylactically treat all close contacts w/ ciprofloxacin, rifampin, azithromycin
Main virulence factor of Meningococcemia
Polysaccharide capsule
Caused by Gram(-) coccobacillus, Brucella spp.; endemic in Middle East (consuming unpasteurized goat milk/cheese). In the United States, occupational disease (farmers, butchers, and veterinarians) from direct contact or inhalationvp/w undulating fevers, arthralgias, lymphadenopathy, hepatosplenomegaly, and rare (<10%) skin findings (disseminated violaceous papules, EN)
Brucellosis (Malta fever, “undulant fever”)
Treatment: Brucellosis
Multidrug regimens of doxycycline + other antibiotics (streptomycin, rifampin, TMP/SMX, quinolones, and aminoglycosides)
Gram(-) bacillus, Burkholderia mallei caused by contact w/ infected horses or donkeys
Glanders
Forms: Glanders
Localized—hemorrhagic, ulcerative papulopustule at inoculation site
Chronic—multiple soft tissue nodules (“farcy buds”) on skin overlying lymphatics
Septicemic form—mortality rate >95% without treatment and 50% w/ treatment
Pulmonary form—mortality similar to septicemic form
Treatment: Glanders
Localized disease: 60- to 150-day course of amoxicillin/clavulanate, doxycycline, or TMP/SMX
Septicemic: IV carbapenems + ciprofloxacin or doxycycline
Gram(-) bacillus Burkholderia pseudomallei caused by direct contact w/ contaminated water or soil
RFs: diabetes, alcoholism, immunosuppression, and IVDA
Clinical presentation and mortality rates ~same as glanders
Melioidosis
Chronic granulomatous infection as a result of the inability of macrophages to kill phagocytosed E. coli
Most commonly affects immunosuppressed (BMT > HIV/AIDS)
Most commonly affects GU tract; may affect skin of perianal/genital region (ulcerated abscesses and soft polypoid lesions)
Malakoplakia (malacoplakia)
Histology: dense granulomatous infiltrate comprised of von Hansemann cells (large macrophages w/ eosinophilic cytoplasm) containing Michaelis-Gutmann bodies (round, laminated, calcified basophilic intracytoplasmic inclusions; comprised of incompletely killed bacteria within calcified phagolysosomes; stain w/ von Kossa, PAS, Perls, Giemsa)
Malakoplakia (malacoplakia)
Treatment: Malakoplakia (malacoplakia)
Localized: surgical excision
Nonsurgical candidates: difficult to treat; may try long courses of ciprofloxacin, TMP/SMX, or clofazimine
Gram(-) coccobacillus, Francisella tularensis transmitted through contact w/ rabbit carcasses (classic!), deer flies, and ticks; increased risk in hunters and animal handlers; most common presentation is ulceroglandular = 80% which p/w necrotic, punched-out ulcer at inoculation site w/ suppurative lymphadenopathy
Tularemia (rabbit fever and deer fly fever)
Treatment: Tularemia
Streptomycin (treatment of choice)
Gram(-) coccobacillus which classically affects infants, p/w deep red-violaceous/blue facial cellulitis (most commonly periorbital or buccal) following a URI-like illness; usually positive blood cultures
H. influenzae cellulitis
Treatment: H. influenzae cellulitis
Third generation CSN
Chronic granulomatous infection of nose and upper respiratory tract which affects adults, mainly in tropical locations; transmitted by inhalation of Klebsiella rhinoscleromatis; a/w cellular immune defects: inability of macrophages to kill phagocytosed bacteria → Mikulicz cells (large, vacuolated histiocytes containing bacteria)
Rhinoscleroma
Three clinical phases: Rhinoscleroma
- Catarrhal phase (rhinitis, obstruction from soft tissue edema)
- Granulomatous/infiltrative phase (granulomatous nodules in nose/URT, epistaxis, dysphonia, anesthesia of soft palate, and Hebra nose)
- Sclerotic phase (extensive scarring requires tracheotomy and nasal reconstruction)
Histology: dense pan-dermal infiltrate of Mikulicz cells containing bacteria (seen w/ Warthin-Starry, Giemsa) and Russell bodies
Rhinoscleroma
Treatment: Rhinoscleroma
Tetracycline (treatment of choice) for 6 months along with surgical correction of airway; ciprofloxacin is second line
Enteric infection caused by Salmonella typhi; spread by direct contact w/ infected individuals or carriers; p/w fever, nausea/vomiting, diarrhea, headache, and characteristic “rose spots” of skin (2- to 8-mm pink, grouped papules on trunk); bacteria can be cultured from rose spots
Salmonellosis (typhoid fever)
Treatment: Salmonellosis (typhoid fever)
Quinolones (treatment of choice); use third gen CSN in children
Caused by Streptobacillus moniliformis as a result of a rat bite (“rat bite fever”), or occasionally, ingestion of contaminated food (“Haverhill fever”); ↑incidence in urban areas w/ high rat concentration; p/w redness, edema, and ulceration at bite site → paroxysmal fever w/ systemic symptoms → 2 to 4 days later, migratory polyarthritis + acral eruption (palms and soles most common) of petechial red macules/papules, vesicles, or pustules; up to 15% mortality
Rat-bite fever (“Haverhill fever”)
Treatment: Rat-bite fever (“Haverhill fever”)
Penicillin (treatment of choice) for 1 week (6 weeks if septicemic)
Classic triad of Rat-bite fever (“Haverhill fever”)
- paroxysmal fever
- migratory polyarthritis
- acral rash
Caused by Yersinia pestis, a Gram(-) bipolar bacillus with characteristic “safety pin” appearance of bacteria on gram or Giemsa stain
Plague
Present with pustule or ulcer at inoculation site (10%) + painful, suppurative regional lymphadenopathy = “buboes” (groin, axillae most common); 25% to 50% mortality rate if untreated; most common form
Bubonic Plague
Treatment: Plague
First line: aminoglycosides (streptomycin and gentamicin)
Plague meningoencephalitis: chloramphenicol (high penetration of blood-brain barrier)
Postexposure prophylaxis: doxycycline or ciprofloxacin ×7 days (highly effective)
Most commonly affects men >40 years old who have predisposing factors: liver disease (hemochromatosis, cirrhosis, or alcoholism), diabetes (peripheral neuropathy/vasculopathy predisposes to wound infections), GI disease, immunosuppression, and ESRD
Reservoir = shellfish
Vibrio vulnificus
Two modes of infection: Vibrio vulnificus
- Cutaneous exposure to contaminated seawater/shellfish: affects shellfish handlers; trauma → primary skin infection, or superinfection of preexisting wound → may progress to necrotizing fasciitis, myositis, or septicemia
2 .Consumption of raw/undercooked shellfish: most commonly from raw oysters; septicemia, abdominal cramps, and hypotension; 75% have skin findings – red-purple macules/vesicles → progress to hemorrhagic bullae and necrotic plaques
Treatment: Vibrio vulnificus
Doxycycline + third gen CSN
Dog bite
Pasteurella multocida, Pasteurella canis, or Capnocytophaga canimorsus (potentially fatal in asplenic or immunosuppressed patients)
Cat bite
Pasteurella multocida >Streptococcal spp.
Human bite
Eikenella corrodens (a/w chronic infections), S. aureus (a/w severe infections), Peptostreptococcus, Enterococcus, and Bacteroides
Treatment: Bite-induced infections
Amoxicillin/clavulanate (treatment of choice)
Pathogenesis: Lyme disease
Ixodes tick feeds on infected animal reservoir → spirochetes stored in tick’s salivary glands → tick bites human and releases Borrelia spirochetes into dermis → erythema migrans develops at bite site 1 to 2 weeks later → if untreated, hematogenous dissemination + systemic symptoms
Three clinical stages of Lyme disease
- Early localized
- Early disseminated
- Chronic
Initial cutaneous manifestation; develops 7 to 14 days posttick attachment; p/w expanding annular plaque w/ central clearing (“bull’s eye” appearance) → reaches >5 cm diameter; favors trunk (#1 site in children), legs (#1 site in adults), and intertriginous areas; lesion self-resolves in 4 weeks if untreated
Erythema migrant
Multiple smaller annular lesions; arise days to weeks after primary erythema migrans lesion
Disseminated erythema migrans
Strongly a/w B. afzelii and B. garinii; p/w firm, plum-colored tender nodule/plaque on earlobes (children), or nipple/areola (adults)
Borrelial lymphocytoma
Strongly a/w B. afzelii and B. garinii; occurs months to years after initial infection; two clinical phases: erythematous plaques with “doughy”/swollen skin on distal extremities (early phase; easily treated/reversible) → progresses to atrophic “cigarette-paper” skin w/ telangiectasias (chronic phase; recalcitrant to treatment) and subcutaneous fibrous nodules overlying joints
Acrodermatitis chronica atrophicans
Treatment: Lyme disease
First line: doxycycline
In pregnancy or children <8 years old → amoxicillin is treatment of choice
T/F: Tick must be attached for >24 hours to transmit Lyme
True
Yaws
T. pallidum pertenue
Pinta
T. pallidum carateum
Endemic Syphilis/“Bejel”
T. pallidum endemicum
1° stage: legs most commonly affected; p/w indurated, red, painless papule that enlarges to 1–5 cm, then ulcerates (“Mother”); occurs at site of inoculation; may have hypomelanotic macules on dorsal wrists/hands
2° stage: multiple smaller widespread “daughter”
3° stage: necrotic and ulcerative abscesses that heal with severe/deforming scars + bony damage
Yaws
Skin-only disease
1° stage: legs most commonly affected; p/w papules surrounded by red halo; enlarges over months up to 12 cm
2° stage: smaller scaly papules and psoriasiform plaques erupt (“pintids”) and change in color from red → blue → brown → gray/black
3° stage: symmetric vitiligo-like lesions over bony prominences w/atrophic epidermis. Histology shows lichenoid interface + complete loss of melanocytes + epidermal atrophy
Pinta
1° stage: rarely noticed; p/w inconspicuous papule or ulcer in mouth or on nipples of breastfeeding women; may have hypomelanotic macules on extremities, genitalia, areolae, and trunk
2° stage: mucous membrane lesions (mucosal patches, condyloma lata, and angular stomatitis) + generalized lymphadenopathy +/− skin lesions
3° stage: Gumma formation of mucous membranes, skin, and bones
Endemic Syphilis/“Bejel”
Treatment: Nonvenereal (endemic) treponematoses
Benzathine PCN
Early congenital (<2 years old) syphilis
Snuffles Dactylitis Parrot’s pseudoparalysis Epiphysitis Hepatitis
Late congenital (>2 years old) syphilis
keratitis, mulberry molars, Hutchinson’s teeth (notched/peg-shaped incisors), rhagades (linear scars at angles of mouth) saddle nose, Higoumenakis syndrome, Clutton’s joints, optic atrophy, corneal opacities, and eighth nerve deafness
Incubation: Primary chancre
10-90 days
Painless, well-defined, and indurated ulcer) w/ enlarged lymph nodes
Primary syphilis
Prodromal signs (e.g., malaise, fever, lymph node enlargement, and arthralgia)
Papulosquamous/maculopapular generalized rash (“copper colored”) w/ papules/plaques on palms/soles
“Moth eaten” alopecia
Split papules (syphilitic perlèche)
Mucous patches in oropharynx (condyloma lata-like lesions of the mouth)
Hypopigmented macules on neck (“necklace of Venus”)
Condyloma lata
Secondary syphilis
Gummas (skin, bones, liver, and organs) Cardiovascular syphilis (e.g. aortitis) Neurosyphilis (e.g., paresis, meningitis, ataxia, tabes dorsalis, optic atrophy, gummas, and Argyll-Robertson pupil (accommodates to light, but does not react)
Tertiary syphilis
Treatment: Syphilis
IM benzathine PCN (2.4M IU ×1 dose for primary/secondary/early latent disease; 7.2M IU total for late latent disease)
Most sensitive and specific tests for Syphilis
FTA-ABS and MHA-TP
First serologic test to become positive for Syphilis (within 1-2 weeks)
RPR and VDRL
Used to monitor response to therapy as titers decrease and then become negative after successful treatment
RPR and VDRL
Stain identifies spirochetes
Warthin-Starry
Overall most sensitive and specific test for diagnosis of primary syphilis
Positive darkfield examination
Histology: slender, elongated psoriasiform epidermal hyperplasia + lichenoid interface changes + “dirty” dermal inflammatory infiltrate (neutrophils, cell debris, and abundant plasma cells)
Secondary syphilis
Chancroid
Hemophilus ducreyi (Gram(-) coccobacilli)
Painful, purulent ulcers with ragged/undermined borders and fibrinous base (may get ’kissing ulcers’ from apposition of skin with initial ulcer)
Prepuce/coronal sulcus/frenulum are common sites
Painful inguinal lymphadenitis (40%)
Chancroid
Treatment: Chancroid
Azithromycin 1 gm PO × 1 dose
Gonorrhea
Neisseria gonorrhoeae (Gram (-) diplococci)
Most findings are not cutaneous, but can get hemorrhagic acral pustules w/arthritis (of larger joints), and fever (arthritis-dermatosis syndrome) if hematogenous dissemination occurs
Gonorrhea
Treatment: Gonorrhea
Dual therapy: Ceftriaxone 250 mg IM ×1 dose + Azithromycin 1 gm PO × 1 dose
Lymphogranuloma venereum
Chlamydia trachomatis (serotypes L1–3)
Stage 1 (after 3–12d incubation period): painless ulcer which resolves (transient) +/− lymphangitis Stage 2 (10–30 days, up to 6 months after stage 1): buboes (unilateral, painful, erythematous, and enlarged inguinal lymph nodes) w/ ’groove sign’ (enlarged nodes above and below Poupart ligament); buboes may rupture → pus drainage and sinus tracts Stage 3 (months-years after stage 2; aka ano-genito-rectal syndrome): proctocolitis w/ perirectal abscesses, fistulas, strictures/stenoses, and ’lymphorrhoids’ (perirectal/intestinal lymphatic hyperplasia)
Lymphogranuloma venereum
Treatment: Lymphogranuloma venereum
Doxycycline 100 mg PO BID × 21 days
Granuloma inguinale
Klebsiella granulomatis (Gram-negative bacillus)
Enlarging chronic painless ulcer with ’beefy red,’ friable, hypertrophic granulation tissue (avg incubation = 17 days)
Get ’pseudobuboes’ (nodules), genital swelling, and secondary infections (→ bad odor)
Most common sites: prepuce/glans/frenulum/coronal sulcus (men); vulvar area (women)
May get extragenital lesions as a result of dissemination or autoinoculation (skin, bones, oral, and abdominal)
Granuloma inguinale
Treatment: Granuloma inguinale
Azithromycin 1 gm PO once weekly (or 500 mg daily) for at least 3 weeks AND until all lesions have resolved
Safety pin’ Donovan bodies on Wright or Giemsa stain of smears
Granuloma inguinale
’Gamma-Favre bodies’ in macrophages on Giemsa stain
Lymphogranuloma venereum
Culture for Neisseria gonnorheae
Thayer-Martin media
‘School of fish’ sign on Giemsa stain of exudate smear
Chancre
Acid-fast, alcohol-fast, aerobic bacillus, and ↑risk in HIV
Mycobacterium tuberculosis
Test better for patients who have had BCG (live, attenuated M. bovis) vaccination (false (+) with skin test)
Interferon-γ release assays (QuantiFERON® Gold)
In patients w/o previous infection (hence no immunity against TB); 2 to 4 week inoculation period; painless, red, and indurated papule that ulcerates – heals after 3 to 12 months; may spread to lymph nodes
Tuberculous chancre
Reinfection via inoculation, in patients w/ previous infection w/ moderate-to-high immunity; #1 form of cutaneous TB; warty/verrucous, growing papule may heal over years
Tuberculosis verruca cutis
Contiguous spread or hematogenous/lymphatic; red-brown, sometimes annular, papules/plaques (with “apple jelly” color on diascopy) that → scarring centrally; head/neck #1 site; moderate-to-high immunity
Lupus vulgaris
Result of contiguous spread of infection to skin from underlying disease (usually cervical lymph nodes and bones); fluctuant nodules that develop sinus tracts, draining to skin, with tethered appearance; low immunity
Scrofuloderma
Patients with advanced TB and poor cell-mediated immunity; autoinoculation of mucosa/skin close to anatomic orifice draining active systemic TB infection → ulceration/drainage
Orificial tuberculosis
Hematogenous dissemination from lung, most often in immunosuppressed pts; pinpoint blue-red crusty papules → small scars
Acute miliary tuberculosis
Hematogenous dissemination → deep nodule that ulcerates/drains; immunosuppressed pts
Tuberculous gumma
Obligate intracellular, weakly acid-fast bacillus that parasitizes macrophages and Schwann cells which requires cool temperatures (30°C–35°C) for growth → predilection for cooler areas of skin (nose, testes, and ear lobes) and peripheral nerves that lie close to skin surface;
transmitted primarily by nasal/oral droplets; also 9-banded armadillos in the southeast United States; cannot be cultured in vitro → must be cultivated in mouse footpads or in armadillos
Mycobacterium leprae
Chronic, deforming disease characterized by skin and nerve involvement; characterized by granulomas and neurotropism, both within skin and peripheral nerves
Leprosy (Hansen’s disease)
Incubation period of Leprosy (Hansen’s disease)
Average 4–10 years, but up to 30 years
T/F: Peripheral nerves are enlarged in all forms
False
except Indeterminate
Earliest stage of leprosy p/w solitary, ill-defined hypopigmented macule, without enlargement of peripheral nerves; disease will either self-resolve, or evolve into one of five leprosy forms (LL, BL, BB, BT, or TT)
Indeterminate leprosy
Result of change in cell-mediated (Th1) immunity against M. leprae. May either be downgrading (borderline leprosy pt who “downgrades” toward lepromatous pole) or upgrading (increase in cell-mediated immunity). Both may p/w ulceration of existing lesions and preferential targeting of nerves, resulting in dangerous neuritis (= emergency!); generally lacks systemic symptoms; highest risk with Borderline forms (BL > BB, BT); Treatment = prednisone
Type 1 (reversal reaction)
Th2 (humoral)-mediated formation of immune complexes, resulting in multisystem vasculitis and EN-like lesions scattered at previously unaffected skin sites (medial thighs and extensor forearms are #1 sites); prominent systemic symptoms; highest risk with LL and BL forms; Treatment = thalidomide
Type 2 (erythema nodosum leprosum)
Severe necrotizing vasculitis w/ thrombosis; only occurs in patients from western Mexico with diffuse lepromatous leprosy; p/w purpuric macules and ulcerative bullous lesions below the knees; Treatment = prednisone
Lucio phenomenon
Histology: Grenz zone, diffuse infiltrate of parasitized foamy histiocytes (Virchow cells), free-floating clumps of bacilli (globi) in dermis, and “onion-skin” pattern around nerves; lacks well-formed granulomas
Lepromatous Leprosy (LL)
Histology: Well-formed sarcoidal granulomas w/linear arrangement (East-West) along nerves, numerous Langhans giant cells, fragmented nerve fibers, lacks organisms (no globi or Virchow cells), and Grenz zone
Tuberculoid (TT) Leprosy
Small hypopigmented macules, papulonodules, and diffuse infiltration (→ leonine facies, elongated earlobes, and madarosis)
Lepromatous Leprosy (LL)
Plaques and dome-shaped lesions
Borderline Leprosy
Dry, scaly, hypopigmented, and anesthetic plaques with raised peripheral rim and central atrophy +/− alopecia and anhidrosis
Tuberculoid (TT) Leprosy
Highest risk for type 1 reactions
Borderline Leprosy
High risk for type 2 reaction
Lesions do not have anhidrosis or alopecia
Lepromatous Leprosy (LL)
Treatment (WHO recommendations): Multibacillary
rifampicin 600 mg Qmonth + dapsone 100 mg QD + clofazimine 300 mg once a month and 50 mg daily
12 months
Treatment (WHO recommendations): Paucibacillary
rifampicin: 600 mg Qmonth + dapsone 100 mg QD
6 months
More commonly seen in AIDS patients; found in environment (water, soil, and animals); pulmonary infection is most common finding; skin findings w/ primary inoculation or via dissemination (pustules, ulcers on legs, and nodules); ↑alkaline phosphatase; clarithromycin/azithromycin + ethambutol +/− rifampin
Mycobacterium avium complex
Acquired via cutaneous contact (usually hands w/ abrasions) with aquatic environments (e.g., fish tanks and swimming pools) → erythematous/blue ulcerating nodules in a sporotrichoid pattern; Diagnosis is confirmed with culture: grows best at 31 degrees Celsius (~3 weeks required for growth), as opposed to the usual 37 degrees for most other mycobacteria;
Treatment: clarithromycin +/− rifampin/ethambutol, minocycline, and TMP-SMX
Mycobacterium marinum
Usually in Africa, in areas close to water bodies; nodule → ulcer on extremities; can become >15 cm and extend to bones; tx: excision (treatment of choice), local heating, rifampin + streptomycin, and amputation
Mycobacterium ulcerans aka Buruli ulcer
Rapid growing mycobacteria; saprophytic organisms; can get infections posttrauma/surgery or medical treatments (e.g., implant placement, liposuction, and botulinum toxin)/tattoo/nail salon footbaths; skin presentations vary, but most common is inflamed subcutaneous nodules in sporotrichoid pattern; clarithromycin is treatment of choice, but surgical treatment may be needed
Mycobacterium fortuitum, chelonae, and abscessus
Tinea capitis
Trichophyton tonsurans (#1 cause in United States), Microsporum canis (#1 cause worldwide; more inflammatory), and T. violaceum (East Africa)
Endothrix (black dot; arthroconidia within hair shaft)
T. rubrum, T. tonsurans, T. schoenleinii, T. yaounde, T. violaceum, T. gourvilli, and T. soudanense (Mnemonic: “Ringo Gave Yoko Two Squeaky Violins”)
Ectothrix (arthrospores around hair shaft)
Fluorescent (via Wood lamp – pteridine): M. canis, M. audouinii (formerly #1 cause in children), M. gypseum, M. ferrugineum, M. distortum, and T. schoenleinii (Mnemonic: “Cats And Dogs Fight and Growl Sometimes”)
Nonfluorescent: T. mentagrophytes, T. rubrum, M. nanum, T. megninii, T. gypseum, and T. verrucosum
Favus
T. schoenleinii > M. gypseum, T. violaceum
Kerion
M. canis, T. verrucosum, T. mentagrophytes, and T. tonsurans
Majocchi granuloma
T. rubrum most common
Tinea corporis
T. rubrum most common
Tinea imbricatum
T. concentricum
Tinea barbae
T. verrucosum, T. mentagrophytes, T. tonsurans, and T. rubrum
Tinea faceii
Usually zoophilic species (M. canis and T. metagrophytes) > T. rubrum; most commonly in kids after visiting rural areas
Tinea cruris
T. rubrum >E.floccosum and T.interdigitale
Moccasin and interdigital Tinea pedis
T. rubrum > E. floccosum (mocassin), T.interdigitale (interdigital)
Vesicular/bullous Tinea pedis
T. mentagrophytes
Distal subungual onychomycosis
T. rubrum, T.interdigitale, and E. floccosum
Proximal white subungual onychomycosis
T. rubrum
↑risk in HIV
White superficial onychomycosis
T. mentagrophytes (adults) vs T. rubrum (children)
Restricted to humans and cause a chronic, mild inflammatory response; includes all Trichophyton spp. (except T.mentagrophytes and T.verrucosum), E.floccosum, M.audouinii, and M.ferrugineum
Anthropophilic
Primarily affect animals; cause massive inflammatory response in humans; includes M.canis (cats and dogs), M.nanum (pigs), T.verrucosum (cattle), and T.mentagrophytes (rodents)
Zoophilic
Found in soil; cause severe inflammatory response and scarring in humans; M.gypseum (soil) is the only common species in this class
Geophilic
Histology - Dermatophytes
septate hyphae in stratum corneum or nail plate, brisk dermal inflammation (vs minimal in tinea versicolor) +/− neutrophilic microabscesses in epidermis or corneum/nail plate
PAS (red) and GMS (black)
Chlorazol black E
Chitin stain – hyphae will be green
Calcofluor white
Chitin stain – blue or green with fluorescence microscopy
Pathogenesis - Dermatophytes
virulence factors (hydrolases and keratinases) allow penetration into stratum corneum and the released enzymes induce inflammation (Th1 response)
Yellow cup-shaped crusts (scutula) that cluster together, resulting in a honeycomb appearance and can → scarring
Favus
Boggy inflamed nodule/abscess with pustules and possible lymphadenopathy which may → scarring
Kerion
Concentric and polycyclic rings of scale
Tinea imbricatum
Erythematous papules/nodules around hair follicles, particularly lower legs (may arise from tinea pedis); systemic antifungals needed for treatment
Majocchi’s granuloma
Erythematous follicular-based papules, often in an annular distribution most common in kids; treat with systemic antifungals
Tinea faciei
Histology: hyphae and spores (“spaghetti and meatballs”) seen in stratum corneum (also on KOH)
Pityriasis versicolor
Hyper- or hypopigmented finely scaling circular/oval macules/patches in sebaceous distribution (scalp, face, neck, upper chest, and upper back); more common in darker skin/adolescents/summer
Pityriasis versicolor
Pathogenesis: Pityriasis versicolor
Overgrowth of normal flora, which is ubiquitous (esp. with warmth and humidity in the right host); hypopigmentation due to melanocyte inhibition by azelaic acid (dicarboxylic acid byproduct of Malassezia)
Treatment: Pityriasis versicolor
Topical or systemic azole-antifungals, selenium sulfide shampoo, or topical ciclopirox
Black Piedra
Piedra hortae
White Piedra
Trichosporon asahii (most strongly linked to white piedra; formerly, T. beigelii; may cause disseminated disease in immunocompromised pts), T. ovoides, T. inkin, and T. cutaneum
Microscopy: Piedra
Black or white concretions along hair (encircle hairs, unlike the sac-like appearance of lice)
White piedra with soft mobile nodules; black piedra with hard nonmobile nodules
Treatment: Piedra
Hair shaving/cutting and antifungal shampoos; systemic antifungals if recalcitrant
Tinea nigra
Hortaea werneckii
Microscopy: Tinea nigra
Dark brown septate hyphae with budding yeast in thickened stratum corneum
Dark-brown/black macule or small patch on palms/soles, limited to stratum corneum
Tinea nigra
Treatment: Tinea nigra
Azole creams, Whitfield’s ointment; oral terbinafine if recalcitrant
Sporothricosis
Sporothrix schenckii (ubiquitous saprophyte; endemic to Central/South America and Africa)
Microscopy: Sporothricosis
usually not well-visualized with stains; granulomatous inflammation with plasma cells and asteroid corpuscles (Splendore-Hoeppli phenomenon); organisms are cigar-shaped budding yeast
Pathogenesis: Sporothricosis
Traumatic inoculation from soil via plant thorns, wood splinters, and sphagnum moss ≫ cats/rodents/armadillo bites; inhalation of spores
Multiple ascending ulcerated nodules or subcutaneous abscesses, most frequently in gardeners, agriculture/farm workers, and veterinarians; may lead to erythema nodosum
Sporothricosis
Treatment: Sporothricosis
Obtain fungal culture (difficult to find in tissue samples), itraconazole (treatment of choice), SSKI, and amphotericin B in disseminated disease
Lobomycosis
Lacazia (Loboa loboi) - infects freshwater dolphins in South American Rivers
Keloid-like verrucous fibrotic nodules that can ulcerate; men ≫ women; rural areas
Lobomycosis
Microscopy: thick-walled yeast with tubular connections between cells – “pop bead” or “chain of coins” appearance
Lobomycosis
Madurella spp. Pseudallescheria boydii (most common), Exophiala jeanselmei, and Acremonium spp.
Eumycetoma (fungus)
Nocardia (N. brasiliensis [#1 bacterial cause] and N. asteroides both have white grains), Actinomadura spp. (A. pelletieri = red grains; A. madurae = cream or pink grains), and Streptomyces somaliensis (yellow-brown grains)
Actinomycetoma (bacteria)
Slow progression of tumors with sinus tracts draining grains, which are fungal or bacterial aggregates; most common on feet/lower legs; long-standing lesions → bone and visceral involvement
Mycetoma
Treatment: Mycetoma
Actinomycetoma: sulfonamides and other antibacterial agents
Eumycetoma: surgical debridement and several month courses of azole antifungals
Chromoblastomycosis
Fonsecaea pedrosoi
Microscopy: pseudoepitheliomatous hyperplasia, granulomatous dermal inflammation with medlar bodies (pigmented muriform cells, “copper pennies”)
Chromoblastomycosis
Weeks to months after inoculation, pruritic papules/nodules that expand and become verrucous with black dots; does not invade muscle or bone; chronic lesions can → SCC
Chromoblastomycosis
Pathogenesis: Chromoblastomycosis
Traumatic inoculation by thorns or splinters
Histoplasmosis
Histoplasma capsulatum var. capsulatum
Ohio and Mississippi River valley
Microscopy: tuberculoid granuloma with intracellular 2–4 μm yeast in histiocytes (looks like leishmaniasis, but see yeast have surrounding halo and are more evenly distributed throughout histiocyte cytoplasm; lacks “marquee sign” and kinetoplast)
Histoplasmosis
Pathogenesis: Histoplasmosis
Inhalation (esp. bird and bat feces) with hematogenous spread (can go to liver, spleen, bone marrow, and brain; skin involvement more common in HIV, often p/w umbilicated or “molluscoid” papules)
Primary cutaneous chancre with lymphangitis and lymphadenitis (rare); more commonly, secondary cutaneous molluscoid nodules, cellulitis, ulcers, panniculitis, and oral lesions
Pulmonary manifestations = most common presentation
Histoplasmosis
Treatment: Histoplasmosis
Itraconazole (mild-moderate disease), or amphotericin B (severe disease)
Blastomycosis
Blastomyces dermatitidis
Eastern United States Great Lakes, Ohio, and Mississippi River valleys
Microscopy: pseudoepitheliomatous hyperplasia, granulomatous dermal inflammation with unipolar budding yeast (8–18 µm) (broad-based buds)
Blastomycosis
Pathogenesis: Blastomycosis
Inhalation with subsequent hematogenous spread to skin (>75% of cases), bones, and genitourinary tract (e.g., prostate, spleen, liver, and brain)
Primary cutaneous form (rare) presents with lymphangitis and lymphadenitis at injury site
Secondary cutaneous form (more common; due to hematogenous dissemination from lungs to skin), presents with verrucous nodules, abscesses, and ulcers (can occur orally as well)
Pulmonary manifestations = most common presentation
Blastomycosis
Treatment: Blastomycosis
Polyene and azole antifungals (mainly itraconazole) and amphotericin B (severe disease)
Coccidioidomycosis
Coccidioides immitis
Desert Southwest United States, Mexico, and Central/South America
Microscopy: large (up to 100 µm) spherules containing endospores; also has PEH and granulomatous inflammation
Coccidioidomycosis
Pathogenesis: Coccidioidomycosis
Inhalation with hematogenous spread to skin (as well as CNS and bone); very rarely primary cutaneous infection
Verrucous nodules/papules, pustules, abscesses, or ulcerative lesions
Pulmonary manifestations = most common presentation
Coccidioidomycosis
Treatment: Coccidioidomycosis
Limited and cutaneous: itraconazole
Severe: amphotericin B
Meningeal: amphotericin B and fluconazole
Paracoccidioidomycosis
Paracoccidioides brasiliensis
Southern United States, Mexico, and Central/South America
Microscopy: Pseudoepitheliomatous hyperplasia, granulomatous dermal inflammation with multipolar budding yeast (mariner’s wheel)
Paracoccidioidomycosis
Pathogenesis: Paracoccidioidomycosis
Inhalation of infected soil (can disseminate to skin, liver, adrenal glands, lymph nodes, gastrointestinal tract, and spleen); rarely may arise from direct inoculation in skin
Granulomatous ulcerative oropharyngeal and perioral involvement in 70% of adults; cutaneous lesions can be contiguous, hematogenous, or via inoculation; clinical appearance of ulcers with infiltrated borders and hemorrhagic dots, and associated lymphadenopathy (can be massive) Men >>> women Pulmonary disease (granulomatous and chronic) most common presentation
Paracoccidioidomycosis
Treatment: Paracoccidioidomycosis
Mild: TMP/SMX
Moderate: itraconazole
Meningeal: fluconazole or voriconazole
Severe: amphotericin B
Microscopy: KOH = yeast and pseudohyphae
Candidiasis
Pathogenesis: Candidiasis
Candida species form biofilm on plastic medical devices
SAPs (secretory aspartyl proteinases) and phospholipases aid in fungal adhesion and tissue invasion
Chitin, mannoprotein and glucan may function as adhesins, which allow candida to adhere to mucosal surfaces
C. albicans exists in normal flora of skin and digestive/genitourinary tracts with pathologic state with immunosuppression, and debilitation and imbalances in microbiome
Usually starts in GI tract; 10% of bloodstream infections; 30% mortality in systemic candidiasis despite antifungal therapy usually in immunosuppressed patients who are neutropenic; scattered papules/nodules, occ. hemorrhagic and ecthyma gangrenosum-like; also infect muscles, retina, internal organs, and heart valves
Deep-seated candidiasis
Third web space of fingers; also 4th web space of toes
Erosio interdigitalis blastomycetica
Central smooth erythema of tongue
Median rhomboid glossitis
Typically see beefy red color + satellite pustules +/− erosions
Candidal intertrigo
Perlèche; RFs: edentulous, elderly, atopic dermatitis, and vitamin deficiencies
Angular cheilitis
Treatment: Candidiasis
Mucocutaneous: polyenes (e.g., Nystatin) and azole preparations (e.g., clotrimazole and fluconazole)
Systemic: amphotericin B, azoles, and echinocandins
Cryptococcosis
C. neoformans and C. gattii
(In bird droppings particularly pigeons and bark/fruit of tropical trees; C. neoformans – ubiquitous, C. gattii – tropical, subtropical)
Microscopy: single-celled sphere with a double cell wall and thick capsule (“halo” appearance), may have one or more buds (blastoconidia); collections of organisms look like soap bubbles
Cryptococcosis
Stains: India ink, PAS, mucicarmine, GMS, and Fontana-Masson
Pathogenesis: Cryptococcosis
Inhalation → lungs (1° pulmonary infection, usually mild) → hematogenous spread (CNS, bones, and skin); can also arise from primary inoculation of skin (rare)
More common in immunosuppressed individuals (esp. in HIV/AIDS, but also associated with sarcoidosis and pregnancy)
Glucuronoxylomannan polysaccharide capsule is a virulence factor
Papules/nodules (often molluscum-like) that can be umbilicated and/or ulcerated, and prefer head/ neck, mouth, and nose
Patients with 2° cutaneous lesions have high mortality rate
Nodular lymphangitic syndrome – nodule at inoculation site, nodular lymphangitis, and adenopathy
Meningoencephalitis is a serious and common manifestation
Cryptococcosis
Treatment: Cryptococcosis
Mild: oral fluconazole
CNS: amphotericin B and flucytosine
Aspergillosis
Aspergillus fumigatus (most common)
Microscopy: septate hyphae with 45° angle branching
Aspergillosis
Pathogenesis: Aspergillosis
Can be 1° cutaneous disease (most commonly A. flavus) via direct inoculation (e.g., IV catheter, trauma sites, burn sites, and disturbed skin under dressings) vs 2° cutaneous disease (most commonly A. fumigatus; more common, typically in immunosuppressed, esp. neutropenic) via inhalation → pulmonary aspergillosis → disseminated disease
Both can → hematogenous spread with a tendency for vascular invasion causing thrombus and necrosis
Six clinical forms including erythematous edematous plaques, nodules with necrotic centers, hemorrhagic bullae, and necrotic ulcers
Can involve CNS, heart, kidneys, bone, and GI tract
Aspergillosis
Treatment: Aspergillosis
Azoles, echinocandins, and amphotericin B
Fusarium
Fusarium solani most common
Microscopy: 45° angle branching, similar to Aspergillus
Fusarium
Pathogenesis: Fusarium
More common in immunosuppressed; severe burns (most common fungus cultured in burn patients); cutaneous disease via direct inoculation and hematogenous spread with a tendency for vascular invasion causing thrombus/necrosis
Erythematous; edematous plaques more common than subcutaneous nodules (purpuric or ecthyma gangrenosum-like); panniculitis
Fusarium
Penicilliosis
Penicillium marneffei
Southeast Asia
Zygomycosis (mucormycosis)
Order Mucorales, genera Rhizopus, Rhizomucor, Mucor, Absidia, and others – systemic and cutaneous disease
Microscopy: broad ribbon-like nonseptate hyphae with 90° angle branching, angioinvasive with thrombosis
Zygomycosis (mucormycosis)
Pathogenesis: Zygomycosis (mucormycosis)
Most commonly enter via respiratory tract (though there are other portals of entry like skin), and can invade blood vessels → thrombosis/infarction/ necrosis
More common in immunosuppressed patients, but also nonimmunodeficient (e.g., severe diabetes and severe burns)
Forms: rhinocerebral pulmonary, gastrointestinal, primary cutaneous, and disseminated All forms are rapidly progressing and commonly fatal Cutaneous lesions (can be primary or secondary) typically indurated, necrotic black plaques/eschars most commonly seen on face (nasal and oral in rhinocerebral type); from surgery, catheterization, or burns Rhinocerebral type most common, usually in diabetes patients with DKA, may have epistaxis, facial pain, periorbital cellulitis, proptosis, and loss of extraocular muscle movement (2° to cranial nerve palsies)
Zygomycosis (mucormycosis)
Treatment: Zygomycosis (mucormycosis)
Aggressive surgical resection of all necrotic areas (crucial to survival of patient) and amphotericin B (lipid formulation); posaconazole may be alternative
Due to dematiaceous (pigmented) fungi: Exophiala jeanselmei (#1 cause), Wangiella dermatitidis, Alternaria, bipolaris, Phialophora, and Curvularia
Phaeohyphomycosis
Subcutaneous, possibly draining, inflammatory abscesses/cysts (may mimic Baker cysts)
Microscopy: cyst composed of macrophages and short hyphae, with a fibrous capsule
Hyphae are pigmented/brown, and stain (+) with Fontana-Masson
Phaeohyphomycosis
Slow-growing friable, red-purple, soft, lobulated, mucosal polyps, particularly on nose (associated with epistaxis), and conjunctivae; young men most commonly
Microscopy: Very large (up to 300 µm sporangia containing trophozoites in dermis
Rhinosporidiosis
Rhinosporidium seeberi
Nodules/ulcers/plaques and/or olecranon bursitis introduced into skin via trauma in contaminated water
Microscopy: organisms have a morula-like appearance on H&E
Protothecosis
Prototheca wickerhamii
Most consistent factor associated with scabies
Overcrowding
Scabies
Sarcoptes scabies var. hominis
Most common complication of Scabies
Secondary bacterial infections
Scabies in immunosuppressed patients
Crusted (Norwegian) scabies
Host-species restricted with 30-day life-cycle within stratum corneum; 1 week survival off human; classically affects interdigital webspaces, wrists, genitals (a/w chronic, reactive inflammatory nodules), and trunk; mineral oil scraping demonstrates scabies mite
Scabies
Treatment of choice: Scabies
Permethrin 5% cream
Head louse
Pediculus humanus capitis
Body louse
Pediculus humanus corporis
Pubic louse
Pthirus pubis
Active infection only if within 5 mm from scalp; most commonly located in occipital and postauricular areas
Mites can survive 36 hours w/o blood meal; nits are strongly adherent to hair shaft and can survive 10 days w/o blood meal
Head louse
Larger, but similar shape to head louse
Vector in epidemic typhus (R. prowazekii), louseborne relapsing fever (B. recurrentis), and trench fever (B. quintana)
Live and lay eggs on clothing; more common in homeless population (since unable to change/wash clothes regularly)
Body louse
Identify by four frontal crab-like appendages and short/broad body Maculae ceruleae (blue-gray macules due to bites) may be seen on surrounding skin
Pubic louse
Female burrows head-first into skin (usually feet/toes) and extrudes eggs from punctum before dying and being sloughed with epidermis; can → gangrene
Tungiasis
Burrowing flea – Tunga penetrans
Larvae cannot penetrate intact skin; once laid within open wound, penetrate subcutaneous structures and can continue to penetrate through cartilage and bone (leading to cranial penetration if developing near nose)
Wound myiasis
Chronic infection due to obligate intracellular protozoan
Exist in 2 forms: promastigote and amastigote
Vector: Sandflies (Phlebotomus or Lutzomyia)
Reservoirs: mainly canines and rodents
Leishmaniasis
Pathogenesis: Leishmaniasis
Within gut of sandfly, organisms proliferate into flagellated promastigotes → migrate to sandfly proboscis → sandfly bites human and transfers promastigotes → histiocytes engulf promastigotes, which then transform into amastigotes and multiply → develop clinical manifestations within weeks (cutaneous leishmaniasis) or many months-years later (mucocutaneous and visceral leishmaniasis)
Old world Leishmaniasis
L. major, L. tropica > L. aethiopica, L. infantum, and others
Vector: Phlebotomus sand flies
New world Leishmaniasis
L. mexicana, L. braziliensis, L. amazonensis, and others
Vector: Lutzomyia sand flies (also the vector of B. bacilliformis → verruga peruana, Carrion disease, bartonellosis, Oroya fever
Most common agents: L. major, L. tropica (>L. infantum)
Begins as a solitary, small, erythematous edematous nodule at bite site (usually exposed skin sites—arms, face, legs) that ulcerates or becomes verrucous (Fig. 5-20) → may later develop sporotrichoid spread with satellite lymphatic nodules and lymphangitis → heals with scarring over months to years
Old world cutaneous Leishmaniasis
Most common agents: L. mexicana (> L. braziliensis)
More varied presentation: ulcerations (Chiclero ulcer = ear lesion in workers who harvest chicle gum in forest), impetigo-like, lichenoid, sarcoid-like, nodular, vegetating, and miliary
New world cutaneous Leishmaniasis
More widespread cutaneous lesions; usually arises in immunosuppressed pts
Most common agent: L. amazonensis (Americas), L. aethiopica (Africa)
Multiple keloidal lesions of face (esp. nose) and extremities
Diffuse Cutaneous Leishmaniasis
Affects skin and mucous membranes; almost always in New World; Predominantly New world subspecies: L. braziliensis (> L. amazonensis, L. panamensis, and L. guyanensis); Present with lip, nose and oropharyngeal infiltration and ulceration; Progressive nasopharyngeal destruction → airway obstruction, mutilation of mouth and perforation of nasal septum (aka “tapir face” or espundia)
Mucocutaneous Leishmaniasis
Most severe form; due to systemic infection of bone marrow liver, spleen; Old World > New World; long incubation time months-years
Most common agents: L. donovani (India, Sudan, Bangladesh; most common cause in adults), L. infantum (Europe; often a/w HIV), L. chagasi
Present with fever, weight loss, diarrhea, abdominal tenderness, lymphadenopathy, hepatosplenomegaly, nephritis, intestinal hemorrhage, and death within 2 years (if not treated)
Skin changes: Specific: papules, ulcers at bite site; Non-specific: purpura, hyperpigmentation, kwashiorkor changes (brittle hair)
Visceral (Kala-azar, “black fever”)
New-onset cutaneous leishmaniasis lesions that arise up to 20 years after presumed recovery from untreated visceral leishmaniasis
Post-kala-azar dermal leishmaniasis
Culture: Leishmaniasis
Novy-McNeal-Nicolle medium
Histology: amastigotes with kinetoplasts are arrayed around periphery of parasitized histiocyte cytoplasm (“Marquee sign”); organisms are best seen on Giemsa
Leishmaniasis
Most sensitive and specific test for Leishmaniasis
PCR
Treatment: Cutaneous and mucocutaneous leishmaniasis
Pentavalent antimony (ToC)
Treatment: Visceral leishmaniasis
Amphotericin B (ToC)
African trypanosomiasis (sleeping sickness)
T. brucei gambiense (West Africa)/T. brucei rhodesiense (East Africa)
Vector: African trypanosomiasis (sleeping sickness)
Tsetse fly (Glossina)
Earliest sign: local pruritic inflammatory reaction at site of inoculation [48 hours]) → local lymphadenopathy and ulcerates → eschar with fever, headache, and joint pain at irregular intervals
Winterbottom’s sign (posterior cervical LAD) (2 to 3 weeks) → trypanids (erythematous, urticarial or macular diffuse eruptions [6 to 8 weeks]) → neurologic changes and Kerandel’s deep delayed hyperesthesia, daytime sleepiness (late stage)
African trypanosomiasis
Treatment: African trypanosomiasis
suramin or pentamidine (early)
melarsoprol, or eflornithine (CNS involvement)
American trypanosomiasis (Chagas disease)
T. cruzi
Vector: American trypanosomiasis (Chagas disease)
Triatomine bug (Reduviidae) Central/South America
Clinical presentation: local inflammatory lesion (often on face) at site of entry (Chagoma) → Romanña’s sign (unilateral eyelid edema and conjunctivitis at site of inoculation) → rapid unilateral painless bipalpebral edema → late heart, esophagus, and intestinal enlargement (megacolon)
American trypanosomiasis (Chagas disease)
Treatment: American trypanosomiasis (Chagas disease)
benznidazole and nifurtimox
Toxoplasmosis
Toxoplasma gondii
Vector: intestinal parasite of cats, but also infects dogs and rabbits
Hemorrhagic or necrotic papules
Acquired cutaneous disease occurs in pregnant women and immunocompromised patients
Congenital disease (TORCH syndrome)
Toxoplasmosis
Most common tropical parasite dermatosis; found in animal feces
Species – Ancylostoma brasiliense (most common)
Cutaneous larva migrans
Erythematous serpiginous cutaneous eruption (usually on feet) as a result of larva penetrating intact epidermis, but unable to penetrate human basement membrane zone (therefore unable to cause systemic disease)
Moves 2–10 mm/hr
Cutaneous larva migrans
Treatment: Cutaneous larva migrans
Albendazole, ivermectin, topical/oral thiabendazole, and liquid nitrogen
Moves faster (5–10 cm/hr)
Strongyloides stercoralis
Often indurated serpiginous papule on buttocks/groin
If disseminated, may get periumbilical (thumbprint) purpura and petechiae on trunk/proximal extremities
Loeffler’s syndrome = chronic strongyloidiasis (affects lungs and GI tract; eosinophilia)
Caused by contact with contaminated soil (e.g., sitting on beach)
Larva currens
Onchocerciasis
Onchocerca volvulus
Vector: Onchocerciasis
Simulium fly (black fly; also vector for tularemia; has also been implicated in Fogo selvagem form of pemphigus; present near fast-flowing rivers)
Pruritic papules (can be acute, chronic, or lichenified) → leopard skin (depigmentation and atrophy); nodules (onchocercomas) over bony prominences; may develop Mazzotti reaction if given diethylcarbamazine Nodules of female microfilariae; male microfilariae migrate between nodules to mate
Onchocerciasis
Treatment: Onchocerciasis
Ivermectin (treatment of choice)
Newer trials with doxycycline (kills symbiotic Wolbachia bacteria); surgical excision of onchocercomas
Vector: Loa loa
Chrysops (Mango/deer flies; also transmit tularemia)
Calabar swellings (recurrent migratory focal angioedema on limbs); visible migration of adult worm across eyes
Loiasis
Treatment: Loiasis
Diethylcarbamazine
Filariasis
Brugia malayi/timori and Wuchereria bancrofti
Vector: Filariasis
multiple mosquito spp. of Culex (also West Nile virus vector), Aedes (also vector of chikungunya fever, Dengue fever, and yellow fever), and Anopheles (also vector of malaria and yellow fever) mosquitoes
Treatment: Filariasis
Diethylcarbamazine (ToC)
Species: Schistosoma, during the cercarial stage (snails are a vector)
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Northern United States and Canada fresh water
Clinical presentation: papules and papulovesicles on uncovered skin 10 to 15 hours post exposure, lasts 5 to 7 days
Swimmer’s itch (“cercarial dermatitis”)
Species: Edwardsiella lineata (sea anemone) and Linuche unguiculata (thimble jellyfish) during larval stage
Southern United States and Caribbean salt water
Clinical presentation: pruritic papules and wheals in covered areas within hours with new lesions for days
Seabather’s eruption
Nitrophorin is one of its salivary products responsible for human immune reaction; p/w grouped “breakfast, lunch and dinner” urticarial papules at bite sites
Bed bugs
Cimex lectularius
Direct contact with hairs and toxin-mediated reactions (not allergy)
Train-track appearance of urticaria or hemorrhage
Ophthalmia nodosa are ocular reactions as hairs tend to migrate inward
Lepidopterism
Overall the most effective insect repellant
DEET (N,N-diethyl-3-methylbenzamide)
Live in hair follicles of humans
Possible association with rosacea/perioral dermatitis
Demodex (Demodicidae)
Involved in indoor allergies in atopic patients
Dust mite (Dermatophagoides)
Has characteristic red hourglass on body
Acute pain and edema at site
Systemic symptoms: chills, abdominal pain/ rigidity, rhabdomyolysis, chest pain, sweating, hypertension, and shock
α-Lactotoxin depolarizes neurons
Black widow spider - Latrodectus mactans
Characteristic dark brown-black violin/fiddle shaped marking
Necrosis with eschar formation at site of bite (which is painless; erythema → ischemia → thrombosis)
Toxins: sphingomyelinase D and hyaluronidase (allows eschars to spread)
Brown recluse spider - Loxosceles reclusa
