Infectious Diseases




(1)
University of Florida, College of Medicine, Gainesville, FL, USA

(2)
Private Practice:, Orlando, FL, USA

 




4.1 Viral Infections



A. HUMAN HERPESVIRUSES (HHV)






  • Eight types of HHVs:



















HHV1 → HSV1

HHV5 → CMV

HHV2 → HSV2

HHV6

HHV3 → VZV

HHV7

HHV4 → EBV

HHV8 → KSHV


Herpes Simplex Virus 1 and 2 (HHV1, HHV2) (Figure 4.1A-C)





  • Neurotropic virus which hides in the dorsal root ganglion until reactivation


  • HSV-1 associated more with orolabial herpes, HSV-2 with genital herpes


  • Primary infections:



    • Primary herpetic gingivostomatitis: typically in children, abrupt onset with striking gingivitis (erythematous, friable gingiva), painful vesicles clustered on oral mucosa, tongue, lips and/or perioral skin → vesicles rupture, leaving small ulcers with characteristic gray base; ± pharyngitis, tonsillitis, difficult to eat and swallow, enlarged lymph nodes, fever, and anorexia


    • Primary genital infection: more severe and prolonged than recurrent infection, presents with constitutional symptoms and painful grouped vesicles in genitalia → progress to pustules, crusting and exquisitely tender ulcers, ± painful lymphadenopathy, cervicitis, urethritis, proctitis


  • Recurrent infections:



    • Herpes labialis: most common HSV-1 manifestation triggered by pyrexia, stress, sunburn, and/or trauma; prodrome (pain, burning, tingling) may precede eruption; grouped vesicles on erythematous base which typically evolve into pustules and then painful ulcers (often involving vermilion border)


    • Genital herpes: ± prodrome followed by grouped vesicles → pustules → ulceration


  • Other types of infections:



    • Herpes gladiatorum: HSV primary infection primarily noted in wrestlers and involving extramucosal sites typically over face, neck or arms


    • Herpetic whitlow: painful primary herpetic infection of hand (typically distal phalanx) resulting in exquisite pain and swelling of finger with characteristic vesicular lesions; more common in health care workers or caregivers


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Figure 4.1:
A: Recurrent HSV infection(Courtesy of Dr. Paul Getz)B: Primary genital HSV(Courtesy of Dr. Paul Getz)C: Primary genital HSV









    • Eczema herpeticum (Kaposi varicelliform eruption): rare disseminated form of HSV mainly seen with atopic dermatitis (also Darier disease, Hailey-Hailey, etc); presents as monomorphic umbilicated vesiculopustules or punched out ulcerations with hemorrhagic crust; may progress to life-threatening infection (Figure 4.2A)


    • Herpes-associated erythema multiforme (HAEM): self-limited eruption associated with HSV infection; presents with typical concentric target plaques; begins on extremities and spreads centripetally, ± mucosal involvement


    • HSV encephalitis: dormant HSV in trigeminal ganglion → travels retrograde to the brain, targets temporal region of brain, 70% mortality if untreated


    • HSV folliculitis: rare manifestation


    • Chronic ulcerative HSV: presents mainly in immunocompromised patients as persistent ulcers involving perianal/buttock area, can be pustular, exophytic, or verrucous as well (Figure 4.2B)


    • Keratoconjunctivitis: can be primary or recurrence, latter presents typically with branching dendritic corneal ulcerations (seen with fluorescein stain), can lead to scarring and blindness (Figure 4.2C)





  • Diagnosis:



    • Tzanck smear shows multinucleated epithelial giant cells (fusion of infected keratinocytes) – does not differentiate between HSV and VZV


    • Viral culture or direct fluorescent antibody (DFA)


    • Histology shows keratinocyte edema causing ballooning degeneration and acantholysis, intranuclear inclusion bodies and dense inflammatory infiltrate ± epidermal/adnexal necrosis


  • Treatment: acyclovir, valacyclovir, famciclovir; if acyclovir-resistant use foscarnet or cidofovir



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Figure 4.2:
A: Eczema herpeticum(Courtesy of Dr. Sophie M. Worobec)B: Perianal HSV ulcers(Reprint Bolognia JL, Jorizzo JL, Rapini RP. Dermatology. 2nd ed. St. Louis, MO: Mosby Elsevier; 2008.)C: HSV corneal ulcer(Reprint from Mandell G, ed. Atlas of Infectious Diseases. Philadelphia, PA: Current Medicine LLC; 2002.)


Varicella-Zoster-Virus (HHV3, VZV, Herpes Zoster) (Figure 4.3B-C)





  • Initial infection causes varicella (chickenpox, Fig 4.3A) and following resolution, virus lies dormant in spinal dorsal root ganglion until reactivation of latent virus causing localized cutaneous eruption (herpes zoster or shingles)


  • Presents with grouped, painful erythematous macules and papules along single sensory dermatome (rarely crossing midline) → vesicles/bullae → rupture forming hemorrhagic crust and become dry over 7-10 days; lesions are infectious until dry; sensory prodrome (pain, pruritus, or paresthesias) in 75% of cases and mild systemic response (headache, malaise, anorexia, etc) can precede presentation; thoracic dermatome most commonly involved


  • Disseminated zoster, defined as generalized eruption of more than 10-12 extradermatomal vesicles occurring 7-14 days after onset of classic dermatomal zoster, is seen in 2% of cases in general population and up to 35% in immunocompromised patients; observe these patients carefully for development of visceral involvement (liver, lung, brain) as pneumonitis and encephalitis can be life-threatening


  • Atypical presentation in AIDS pts: >2 dermatomes affected, may cross midline, may present with verrucous/crusted lesions


  • Complications: post-herpetic neuralgia (PHN), scarring, secondary bacterial infection, meningoencephalitis, Ramsay-Hunt syndrome, ocular blindness, motor paralysis


  • Postherpetic neuralgia (PHN): pain that continues after resolution of the eruption, typically lasting more than 30 days (some experts prefer to reserve the term for pain that lasts more than 90 days); occurs in 10-25% of cases


  • Ocular involvement: lesions on tip of nose signal possible ocular infection (since nasociliary nerve involved, a branch of the ophthalmic nerve)


  • Ramsay-Hunt syndrome: infection of geniculate ganglion → ear canal/auricle/tympanic membrane involvement with painful vesicles, facial paralysis/paresis, ipsilateral hearing loss


  • Treatment: antiviral best if within 48-72 h within appearance of rash (can ↓ PHN risk); of note, concomitant corticosteroid use has no effect on development/duration of PHN; IV acyclovir used in immunocompromised patient if advanced HIV, widespread skin involvement, visceral disease or transplant patients


  • Of note, women with varicella infection 5 days before or 2 days after delivery, can result in severe acute infection of newborn (neonatal varicella, mortality of newborn up to 30%); different from VZV embryopathy or congenital varicella syndrome which occurs in first 20 weeks of pregnancy



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Figure 4.3:
A: Disseminated varicella in HIV patient(Courtesy of Dr. Sophie M. Worobec)B: Herpes zoster, trunkC: Herpes zoster, magnified


Epstein-Barr Virus (EBV, HHV4)





  • Infects B lymphocytes and establishes lifelong asymptomatic infection in these cells and mucosal epithelial cells


  • Causes infectious mononucleosis (IM), oral hairy leukoplakia (OHL), Gianotti-Crosti syndrome, Hodgkin’s lymphoma, endemic Burkitt’s lymphoma, post-transplant lymphoproliferative disorder (PTLD), nasopharyngeal carcinoma, and NK cell lymphoma


  • Of note, morbilliform eruption typically occurs in patient with mononucleosis if ampicillin or amoxicillin given


Cytomegalovirus (CMV, HHV5)





  • Asymptomatic/subclinical infection in healthy persons, but severe infections in infants infected before birth and immunosuppressed patients (especially with HIV or organ transplant); transmission via body fluids


  • Immunosuppressed patients: infection can lead to ocular (CMV necrotizing retinitis), CNS (meningoencephalitis), GI tract (inflammation with painful ulcerations), and lung abnormalities (pneumonitis)


  • Presents with wide variation: asymptomatic or mono-like symptoms; polymorphous eruption including vesicles, nodules, or verrucous plaques


  • Histology: cytomegalic endothelial and/or epithelial cells enlarged with intranuclear inclusions, eccentrically displaced nucleus with halo (‘owl’s eye’ inclusion bodies)


  • In AIDS can present with chronic perianal and lower extremity ulcerations, esophagitis, pneumonitis, chorioretinitis


  • Treatment of choice is ganciclovir


HHV6





  • Etiologic agent of exanthem subitum (roseola infantum or sixth disease)


  • Transmission via saliva with lifelong latency after primary infection


  • Complications infrequent in healthy patients: most common include febrile seizures


  • Treatment: no treatment required in healthy patients


HHV7





  • Epidemiology similar to HHV6


  • Not clearly associated with any clinical disease, but it has been linked to several conditions such as exanthem subitum and pityriasis rosea (Figure 4.4A-C, 4.5A)



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Figure 4.4:
A: Pityriasis rosea, herald patchB: Pityriasis roseaC: Pityriasis rosea(Courtesy of Dr. Paul Getz)


HHV8 (Kaposi Sarcoma-Associated Herpesvirus [KSHV]) (Figure 4.5B)





  • Etiologic agent of all types of Kaposi’s sarcoma (KS)


  • Four types of KS:



    • Classic: indolent, purple-red plaques on lower extremities in elderly men from Mediterranean descent, slow progression, rare involvement of GI tract and oral mucosa


    • AIDS-related: widely-distributed purpuric macules, patches and plaques on skin, oral and genital mucosa, GI tract and lung


    • Immunosuppression-associated: similar to AIDS-related KS with aggressive nature and dissemination


    • African endemic: aggressive, young patients in equatorial Africa, unrelated to HIV, subtypes include nodular, lymphadenopathic, florid and infiltrative


  • Other conditions associated with HHV8: Castleman’s disease (non-malignant lymphoproliferative disorder) and primary effusion lymphoma


  • Histology: spindle cells forming slit-like vascular channels with surrounding hemosiderin, promontory sign


  • Treatment: topical retinoid, surgery, radiotherapy, cryotherapy, systemic chemotherapy for extensive disease, HAART if AIDS-related


B. HUMAN PAPILLOMAVIRUS (HPV) (Table 4-1)






  • Non-enveloped dsDNA virus with more than 100 different HPV types; infects epithelia and mucosa


  • Genome encodes ‘E’ (early) and ‘L’ (late) proteins



    • ‘E’ proteins (E1-E7) code for viral DNA replication; E6 and E7 oncogenes lead to keratinocyte immortalization; low levels expressed in basal layer


    • ‘L’ proteins (L1 and L2) code for viral structural proteins (form outer shell: virion), expressed in superficial epithelium


  • Transmission mainly via direct skin contact, less likely via fomites; basal keratinocyte target of HPV (long-term reservoir of viral DNA)


  • Divided into nongenital and genital infections; also divided into benign or low risk (HPV 6/11) and high risk (HPV 16/18) types


  • Gardasil® vaccine: composed of L1 capsid protein with 4 types of recombinant HPV (type 6, 11, 16, 18)


  • Cervarix® vaccine: L1 protein for HPV 16 and 18


  • Clinical manifestations of HPV infection:



    • Common, plantar, and flat warts (Figure 4.5C)


    • Condyloma acuminata: lesions without significant scale in genital area


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Figure 4.5:
A: Pityriasis rosea, face(Courtesy of Dr. Paul Getz)B: Kaposi’s sarcoma(Courtesy of National Cancer Institute)C: Verruca vulgaris



Table 4-1:
HPV Subtypes




























































Lesion

HPV types (frequent)

HPV types (less frequent)

Common wart

1, 2, 4

26, 27, 29, 41, 57, 60, 63, 65

Plantar wart

1

2, 4, 63

Flat wart

3, 10

28, 29

Butcher’s wart

2, 7

1, 2, 3, 4, 10, 28

Epidermodysplasia verruciformis (EV)

2, 3, 5, 8–10, 12, 14, 15, 17

19–25, 36–38, 46, 47, 49, 50

Focal epithelial hyperplasia (Heck’s)

13, 32
 

Verrucous carcinoma

6, 11
 

Condyloma acuminata

6, 11

40, 42–44, 51, 54, 55, 61, 70, 72, 81

Bowenoid papulosis

16, 18

26, 31, 33, 35, 39, 45, 51–53, 56, 58, 59, 62, 66, 68, 73

Digital SCC

16

34, 35

SCC (in EV)

5, 8

14, 17, 20, 47

Cervical cancer

16, 18

31, 33, 35, 39, 45, 51, 52, 56, 58, 66, 68, 70









    • Bowenoid papulosis: red-brown papules or plaques involving genital and/or perineal area (clinically appear as genital warts, but histology consistent with Bowen disease) (Figure 4.6A)


    • Verrucous carcinoma: ‘semi-malignant’ (Figure 4.6B-D)



      • Florid oral papillomatosis: widespread verrucous carcinoma in oral cavity


      • Buschke-Lowenstein tumor: large cauliflower-like tumor of anorectum and external genital, focal malignant transformation may occur


      • Epithelioma cuniculatum of sole: slow-growing warty mass on sole


    • Focal epithelial hyperplasia (Heck’s disease): papules on buccal, gingival, labial mucosa resembling flat warts


    • Epidermodysplasia verruciformis: sporadic or AR inheritance, abnormal susceptibility of skin to HPV; red-brown macules with mild scale on face/trunk or flat-topped papules on hands resembling flat warts (malignant transformation in 50% patients)





  • Histology: papillomatosis, massive orthokeratosis, columns of parakeratosis, coarse keratohyalin granules of variable size, vacuolated cells (koilocytes), dilated and thrombosed capillaries


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Figure 4.6:
A: Bowenoid papulosis*B: Epithelioma cuniculatum of sole*C: Buschke-Lowenstein tumor*D: Florid oral papillomatosis**Reprint from Baykal C, Yazganoğlu KD (eds). Clinical Atlas of Skin Tumors. Heidelberg, Germany. Springer; 2014.


C. POXVIRUS INFECTIONS





Table 4-2:
Select Poxvirus Infections




















































Disease

Virus

Clinical Findings

Treatment

Comments

Molluscum Contagiosum

Molluscipox


Molluscum contagiosum virus

Umbilicated pink, firm waxy papules seen mainly in children

If adult with genital lesions, likely sexual transmission

Larger lesions seen in patients with AIDS

Usually self-limited

Treatment: cantharidin, cryosurgery, curettage, imiquimod

Henderson- Patterson molluscum bodies (intracytoplasmic inclusion bodies)

Orf

(Contagious Pustular Dermatosis)

(Ecthyma Contagiosum)

(Figure 4.7A)

Parapox


Orf virus

One to few papules at contact site with infected goat/sheep, ± fever, lymphadenitis; 6 clinical stages (in order: maculopapular, targetoid, acute, regenerative, papillomatous, regressive)

Supportive treatment as self-limited

Mainly in shepherds, veterinarians, goat herders, and butchers

Milker’s nodule

(Pseudocowpox)

(Paravaccinia)

Parapox


Paravaccinia virus

Presents as solitary red-purple nodule on finger with slow growth or with multiple cherry-red nodules at inoculation site

Supportive treatment as self-limited

Recent contact with infected cows, calves, or viral fomites

Vaccinia

Orthopox


Vaccinia

virus

Local reaction to site of vaccination (erythema or pruritic papule)

Eczema vaccinatum (in atopic patients): diffuse infection in eczematous skin

Supportive; heals with pitted scarring

Live virus used for smallpox vaccine

Smallpox

(Figure 4.7B)

Orthopox


Variola

virus

Prodrome (backache, fever) after incubation period (12–14 days)

Macules/papules initially on face, spreads to trunk and extremities → papules turn to vesicles/pustules with central umbilication

Respiratory and contact isolation, vaccination if early

All lesions same stage of development

Transmission via respiratory droplets

Cowpox

Orthopox


Cowpox

virus

Painful inflamed macule or papule at contact site with infected cow → vesicular, then pustular with tendency to ulcerate → deep-seated black eschar with erythema

Supportive as self-limited; heals with scarring

Eschar with surrounding edema/erythema similar to cutaneous anthrax


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Figure 4.7:
A: Orf* B: Smallpox***Reprint from Lipsker D (ed). Clinical Examination and Differential Diagnosis of Skin Lesions. Paris, France; Springer; 2013.**Reprint from Morgan MB, Smoller BR, Somach SC (eds). Deadly Dermatologic Diseases. New York, NY: Springer; 2007.


D. MISCELLANEOUS (Tables 4-3 and 4-4)





Table 4-3:
Classification of Viruses








































RNA

dsDNA

ssDNA

Togavirus (rubella)

Herpesvirus (HSV, CMV, EBV, KSHV)

Parvovirus

Flavivirus (HCV, dengue fever, yellow fever)

Hepadnavirus (HBV)
 

Orthomyxovirus (influenza)

Adenovirus
 

Rhabdovirus (rabies)

Papovavirus (papillomavirus, JC virus)
 

Picornavirus (rhinovirus, hepatovirus [HAV], enterovirus [poliovirus, enterovirus, coxsackievirus, echovirus])

Poxvirus (molluscipox, orthopox, parapox)
 

Paramyxovirus (measles, mumps, RSV)

DNA virus mnemonic: HHAPPPy
 

Retrovirus (HIV, HTLV)
   



Table 4-4:
Select Vaccinations
















































Live Attenuated Virus

Killed Virus

Purified Products

Influenza (nasal spray, FluMist®)

Influenza (injection)

Pneumococcus (Pneumovax®)

Yellow fever

Rabies

Tetanus

Typhoid (oral)

Typhoid (injection)

Hepatitis B

Polio (oral)

Polio (injection)

Diphtheria

Rubella

Hepatitis A

HPV (Gardasil®)

Mumps

Cholera

HPV (Cervarix®)

Measles

Bubonic plaque
 

BCG (M. bovis)
   

VZV (Zostavax®)
   

Live Virus: ROMe Is MY Best Vacation: rubella, oral polio, mumps, influenza, measles, yellow fever, bcg, varicella

Killed/Purified Virus:

Rest in PPPeace Always:

rabies, influenza, polio (injection), pneumococcus, papillomavirus, A hepatitis (and B)


4.2 Bacterial Infections



A. GRAM-POSITIVE INFECTIONS



STAPHYLOCOCCAL INFECTIONS:






  • S. aureus: aerobic, gram-positive catalase-positive bacteria arranged in clusters


  • Best defense: intact skin


  • MRSA: ↑ resistance to methicillin caused by staphylococcal chromosome cassette mec (SCC mec), specifically mecA gene (encodes alternative penicillin-binding protein, PBP2a)


  • Select S. aureus toxins:
















Toxic shock syndrome toxin-1 (TSST-1)

Superantigen, involved in toxic shock syndrome (TSS)

Exfoliative toxin (ET-A, ET-B)

Protease activity, splits epidermal desmoglein 1, involved in staphylococcal scalded skin syndrome (SSSS) and bullous impetigo

Panton-Valentine leukocidin (PVL)

In many community acquired MRSA strains, associated with ↑ virulence (leukocyte destruction, necrosis)


Impetigo (Figure 4.8A-B)





  • Highly contagious infection seen primarily in children


  • Two types: bullous and nonbullous


  • Nonbullous: S. aureus most common cause, less common Gr. A strep (GAS)



    • Erythematous macule → pustule/vesicle → erosion with golden crust (+ culture from exudate under crust)


  • Bullous: S. aureus ONLY (usually phage II, type 71)



    • Flaccid, transparent bullae → rupture leaving shiny, dry erosion with no surrounding erythema, ± fever, diarrhea, weakness


    • Cleavage at granular layer due to ET (A/B) binding to desmoglein 1; S. aureus at site of lesion

Unlike SSSS





  • Treat with topical mupirocin, if extensive can use oral antibiotic (ie. cephalexin, dicloxacillin, etc)


Staphylococcal Scalded Skin Syndrome (SSSS) (Figure 4.8C)





  • Exfoliative disease mainly in neonates and young children; can occur in adults with renal insufficiency or if immunocompromised (mortality > 50%)


  • Presents with fever, conjunctivitis, initial tenderness of skin and erythema over body folds → generalized wrinkled appearance with subsequent exfoliation (‘sad man’ facies),


  • perioral crusting/fissuring, + Nikolsky sign


  • S. aureus phage II (types 3A, 3C, 55 or 71) at a distant site (extralesional): ET (A/B) → binds desmoglein 1 in granular layer causing superficial bulla


  • Culture of bullae → negative (infection at remote site)


  • Treatment: penicillinase-resistant penicillin (ie. dicloxacillin) and IV fluid support



A327767_2_En_4_Fig8_HTML.jpg


Figure 4.8:
A: Impetigo(Courtesy of Dr. Paul Getz)B: Bullous impetigo, armC: SSSS(Reprint from Allen HB. Dermatology Terminology. New York, NY: Springer; 2010.)


Toxic Shock Syndrome (TSS) (Figure 4.9A)





  • Multisystem illness due to S. aureus, initially in women with use of superabsorbent tampons, but now more commonly seen in infections with wounds, catheters, deep abscesses, or nasal packing


  • Superantigen-mediated TSST-1 results in polyclonal T cell activation → cytokine storm (TNF, IL-1, etc)


  • Presentation:



    • Four criteria: fever, hypotension, macular exanthem, and involvement of three or more organ systems


    • Exanthem: diffuse scarlatiniform exanthem on trunk spreading outward, palmoplantar edema and erythema (with desquamatiion 1-3 weeks later), hyperemia of conjunctiva


  • Treatment: remove any nidus of infection, parenteral β-lactamase resistant antibiotic, and fluid support


Bacterial Folliculitis





  • Superficial infection of hair follicle usually due to S. aureus


  • Presents with pustules in follicular distribution associated with hairs


  • Treatment: antibacterial wash (chlorhexidine or triclosan), antibacterial ointments (mupirocin), and if widespread can use oral antibiotic


Furuncle, Carbuncle, Abscess (Figure 4.9B-C)





  • Typically due to S. aureus


  • Depth of infection determines presentation


  • Furuncle: deep-seated tender nodule of hair follicle


  • Carbuncle: coalescing of adjacent furuncles with multiple draining sinuses (typically involves nape of neck or back of thighs)


  • Abscess: inflamed walled off collection of pus (Figure 4.10A)


  • Treatment



    • Simple furuncle (no fluctuance): warm compresses


    • Fluctuant furuncle or abscess: incision and drainage


    • Oral antibiotics if:



      • Located near midface (concern for cavernous sinus thrombosis) or external auditory canal


      • Recurrent or recalcitrant to local area alone


      • Very large or with surrounding cellulitis



A327767_2_En_4_Fig9_HTML.jpg


Figure 4.9:
A: Toxic shock syndrome(Reprint from Morgan MB, Smoller BR, Somach SC. Deadly Dermatologic Diseases. New York, NY: Springer; 2007.)B: FuruncleC: Carbuncle


STREPTOCOCCAL INFECTIONS






  • Gram-positive bacteria arranged in chains or pairs


  • Not part of normal cutaneous flora (but resident of aerodigestive tract and vagina)


  • Classification via two methods:



    • Ability to induce hemolysis (α, β, γ) and/or


    • Lancefield groups (A-D, G) based on characteristic polysaccharide cell wall


    • Of note, group A β-hemolytic streptococci (S. pyogenes, GAS) most pathogenic


  • The following antibodies become positive after infection with GAS: anti-streptolysin O (ASO), anti-hyaluronidase, and anti-DNase-B


  • Certain strains with erythrogenic toxins: S. pyogenes exotoxins (SPE-A, SPE-B, SPE-C)


Cellulitis (Figure 4.10B)





  • Infection of the deep dermis and subcutaneous tissue, mostly due to GAS (S. aureus less common)


  • In immunocompetent patients, usually first step is a break in the skin barrier


  • Presents as an ill-defined area with erythema, swelling and tenderness, ± fever, chills


  • Treatment: oral antibiotic with good Gram-positive coverage


Erysipelas (St. Anthony’s Fire) (Figure 4.10C)





  • Superficial type of cellulitis with significant dermal lymphatic involvement; typically due to GAS


  • Presents as a well-defined, bright red indurated plaque with sharp, raised borders commonly on the face or legs, ± constitutional symptoms


  • Treatment of choice: PCN (if PCN-allergic can use macrolide)


Blistering Distal Dactylitis





  • Unique GAS bullous eruption in children


  • Tense stable blisters on tender erythematous base over volar tips of toes or fingers


  • Treatment: dicloxacillin or first-generation cephalosporin


Necrotizing Fasciitis





  • Rapidly progressive necrosis of subcutaneous tissue and fascia due to GAS, but typically mixed infection with 30% mortality rate


  • Risk factors include advanced age, diabetes, peripheral vascular disease and/or history of alcohol abuse


  • Presents as tender, erythematous tense plaques recalcitrant to antibiotics and progresses at an alarming rate → necrosis of fascia and fat renders watery foul-smelling fluid


  • Treatment: extensive surgical debridement



A327767_2_En_4_Fig10_HTML.jpg


Figure 4.10:
A: Abscess(Courtesy of Dr. Paul Getz)B: Cellulitis(Courtesy of Dr. Paul Getz)C: Erysipelas(Courtesy of CDC: Dr. Thomas Sellers, Emory University)


Perianal Streptococcal Disease (Figure 4.11A)





  • Perianal GAS infection typically in preschool children


  • Presents with circular band of erythema around anus, ± painful defecation, blood-streaked stools, anal leakage


  • Obtain both throat and perianal culture; treat with PCN or erythromycin × 10-14 days

Do not confuse with ecthyma gangrenosum


Ecthyma (Figure 4.11B)





  • Deeper form of nonbullous impetigo with ulceration due to GAS but quickly contaminated by S. aureus


  • Presents as ‘punched out’ shallow ulcer with thick, yellow-gray crust commonly in lower legs of children


  • If diagnosis uncertain → punch biopsy with deep-tissue Gram stain and culture


  • Treatment: dicloxacillin or first generation cephalosporin


Scarlet Fever (Figure 4.11C)





  • Diffuse exanthem from GAS pharyngitis with erythrogenic toxin (SPE-A, B, C); mainly in children


  • Presents with sore throat, headache, fever → tiny pink papules on erythematous background (sandpaper-like), linear petechiael streaks along body folds (Pastia’s lines), circumoral pallor, palatal petechiae, ‘strawberry tongue’ initially white then red


  • Treatment: PCN or erythromycin × 10-14 days


Streptococcal Toxic Shock Syndrome (STSS)





  • Rapidly progressive multi-organ illness, high mortality (30-60%), caused by GAS


  • Superantigen mediated: SPE-A → stimulates T cells with massive cytokine release → subsequent shock


  • Presents typically with sudden onset pain in an infected soft tissue, flu-like symptoms, CNS symptoms (confusion, coma) → multi-organ failure


  • Generalized exanthem less common in STSS (vs. TSS), and STSS more likely in an otherwise healthy adult


  • Treatment: intensive supportive therapy, IV penicillinase-resistant PCN or oral clindamycin (latter may more rapidly shut down toxin production)



A327767_2_En_4_Fig11_HTML.gif


Figure 4.11:
A: Perianal strep(Reprint from Al-Jasser M, Al-Khenaizan S. Cutaneous mimickers of child abuse. Eur J of Ped. 2008; 167(11): 1221-30.)B: Ecthyma(Courtesy of Dr. Paul Getz)C: Strawberry tongue(Reprint from Allen HB. Dermatology Terminology. New York, NY: Springer; 2010.)


CORYNEBACTERIAL INFECTIONS






  • Corynebacterium: gram-positive rod-shaped bacteria


Erythrasma (Figure 4.12A-B)





  • Superficial infection in occluded intertriginous areas due to C. minutissimum


  • Presents as well-demarcated red-brown macules/patches with fine scale and wrinkling in intertriginous areas; interdigital maceration and scaling between toes


  • Most common bacterial infection of the foot


  • Wood’s lamp: bright coral-red fluorescence due to porphyrin production (coproporphyrin III)


  • Treatment: topical antibiotic or antifungal (clindamycin, erythromycin, imidazole) or oral erythromycin × 5 days


Trichomycosis Axillaris





  • Superficial bacterial colonization with C. tenuis of hair shafts in axilla; ↑ risk with hyperhidrosis/poor hygiene


  • Presents with white-yellow, red or black adherent nodules attached to hair shafts (‘frosted’ appearance of hairs) with characteristic rancid acidic odor, common in axilla and rarely affects pubic area


  • Treatment: shave axillary hair, topical benzoyl peroxide or topical clindamycin


Pitted Keratolysis (Figure 4.12C-D)





  • Non-inflammatory infection due to Corynebacteria spp. or Kytococcus sedentarius (previously called Micrococcus)


  • Bacteria produce keratin-degrading proteases


  • Presents with asymptomatic shallow crater-like depressions over weight-bearing areas of feet, accompanying hyperhidrosis and malodor


  • Treatment: topical clindamycin, erythromycin or benzoyl peroxide



A327767_2_En_4_Fig12_HTML.jpg


Figure 4.12:
A: ErythrasmaB: Erythrasma (Wood’s light)C: Pitted keratolysis(Courtesy of Dr. Paul Getz)D: Pitted keratolysis(Courtesy of Dr. Paul Getz)


Cutaneous Diphtheria (Figure 4.13A)





  • Localized infection of C. diphtheriae, endemic in several tropical countries, skin involvement via inoculation to an otherwise insignificant wound


  • Presents as sharply bordered, punched out ulcer with yellow leathery pseudomembrane (primary disease) or pre-existing wound becomes infected (secondary disease)


  • If toxin produced, risk of cardiac or neurologic disease


  • Treatment: diphtheria antitoxin from horse serum (before toxin binds cells) crucial, PCN or erythromycin × 10-14 days


Other Gram-Positive Infections



Anthrax (Malignant Pustule) (Figure 4.13B)





  • Acute disease in humans and animals caused by Bacillus anthracis, a Gram-positive spore-forming rod


  • Clinical forms: cutaneous, pulmonary, and GI


  • Cutaneous form: ‘malignant pustule’ at inoculation site which spreads and becomes hemorrhagic → central eschar with surrounding nonpitting edema → eschar sloughs leaving shallow ulceration


  • Virulence factors: capsule and 2 exotoxins: edema toxin (increases cAMP levels) and lethal toxin (increases TNFα and IL1β promoting shock/death)


  • Bioterrorism-associated treatment: ciprofloxacin or doxycycline (conventional treatment: PCN)


Erysipeloid (Fish Handler’s Disease) (Figure 4.13C)





  • Infection caused by Erysipelothrix rhusiopathiae through direct contact with infected meat, seen mainly in meat-handlers, fisherman or veterinarians


  • Presents with painful red to purple patches over hands (finger webs often involved, sparing terminal phalanges) with sharply-marginated spreading edge, possible central clearing and/or hemorrhagic vesicles


  • Systemic form with fever, arthralgias, widespreaed cutaneous lesions, possible sepsis and fatal endocarditis


  • Treatment: penicillin (if PCN allergy → erythromycin)


Gas Gangrene (Clostridial Myonecrosis)





  • Most severe form of infectious gangrene developing in deep lacerated wounds of muscle tissue caused by Clostridium spp. and subacute variety due to other bacteria


  • Presents with severe localized pain with sudden onset and accompanying fever/chills; physical exam shows crepitation on palpation and characteristic mousy odor


  • Treatment is wide surgical debridement and extensive antibiotic therapy



A327767_2_En_4_Fig13_HTML.gif


Figure 4.13:
A: Cutaneous diphtheria(Courtesy of Public Health Image Library: CDC)B: Cutaneous anthrax(Courtesy of James Steele, CDC)C: Erysipeloid(Reprint from Mandell G, ed. Atlas of Infectious Diseases. Philadelphia, PA: Current Medicine LLC; 2002.)


Actinomycosis (“Lumpy Jaw”) (Figure 4.14A-B)





  • Due to Actinomyces israelii, an anaerobic filamentous Gram-positive bacteria; part of normal oral flora


  • Risk factors: poor dental hygiene, dental procedures, traumatic injuries


  • Presents as a firm nodule or bluish swelling at angle of jaw → direct spread into adjacent tissues → formation of fistulas discharging purulent material with granules (yellow sulfur-like appearance consisting of masses of bacteria, both gram-negative and gram-positive)


  • Treatment: intravenous PCN initially, then switch to oral PCN × 6-12 months


Actinomycetoma (Madura Foot) (Figure 4.14C)





  • Suppurative infection caused by bacteria (actinomycetoma) or fungus (eumycetoma)


  • Bacterial infection due to Nocardia brasiliensis, Nocardia asteroides , Actinomadura madurae, Actinomadura pelletieri , Streptomyces somaliensis


  • Presents as painless nodules at site of trauma (typically on foot) → increases in size with purulence, tumefaction, draining sinuses and exudate containing grains


  • N. brasiliensis → primary cutaneous nocardiosis (lymphocutaneous infection, mycetoma or superficial infection [ulceration, abscess, cellulitis])


  • N. asteroides → disseminated nocardiosis (10% disseminated to skin in patients with systemic nocardial infection)


  • Treatment: surgical debridement/azole antifungal (eumycotic) or bactrim/streptomycin (actinomycotic)
























Grain Color

Organism

White

Nocardia brasiliensis, Nocardia asteroides

Pink or cream

Actinomadura madurae

Yellow to brown

Streptomyces somaliensis

Red

Actinomadura pelletieri


B. GRAM-NEGATIVE INFECTIONS



PSEUDOMONAL INFECTIONS






  • Pseudomonas aeruginosa: gram-negative bacteria, grows well in aqueous environment, has ability to produce variety of pigments:°Greenish-blue pyocyanin° Yellow-green fluorescein° Brown-black pyomelanin


Green Nail Syndrome (Figure 4.14D)





  • Subungual pseudomonal infection causing green discoloration of nail and onycholysis


  • Treatment: trim nail, acetic acid soaks, topical ciprofloxacin or thymol solution



A327767_2_En_4_Fig14_HTML.gif


Figure 4.14:
A: Actinomycosis(Courtesy of Dr. Paul Getz)B: Actinomycosis, chest(Courtesy of Dr. Vandana Mehta, India)C: Actinomycetoma, arm(Courtesy of Dr. Paul Getz)D: Green nail syndrome


Ecthyma Gangrenosum (Figure 4.15A)





  • Cutaneous manifestation of severe, invasive infection by P. aeruginosa typically in immunosuppressed patients


  • Presents initially as erythematous macules → opalescent, tense vesicles or pustules → hemorrhagic and violaceous vesicles → rupture and form ulcers with necrotic centers


  • Treatment: intravenous aminoglycoside with anti-pseudomonal penicillin


Pseudomonas Hot Foot Syndrome





  • Painful plantar purple-red nodules after exposure to pool water contaminated with P. aeruginosa


  • Self-limited


Pseudomonal Folliculitis (Hot Tub Folliculitis)





  • Folliculitis due to nonpathogenic strain of P. aeruginosa


  • Presents with erythematous follicular papules and pustules at sites of exposure to water (via whirlpool, hot tub, rarely swimming pool) with sparing of face and neck


  • Self-limited in immunocompetent person


Pseudomonal Pyoderma





  • Superficial infection of skin with P. aeruginosa with ‘mousy’ odor


  • Presents typically on feet with macerated ‘moth-eaten’ appearance, green-blue purulence and eroded borders


  • Blastomycosis-like pyoderma presents as verrucous plaques with elevated borders and pustules as a chronic vegetating infection


Other Gram-Negative Infections



Acute Meningococcemia (Figure 4.15B-C)





  • Acute and potentially life-threatening infection of the blood vessels caused by Neisseria meningitidis, an encapsulated gram-negative diplococcus


  • Bacterial carriage via nasopharynx


  • Presents initially with erythematous macules/papules → evolve to stellate purpuric patches/plaques with ischemic necrosis and/or hemorrhage, accompanied by high fever and toxic appearance


  • Recurrent infections in patients with defects in late components of complement (C5-C9)


  • Treatment: high dose IV PCN (if resistant, use 3rd generation cephalosporin)



A327767_2_En_4_Fig15_HTML.jpg


Figure 4.15:
A: Ecthyma gangrenosumB: Meningococcemia(Courtesy of Dr. Paul Getz)C: Meningococcemia(Courtesy of Dr. Paul Getz)



Table 4-5:
Select Gram-Negative Infections

































































Disease

Etiology/Vector

Clinical Findings

Treatment

Glanders

Burkholderia mallei

Contact with infected horses

Ulcerated nodule at inoculation site with regional lymphadenopathy, ± ‘farcy buds’ (nodules along lymph nodes)

Sulfonamide

Brucellosis

(Undulant fever)

(Malta fever)

Brucella spp.

Direct contact with infected animal or ingestion of dairy (unpasteurized)/infected meat

Cyclic fevers, arthralgias, hepatospleno-megaly; rare skin involvement (violaceous papulonodular eruption)

↑ Risk: butchers, farmers, veterinarians

Doxycycline combined with rifampin

Tularemia

(Rabbit fever)

(Deer fly fever)

Francisella tularensis

Direct contact with wild animals like rabbits (rabbit-borne), ticks (tick-borne) or deer flies

Ulceroglandular: tender chancre-like papule or nodule with lymphadenopathy, lymph nodes may become fluctuant with suppuration

↑ Risk in hunters

Streptomycin

Vibrio infection

Vibrio vulnificus

Ingestion of raw seafood or open wound exposed to seawater

Fever, chills, abdominal pain, red to violaceous macules → painful hemorrhagic bullae with cellulitis

↑ Risk: diabetes, liver disease, immunosuppression

Oral TCN

Plague

Yersinia pestis

Transmitted via flea bite from infected animals

Myalgias, malaise, fever → small papule/pustule at site of flea bite with swollen, painful fluctuant lymph nodes (‘buboes’)

Streptomycin (IM)

Malakoplakia

E. coli

Pseudomonas aeruginosa, Proteus, Klebsiella)

Commonly affects urinary tract, rare skin involvement with weeping perianal plaque or polypoid mass

Histo: Michaelis-Gutmann bodies

Cipro (long-term) or surgical removal

Rhinoscleroma

Klebsiella rhinoscleromatis

Transmission via inhalation of droplets or contaminated material

Infectious granulomas in nasal mucosa and respiratory tract, epistaxis, Hebra nose (destruction of nasal cartilage)

Histo: Mikulicz cell, Russell bodies

Cipro

Rat-Bite Fever

(Haverhill fever)

Streptobacillus moniliformis

Direct contact from rodents or contaminated food

Fever, arthritis, ± ulceration at site of bite and generalized morbilliform eruption with acral distribution

Penicillin

Cat Bite

Pasteurella multocida

Erythema, pain, tenderness with gray serous drainage from puncture wound

Augmentin, irrigate site, ± tetanus prophylaxis

Dog Bite

Capnocytophaga canimorsus

Pasteurella canis

Pasturella multocida

Human Bite

Eikenella corrodens


Bartonella Infections






  • Gram-negative, facultative intracellular bacteria


  • Can infect healthy individuals but considered especially important as an opportunistic pathogen


  • Transmitted via insect vectors (ticks, fleas, sand flies, and mosquitoes)


  • Adheres to and invades erythrocytes (B. bacilliformis)


  • All three types can produce an endothelial cell-stimulating factor → proliferation of both endothelial cells and blood vessels



Table 4-6:
Select Bartonella Infections


































Disease

Etiology/Vector

Clinical Findings

Treatment

Oroya Fever

(Carrion’s disease)

(Verruga peruana) (Figure 4.16A)

(Peruvian wart)

Bartonella bacilliformis

Vector: sandfly Lutzomyia verrucarum

Biphasic disease:

Acute stage (Oroya fever):

 fever + hemolytic anemia

Chronic stage (verruga peruana):

 erythematous papules/nodules, resolves spontaneously but may persist for years

Acute stage: chloramphenicol (covers salmonella coinfection)

Chronic stage: TCN or PCN

Cat-Scratch Disease

Bartonella henselae

Vector: cat flea Ctenocephalides felis

Transmission via cat bite or scratch (flea feces inoculated into scratch site)

Unilateral tender lymphadenitis 2-4 weeks after cat scratch, typically in axilla > epitrochlear node (can last between 2–5 months)

Parinaud oculoglandular syndrome: unilateral conjunctivitis and regional lymphadenitis

Rare atypical manifestations: encephalitis, pneumonia, erythema nodosum, arthralgia, thrombocytopenic purpura

Spontaneous resolution typical

If patient immunosuppressed treat with doxycycline or erythromycin

Bacillary Angiomatosis

Bartonella henselae

Bartonella quintana

Vector: lice, ticks, fleas

Erythematous tender papules and nodules resembling pyogenic granulomas, seen mainly in HIV patients

Doxycycline or erythromycin

Trench Fever

(Shin bone fever)

Bartonella quintana

Vector: body louse

Pediculus humanus var. corporis

Also causes epidemic typhus

Fever (relapsing), chills, tenderness of shins, back pain, and transient macular eruption

↑ Risk: crowding and poor hygiene

Doxycycline or erythromycin


A327767_2_En_4_Fig16_HTML.jpg


Figure 4.16:
A: Verruga peruana(Reprint from Silverberg NB, Durán-McKinster C, Tay Y-K (eds). Pediatric Skin of Color. New York, NY. Springer; 2015.)B: Rocky Mountain spotted fever(Reprint from Morgan MB, Smoller BR, Somach SC (eds). Deadly Dermatologic Diseases. New York, NY: Springer; 2007.)


Rickettsiae






  • Gram-negative, motile, pleomorphic bacteria; obligate intracellular parasite (usually infecting endothelial cells, causing vasculitis)


  • Bacteria carried as parasites by many ticks, fleas, and lice


  • Includes R. rickettsii , R. akari , R. conori , R. prowazekii , R. typhi , R. tsutsugamushi (latter reclassified into genus Orientia)


  • Few bacteria which are morphologically similar to Rickettsiae: Coxiella burnetii and Ehrlichia



Table 4-7:
Select Rickettsial Infections






















































Disease

Organism/Vector

Clinical Findings

Treatment

Rocky Mountain Spotted Fever (RMSF) (Figure 4.16B)

R. rickettsii

Vector: tick

Dermacentor andersoni (wood tick in Western US)

Dermacentor variabilis (dog tick in Eastern US)

Fever, headache, myalgias → purpuric or hemorrhagic macules and papules on wrists/ankles initially → spreads to trunk, hands, feet (‘spotless’ in 10-20% cases)

Mortality 15-25% if untreated

Doxycycline preferred treatment (in pregnant patients may use chloramphenicol)

Mediterranean Spotted Fever(Boutonneuse fever)

R. conorii

Vector: brown dog tick Rhipicephalus sanguineus

Two forms:

Tache noir: indurated papule at site of tick bite → necrotic ulcer

Exanthem: erythematous papules

 mainly over lower limbs

Doxycycline or chloramphenicol

Rickettsialpox

R. akari

Vector: mouse mite

Liponyssoides sanguineus (formerly Allodermanyssus)

Initial papule or vesicle at site of bite → Eschar, regional lymphadenopathy → Sudden-onset fever, chills, headache, diffuse vesicular rash (self-limited)

Doxycycline or chloramphenicol

Epidemic Typhus

(Louse-borne)

R. prowazekii

Vector: body louse Pediculosis humanus var. corporis

Reservoir: flying squirrel

Fever, chills, headache → pale red macules on trunk → evolve to petechiael papules, spread to rest of body (spare face, palms, and soles)

Vascular inflammation of skin, CNS, heart, kidneys and muscle

Doxycycline or chloramphenicol

Endemic Typhus

(Flea-borne)

(Murine typhus)

R. typhi

Vector: rat flea

Xenopsylla cheopis

Fever, headache, myalgias with transient truncal maculopapular exanthem

Doxycycline or choramphenicol

Scrub Typhus

(Mite-borne typhus)

R. tsutsugamushi (now Orientia)

Vector: chigger mites

Trombiculid (larval stage)

Headache, chills, malaise and eschar at site of inoculation with lymphadenopathy → maculopapular rash on trunk, ± pulmonary and cardiac problems

Doxycycline or choramphenicol

Ehrlichiosis

(Monocytic (M) Ehrlichiosis)

(Granulocytic (G) Ehrlichiosis)

E. chaffeensis (M)

E. phagocytophilia (G)

Vector: tick

Ambyloma americanum (M); Ixodes scapularis, Ixodes pacificus (G)

Highly variable exanthem

Tetracycline or doxycycline

Q Fever

Coxiella burnetii

No skin findings; limited febrile illness, severe headache, ± pneumonia, hepatitis, endocarditis

Doxycycline


Spirochetes






  • Gram-negative bacteria with spiral-shaped cells, move via twisting motion (due to axial filaments in the flagella)


  • Include Treponema spp. , Borrelia spp. , and Leptospira spp.



Table 4-8:
Select Spirochete Infections































Disease

Organism/Vector

Clinical Findings

Treatment

Lyme disease

B. burgdorferi

Vector: tick

Eastern US, Great Lakes

Ixodes dammini (also known as I. scapularis)

Western US

Ixodes pacificus

Europe

Ixodes ricinus (reservoir: white-footed mouse)

Principal source (reservoir) of bacteria is white-footed mouse, which tick (larva) feeds on and becomes infected → transmission to humans via infected tick saliva (of note, white-tailed deer is not reservoir for Lyme disease but principal host for adult ticks and are often infected)

Early localized disease: flu-like symptoms + erythema migrans: expanding erythematous patch at site of tick bite with central clearing, occurs ~1-2 weeks after tick bite, average diameter 5cm, disappears typically within 4 weeks without treatment

Early disseminated disease: oval-shaped widespread patches (satellite erythema migrans lesions) due to spirochetemia, neural involvement (facial nerve common), migratory joint pain, carditis

Chronic disease: persistent neurologic and rheumatologic symptoms, acrodermatitis chronic atrophicans: loss of subcutaneous fat with thin, atrophic skin

Diagnosis:

PCR, tissue culture, serologic evidence

Treatment:

Adults, children (>8 y/o): Doxycycline × 14-21 days

Pregnant women, children (<8 y/o):

Amoxicillin × 14-21 days

Borrelial lymphocytoma

(Lymphocytoma cutis)

B. afzelli

B. garinii

(neither present in North America – only Europe)

Firm bluish-red tumor or plaque appears most commonly on ear lobes of children or nipple/areola in adults, less commonly involves genitalia, trunk or extremities

Doxycycline

Relapsing fever

(Louse-borne)

B. recurrentis

Vector: body louse

Pediculus humanus var. corporis

Paroxysmal fevers, myalgias, no specific cutaneous findings

Doxycycline

Relapsing fever

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Aug 7, 2017 | Posted by in Dermatology | Comments Off on Infectious Diseases
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