Infectious

Question 1

Molluscum epidemiology

Answer 1

• Subtypes:
  
  • Type 1: majority if infections, kids
  • Type 2: adults, HIV
• Common, assumed that infection follows contact with infected persons or contaminated objects
• More common in children, warmer climates, and then also younger adults with sexual transmission

Question 2

Molluscum clinical

Answer 2

• Risk factors:
  
  • Age
  • Eczema, topical steroid use
  • Immunosuppression –> more widespread
• Incubation period can be up to 6 months
• Shiny, pearly white hemispherical umbilicated papule that shows a central pore
• Can have many, that coalesce and form plaques –> frequently spread
• HIV: widespread and refractory
• Can also occur in scars and tattoos
• Complications:
  
  • patchy eczema
  • can result in EAC, EM
  • Chronic conjunctivitis
  • When resolved: depressed scars, anteoderma-like lesions
• Prognosis:
  
  • Self-limited, but can last up to 5 years. Unlikely to persist past 6 months

Question 3

Molluscum DDx

Answer 3

• Solitary: PG, SCC, KA
• Multiple: plane warts
• HIV: cutaneous cryptococcosis

Question 4

Molluscum histology

Answer 4

• Histology:
  
  • Cellular proliferation results in lobulated epidermal growths which compress the papillae until they appear as fibrous septa between the lobules
  • Large hyaline bodies (molluscum bodies) are the core of the lesion, containing cytoplasmic masses of virus material
  • If long –> can have chronic granulomatous infiltration

Question 5

Molluscum treatment

Answer 5

• Not necessary if minor, will self-resolve
• Associated dry skin/eczema –> emollients
• Reduce risk of transmission
• First line:
  
  • Caustic destruction: cantharadin, trichloroacetic acid –> can be painful to use
  • Irritant: salicylic acid, adapalene, nitric oxide cream potassium hydroxice, benzyl peroxide, lemon myrtle and tea tree oil
  • Surgical irritation: squeezing may stimulate inflammation and clearance
• Second line:
  
  • Immunological: DCP, imiquimod, interferon, cimetidine, intralesional immunotherapy
  • Surgical removal –> curettage, can leave scar
• Third line:
  
  • Cidofovir
  • Paclitaxel

Question 6

Vaccinia

Answer 6

• This is from the small pox vaccination
• Clinically: itchy papule develops at the site of inoculation 3-4 days post vaccination, and can develop into a pustule or blister which may burst
• healed by 3 weeks
• for immunosuppressed or if not covered can spread, and spread to close contacts as well
• Scars, can be site for BCC development
• Manage: cover, avoid close contact with immunosuppressed

Question 7

CowPox

Answer 7

• Natural reservoir of virus is in wild rodents, cattle and zoo animals
• Histology indicates necrotic epidermis with prominent eosinophilic intracytoplasmic inclusions
• Clinically:
  
  • 5-7 day incubation after coming into contact with an infected animal
  • Painful papule evolves rapidly to become vesicular, pustular or haemorrhagic, may have umbilication
  • Most commonly on hands, arms or face. Can scar.
  • Can be widespread in eczema or immunosuppressed
  • Heals with scarring
• Ddx:
  
  • Other poxviruses: Orf, milker’s nodules
• Ix:
  
  • Serology - viral DNA
  • PCR
• Management:
  
  • None, self-resolving
  • manage bacterial infections

Question 8

Orf clinical

Answer 8

• Found in sheep and goats, have had human to human transmission
• Clinically:
  
  • Lesion develops 5-6 days after contact
  • reddish-blue papule appears at the skin site of contact and enlargens to a haemorrhagic pustule or bulla, usually ~ 3 cm
  • Often lymphadenitis and lymphangitis with a mild fever
  • Commonly on hands and forearms
  • Impaired immunity or eczema –> widespread lesions
  • 10% develop erythema multiforme, very rarely immunobullous
  • Takes 3-6 weeks to heal

Question 9

Orf investigations

Answer 9

• PCR of blister fluid
• Biopsy:
  
  • Epidermis shows ballooning degeneration of keratinocytes (photo) with eosinophilic cytoplasmic inclusion
  • Dense cellular infiltrate in dermis

Question 10

Orf treatment

Answer 10

• Not usually necessary
• Can excise large lesions
• Recurrent: trial cryotherpay, imiquimod, cidofovir, idoxuridine

Question 11

Rickettsiae - what are they and transmission

Answer 11

• Small obligate intracellular gram negative bacteria
• In arthropods

Transmission

• Lives in arthropods
• Arthropods bite human host —> saliva transmits bacteria
• In some cases it is in lice, which is then rubbed into skin

Question 12

Rickettsiae - pathogenesis

Answer 12

• It enters the dermis, and then attaches to erythrocytes
• It attaches to erythrocytes via the outer membrane protein A and B
• It then gets phagocytosed, and enters the cytosol where it utilises amino acids and nucleosides to undergo binary fission
• It then moves through the body through erythrocytes
• It causes vascular permeability
• It either replicates enough to eventually kill the host cell, or induces apoptosis
  Host response:
• TH1 response —> interferon gamma and TNF alpha
• Calls upon macrophages and lymphocytes —> cytotoxic T cells
• ROS, NO etc results in infected cell death
• Also cytokines activate infected cells resulting in death

Question 13

Rickettsiae clinical features

Answer 13

• Constitutional six: fever > 39 degrees, malaise
• GIT: nausea, vomiting, abdominal pain and tenderness
• Neurological - confusion secondary to encephalitis
• Resp - cough secondary to interstitial pneumonitis, pneumonia
• Haem - anaemia, DIC, thrombocytopaenia
• Ends - Hyponatraemia secondary to excessive ADH release
• Life threatening: vascular permeability leads to hypotensive shock —> ARF, ARDS, AMI, etc

Question 14

Rickettsiae - cutaneous features

Answer 14

• Echar from bite initially
• Rash 3-6 days later
• Starts as macular due to vascular permeability
• Then becomes papulewith oedema
• Then becomes petechiaedue to vascular damage, that coalesce to become purpura
• Cutaneous necrosis can also happen in acral sites, nose and ears —> likely because there is more of the bacteria here due to lower temperatures and micro circulation (necrosis only occurs in 4% of patients)

Question 15

Rickettsiae histology

Answer 15

• Classic is leukocytoclastic vasculitis with erythrocytes extravasation
• Echar will show coagulative necrosis

Question 16

Rickettsiae diagnosis

Answer 16

Retrospective serology - 4Xfold

Question 17

Rickettsiae treatment

Answer 17

• Doxcycline 100 mg BD

- Alternative: chloramphenicol

Question 18

Scrub typhus

Answer 18

• Occurs in northern australia and asia
• From chugger bites 60-90% of time
• Eschar
• Rash
• Lymphadenopathy, hearing loss
• Treat with doxycycline too

Question 19

Four bacterial phyla that cover majority of skin

Answer 19

• actinobacteria
• firmicutes
• bacteroidetes
• proteobacteria

Question 20

Impetigo epidemiology

Answer 20

• <6 years of age
• extremely contagious
• likes heat, hot weather, contact sports

Question 21

Impetigo pathogenesis

Answer 21

• Non-bullous: caused by Staph aureus, less commonly Strep pyogenes. Occurs at site of skin barrier compromise. This allows bacteria to adhere, invade and establish infection.
• Bullous: local production of exfoliative toxins A and B by phage group II of Staph aureus –> cleaves at desmoglein 1 resulting in acantholysis within the epidermal granular layer. Can be cultured from fluid.

Question 22

Non-bullous impetigo clinical

Answer 22

• Non-bullous
  
  • 70% of all cases
  • Single 2-4 mm macule that rapidly evolves into a short-lived vesicle/pustule
  • Late: superficial erosion, honey-coloured yellow crust
  • Face - around nose and mouth, and extremities
  • Mild lymphadenopathy
  • Usually benign, resolves within 2 weeks
  • Cx: 5% cases caused by strep pyogenes –> acute post-strep GN, this risk is not altered by antibiotics

Question 23

Bullous impetigo clinical

Answer 23

• Less common, often occurs in neonatal period
• Early: small vesicles that enlarge 1-2 cm in superficial bullae
• Late: flaccid, transparent measuring up to 5 cm in diameter, after ruputre there is a collarette of scale
• Usually on face, trunk, buttocks, perineum, axillae, extremities
• No systemic symptoms
• Resolves in 3-6 weeks
• If immunodeficient or renal failure –> risk of staph scalded skin

Question 24

Impetigo treatment

Answer 24

• Topicals: mupirocin, fusidic acid
• Cleansing the affected area and removing crusts
• If co-morbidities or large extent –> PO abx

Question 25

Bacterial folliculitis pathogenesis

Answer 25

• Staph aureus is the most common cause
• Can get gram negative in acne vulgaris
• Can get pseudomonal folliculitis from improperly chlorinated hot tubs and whirlpools
• Risk factors:
  
  • Occlusion, maceration, hyperhydratiion of the skin
  • Shaving, plucking, waxing
  • Topical steroids
  • Hot weather
  • Eczema
  • DM

Question 26

Bacterial folliculitis clinical

Answer 26

• Involves face, scalp, chest, back, axillae + buttocks
• Superficial = impetigo of Bockhart –> smaller pustules, clustered, heal without scarring
• Type of Deep = sycosis barbae –> large erythematous papules with a central pustule, may coalesce to form plaques
• Pruritic or tender

Question 27

Bacterial folliculitis treatment

Answer 27

• Antibacterial washes
• Topical abx - mupirocin or clindamycin for 7-10 days
• Wide - oral beta-lactam, tetracyclines, macrolides
• Pseudomonal - ciprofloxacin
• Recurrent:
  
  • mupirocin 2% ointment BD to nose for 5-10 days, topical antibacterial washes and dilue sodium hypochlorite baths
  • Elimination of bacterial contamination of potential fomites - ethanol or sodium hypochlorite based disinfectants

Question 28

Bacterial folliculitis ddx

Answer 28

• Other forms of folliculitis
• Acne, rosacea, chloracne
• Pseudofolliculitis barbae
• KP

Question 29

Blistering Distal dactylitis

Answer 29

• Localized infection of the volar fat pad of the finger or less commonly toe
• darkening of the skin for days-week then develop blister
• most commonly kids 2-16
• Cause; Group A strep or staph aureus
• follows local inoculation or autoinoculation
• Ddx: herpetic whitlow, thermal or chemical burn, acute paronychia, bullous impetigo, frictional bullae
• Rx: drainage + 10 day course of abx, can use topical mupirocin

Question 30

Abcesses, Furuncles and Carbuncles epi

Answer 30

• Abscesses and furuncles: walled off collections of pus
• Furuncle: involves a hair follicle
• Carbuncle: contiguous collection of furuncles
  Epidemiology and pathogenesis
• Adolescents and young adults
• Most common pathogen: staph auerus, occasionally can be anaerobic
• Risk factors: chronic Staph auerus carriage, close personal contact, diabetes, obesity, poor hygiene, immunodeificnecy syndromes, sensory and autonomic neuropathy

Question 31

Abcesses, Furuncles and Carbuncles clinical

Answer 31

• Abscess: localized collection of pus on any cutaneous site, sites prone to friction or minor trauma
• Furuncle: involves hair follicle - face, neck, axillae, buttocks, thighs. Firm, tender nodules that enlarge and become painful and fluctuant
• Systemic: lymphadenopathy, fever
• Carbuncle: collection of furuncles that extend into subcutaneous tissue, surface usually displays multiple draining sinus tracts and occasionally ulcerates. Occur in areas where there is thicker skin. Systemic often present

Question 32

Abcesses, Furuncles and Carbuncles treatment

Answer 32

• Simple furuncles
  
  • warm compress may promote maturation, drainage and resolution
• Larger/deeper furuncle
  
  • incision and drainage
• When for antibiotics:
  
  • furuncles around the nose, external auditory canal, other areas where drainage is difficult
  • Severe or extensive disease
  • Lesions with surrounding ceullitis or phlebitis
  • Not responding to local care
  • Comorbidities ++
• Antibiotics: empirically cover with doxycycline, TMP-SMX or clindamycin
• evidence that after incision and drainage giving antibiotics improves cure rate and reduces recurrence rate

Question 33

MRSA Pathogenesis and resistance

Answer 33

• methicillin resistance: produce penicillin binding protein 2a (PBP2a) that has decreased affinity for beta lactam antibiotics
• PBP2a is the protein product of mecA gene
• HA-MRSA and CA-MRSA are the acquisition of SCC mec elements
• CA-MRSA also have other virulence factors such as Panton-Valentine leukocidin - a pore forming cytotoxin that can cause destruction of leukocytes and tissue necrosis
• CA-MRSA typically susceptible to multiple non-beta lactam antibiotics
• HA-MRSA resistant to more - including aminoglycosides, macrolides and clindamycin

Question 34

How staph aureus develops resistance to macrolides

Answer 34

• 1. active drug efflux via a pump encoded by the msrA/msrB gene
• 2. synthesis of macrolide-inactivating enzymes
• 3. modification of the bacterial ribosome by the erythromycin ribosomal methylase encoded by erm genes - produces cross resistance to clindamycin
     If initial sensitivity testing shows resistance to erythromycin and susceptiblity to clindamycin, resistance to clinda will develop if erm is present. Can test this with the D test

Question 35

MRSA treatment

Answer 35

• Severe infection of MRSA: use vancomycin

Question 36

Echthyma

Answer 36

• deep form of non-bullous impetigo –> extension into the dermis to produce a shallow ulcer that heals with scarring
• Cause by strep pyogenes
• Occurs among infantry units where skin trauma, poor hygiene, crowded living
• Clinically:
  
  • fewer than ten lesions, commonly on extremities
  • vesiculopustule enlarges and develops a haemorrhagic crust
  • ulcer has punched out appearance and a purulent necrotic base
  • slow to heal
• Ddx: echthyma gangrenosum, ulcers due to vasculitis, vasculopathies
• Rx: abx

Question 37

SSSS Epidemiology

Answer 37

• primarily infants and young children
• can happen in adults with renal failure or immnuosuppression
• outbreaks: neonatal nurseries when someone has an asymptomatic carriage of toxigenic strain of staph aureus by healthcare workers or parents
• M:F 2:1

Question 38

SSSS pathogenesis

Answer 38

• Staph aureus phage group 2 strains produce exfoliative/epidermolytic toxins ETA and ETC that are serine proteases that bind and cleave desmoglein 1
• this causes splitting of the desmosomes and disruption of the epidermal granular layer and bulla formation
• Toxin spread haematogenously to produce a widespread effect
• Kids - infection focus often the nasopharynx or conjunctivae, where as for adults often pneumonia or bacteraemia

Question 39

SSSS Clinical

Answer 39

• Prodrome: malaise, fever, irritability, tenderness, rhinorrhoea or conjunctivitis
• Erythema first appears on the head and in intertriginous sites, generalized by 48 hours
• Develops wrinkled appearance due to flaccid, sterile bullae
• Nikolsky positive
• Flexural areas first to exfoliate
• Peri-oroficial crusting and radial fissuring
• No intra-oral involvement
• Scaling over next 3-5 days, following by re-epithelialization over 1-2 weeks
• Mortality <4% kids, 60% adults

Question 40

SSSS histo

Answer 40

• Sharply demarcated zone of cleavage at or below the stratum granulosum
• no inflammatory cells
• no organisms seen

Question 41

SSSS ddx

Answer 41

• Drug
• Viral
• Kawasaki
• Extensive bullous impetigo
• Toxic shock
• GVHD
• TEN
• Pemphigus foliaecus

Question 42

SSSS Rx

Answer 42

• Hospitalization
• Beta lactamase resistant antibiotics for a minimum of 1 week orally in minor cases, IV in severe
• Clindamycin may help reduce bacterial toxin prodictuion, but up to 50% of strains are resistant
• Decolonize staph carriage

Question 43

Staph toxic shock epi and pathogenesis

Answer 43

• Used to be from tampons
• Now from: surgical procedures, cutaneous pyodermas, post partum, abscesses, burns, infections associated with nasal packing or insulin pump infusion sites
• Due to infection or colonization with strains of staph auerues that produce toxic shock syndrome toxin-1 (TSST-1)
• this acts as a superantigen that binds to MHC class 2 molecules of APCs and on T cell receptors –> leads to massive cytokine release and clonal T cell expansion
• Basically a cytokine storm
• Neonatal TSS like exanthematous diease occurs during the first week of like due to colonization –> relatively milder course

Question 44

Staph toxic shock clinical

Answer 44

• High fever, myalgia, vomiting, diarrhoea, headache, pharyngitis –> hypotensive shock
• Diffuse erythema or scarlatiniform examthen - starts on trunk and spreads to extremities
• Erythema and oedema of the palms, soles and oral mucosa
• Strawberry tongue, hyperaemia of the conjunctivate
• Generalized non-pitting oedema
• Desquamation 1-3 weeks after
• Nails: Beau’s lines and nail shedding
• Hair: tolgen effluvium
• Complications: renail failure, prolonged weakness and fatigue, myalgia, vocal cord paralysis, upper extremity paraesthesias, carpal tunnel syndrome, arthralgias, amenorrhoea, grangrene

Question 45

Staph toxic shock case definition

Answer 45

• Fever + diffuse macular rash + desquamtion + hypotension
• 3 or more ogran involvement
• Negative cultures

Question 46

Staph toxic shock histo

Answer 46

• Neutrophilic and lymphocytic infiltrate in the superficial dermis
• Papillary dermal oedema and spongiosis

Question 47

Staph toxic shock ddx

Answer 47

• Strep TSS
• Kawasaki
• Scarlet fever
• SSSS
• TEN
• Rocky mountain spotted fever
• leptospirosis

Question 48

Staph toxic shock rx

Answer 48

• Intensive monitoring and supportive therapy
• Foreign body removal
• Beta-lactamase resistant abx
• MRSA only responsible for small portion
• Clinda? may suppress protein production
• IVIF - neutralized toxin

Question 49

Scarlet fever epi and path

Answer 49

• Caused by strep pyrogenic exotxins types A, B and C - produced by group A strep
• 1- 10 years of age
• 80% of the population has developed anti-SPE antibodies by the age of 10
• Usually follows tonsillitis or pharyngitis, or can be from complication of a wound

Question 50

Scarlet fever clinical

Answer 50

• Sore throat, headache, malaise, chills, anorexia, nausea, fevers
• +/- abdominal pain, vomiting, seizures
• 12-48 hours later: blanchable erythema on the neck, chest and axillae –> then generalized with tiny superimposed papules with a sandpaper like texture
• Pastia’s line: linear petechial streaks in the axillary, antecubital and inguinal area
• Throat red, oedematous and exudate with palatal petechiae and tender cervical adenopathy
• Tongue initially white, then becomes bright red papillae –> then beefy red strawberry tongue
• Desquamation can last 2-6 weeks
• Complications: otitis, mastoiditis, sinusitis, pneumonia, myocarditis, meningitis, arthritis, hepatitis, acute GN and rheumatic fever

Question 51

Scarlet fever histo

Answer 51

• Engorged capillaries and dilated lymphatics, particularly around hair follicles
• Dermal oedema, perivascular neutrophilic infiltates
• Spongiosis and parakeratosis

Question 52

Scarlet fever ix

Answer 52

• leukocytosis
• eosinophilia
• haemolytic anaemia
• mild albuminuria and haematuria
• nasal and or throat cultures grow
• ASOT and anti-DNAase B antibodies

Question 53

Scarlet fever treatment

Answer 53

• Penicillin 10-14 days, usually have clinical response within 24-48 hours
• give for 10 days to prevent rheumatic fever
• if allergy: first gen cephalosporin

Question 54

Scarlet fever ddx

Answer 54

• Drug
• viral
• TSS
• early SSSS
• Kawasaki
• Arcanobacterium haemolyticum - can cause pharyngitis and scarlatiniform exanthem

Question 55

Strep toxic shock epi and path

Answer 55

• healthy 20-50 year olds
• disruption of cutaneous barrier –> portal of entry
• associated with invasive sot tissue infections with virulent strains of group A strep
• Toxins implicated: SPE A, B and C and SMEZ
• Streptolysin O may act synergistically with SPE-A
• Results in massive cytokine release due to superantigen activity of bacterial exotoxins
• Activation of up to 30% of entire circulating T cell population
• TNF alpha, IL-1 and IL-6
• Fever, erythematous eruptions, vomiting, hypotension, tissue injury
• NSAIDs may delay diagnosis

Question 56

Strep toxic shock clinical

Answer 56

• GAS
• Most common initial symptom: local pain in extremity
• Development of violaceous hue, bullae or necrosis points to deeper infection
• Non-specific flu like symptoms
• CNS - confusion
• Generalised blanching macular erythema, blistering more likely
• Palmoplantar desquamation in 20%
• Mutli-rogan failure in 48-72 hours
• Cx: renal failure, DIC, ARDS

Question 57

Strep toxic shock histo

Answer 57

• Spongiosis
• Necrotic keratinocytes
• Subepidermal blister formation
• Neutrophilic and lymphocytic perivascular infiltrate

Question 58

Strep toxic shock case definition

Answer 58

1. Isolated group A strep from normally sterile site or from a non sterile site
2. Hypotension
3. 2 ore more following signs of organ involvement

Question 59

Strep toxic shock ix

Answer 59

• Elevated CK and serum creatinine early

- Leukocytosis

Question 60

Strep toxic shock mgmt

Answer 60

• intensive supportive therapy
• Clindamycin - inhibits bacterial toxins, as does linelozid
• IVIG to neutralize antibodies may be of benefit
• Early surgical intervention for soft tissue infections

Question 61

Peianal and vulvovagnial strep infection (perineal strep infection)

Answer 61

• sharply demarcated bright erythema extending 1-3 cm around the anal verge, can include vaginal introitus
• pruritis, dysuria, painful defecation, blood streaked stools
• no systemic involvement usually
• usually young boys 2-7 years
• associated with positive pharyngeal culture
• ddx: contact dermatitis, staph, candida, seb derm, pinwrom, IBD, LS, child abuse, early Kawasaki
• Rx: 7 day course of cefuroxime, or can do 10 day penicillin but less effective

Question 62

Cellulitis epi and path

Answer 62

• Immunocompetent –> Staph and strep, not haemophilus influenze anymore due to vaccine
• immunuosuppressed ie diabetic: mixed
• Bacteria gain access in skin barrier break, immunocompromised can be haematogenous
• Risk factors: alcoholism, lymphoedema, DM, IDU, PVD

Question 63

Cellulitis clinical

Answer 63

• Systemic symptoms: fever, chills, malaise
• Erythema, pain, swelling, heat
• ill-defined borders and non-palpable
• severe: vesicles, bullae, pustules, necrotic tissue
• Children: head and neck
• Complications: acute GN, lymphadenitis, subacute bacterial endocarditis, recurrence if lymphatic damage

Question 64

Cellulitis histo

Answer 64

• Lymphocytes and neutrophils into subcutaneous fat

- Oedema, subepidermal bullae, lymphatic and BV dilation

Question 65

Cellulitis treatment

Answer 65

• Target against GAS and staph
• Uncomplicated: 10 days oral antibiotics
• Severe IV abx and hospitalization, if MRSA suspected –> clinda, doxy or TMP-SMX
• Diabetic: braod cover
• Adjunctive: immobilization, elevation, application fo wet dressings
• If no improvement after 36-48 hours need to re-investigate
• Don’t give NSAIDs - mask signs of deep necrotizing infections
• Recurrent: low dose prophylactic penicillin, but stops working as soon as stop taking

Question 66

Pyomyositis

Answer 66

• primary bacterial infection of the skeletal muscles
• most commonly: staph aureus
• Other: strep pyogenes, strep pneumoniae, E coli, Yersinia, h influenzae
• temperate climates
• Risk factors: trauma, diabetes, HIV, IDU, immunosuppressed
• 1-2 week history of low grade fevers, myalgias, firmness, pain, enlargement of deep soft tissue mass
• become ‘woody’ –> develop muscle abscess
• Ix: MRI
• Rx: incision and drainage, IV abx and then followed by PO therapy for at least 3 weeks

Question 67

Botromycosis Epi and Path

Answer 67

• worldwide
• males>females
• staph, pseudomonas, proteus, moraxella, serratia, corynebacteria
• associated with impaired immunity

Question 68

Botromycosis clinical

Answer 68

• deeper so cutaneous and subcutaneous nodules, ulcers, verrucous plaques
• sinuses and distulas with yellow discharge
• pruritic or tender, may affect the underlying muscle or bone
• can get visceral botromycosis - lungs

Question 69

Botromycosis histo

Answer 69

• chronic inflammatory reaction with fibrosis and foreign body giant cells
• Granular bodies: bacteria, cells and debris. Have basophilic centres and homogenous, eosinophilic, hyaline periphery thought to be secondary to a host ommunoglobulin response
• Stains PAS, gram and Giemsa
• Microscopic exam: coarsely lobulated granules with club like projections

Question 70

Botromycosis ddx

Answer 70

• Mycetoma
• Actinomycosis
• Ruptured epidermoid cyst
• Staph abscess
• Orf
• TB
• Dimorphic fungal or atypical mycobacterial infections

Question 71

Botromycosis rx

Answer 71

• Surgical debridement or excision

- Ablation with CO2 laser

Question 72

Necrotizing fasciitis epidemiology and pathogenesis

Answer 72

• Risk factors: DM, immunosuppressed, cardiac or PVD, renal failure, bevacizumab therapy
• Follows trauma sometimes but not always, otherwise IDU, recent surgery, varicella, ulcers
• Mortality 20-60%
• Poor prognostic factors:
  
  • Female
  • older age
  • Malnutrition
  • Delay to first debridement
  • Elevated serum creatinine or lactic acid
  • Disease due to GAS
  • Greater degree of organ dysfunction at time of hospital admission
• Kids: GAS
• Adults: polymicrobial:
  
  • Staph, strep, e coli, bacteroides, clostridium
  • Uncommon: V vulnificus (sea water), Aeromonas hydrophila (fresh water), pseudomonas Hib
  • Opportunistic fungal such as zygomycosis in immunosuppressed

Question 73

Necrotizing fasciitis clinical

Answer 73

• ++ Tender
• Erythema, warmth, swelling
• Recalcitrant to abx
• Skin: shiny and tense
• Initially skin pain out of proportion to findings
• Progresses quickly: red-purple to grey-blue, with violaceous haemorrhagic bullae superimposed
• Necrosis of the superficial fascia and fat produces a thing, watery malodorous fluid
• Anaesthesia as cutaneous nerves are destroyed
• Subcut tissue becomes hard and ‘woody’
• Systemic: fever, tachycardia, shock
• Common site: extremities, trunk for kids
• Fournier grangrene: perineum and genitalia, usually polymicrobial

Question 74

Necrotizing fasciitis pathology

Answer 74

• Gangrene of the subcutaneous tissue, spreading along fascial planes
• Fibrinoid necrosis in the media of vessels, fibrin thrombi
• Everything undergoes coagulation necrosis
• Neutrophils and mononuclear cells

Question 75

Necrotizing fasciitis ddx

Answer 75

• MRI but that can delay management

- Ddx: trauma with haematoma, clostridial myonecrosis, pyomyositis, phlebitis, bursitis, arthritis

Question 76

Necrotizing fasciitis Rx

Answer 76

• Fasciotomy: mainstay, may have to amputate
• Empiric therapy: vanc, linezolid, daptomycin, tazocin, carbapenem
• If true penicillin allergy: cipro + metro
• If neutropenic: cover pseudomonas
• Hyperbaric oxygen is controversial
• No evidence fo IVIG
• Give nutritional support

Question 77

Clostridia

Answer 77

• spore-forming gram positive rods
• found in soil and normal intestinal flora
• Clostridium perfringens is the most frequent cause of trauma associated gas gangrene - obligate anaerobe, so proliferates in ischaemic tissue
  
  • Produces 2 toxins:
    
    • Alpha
    • Theta- disrupts endothelial cell tissue integrity
  • basically causes ischaemia
  • pdn of hydrogen sulfide and co2 results in the gas production
• Clostridium septicum - aerotolerant, requires smaller infective dose, associated with spontaneous gas gangrene in neutropenic and GI malignancy

Question 78

Myonecrosis and anaerobic cellulitis

Answer 78

• usually from trauma
• Myonecrosis more rapid
• Have thing, dark gray-brown foul smelling ‘dirty dishwater’
• minimal overlying skin changes
• can have crepitus
• severe pain in myonecrosis
• need early surgical debridement
• cover broad spectrum

Question 79

Erythrasma

Answer 79

• superficial and chronic
• From excessive proliferation of Corynebacterium within the stratum corneum
• Favour moist, occluded intertriginous areas including the groin, axillae, web spaces in the toes
• Risk factors: humid, poor hygiene, hyperhidrosis, obesity, diabetes, advanced age, immunosuppression
• Pink-red well-defined patches that are covered with fine scale. eventually fades and turns to brown
• Can have disciform - more widespread
• Interdigital most common - macerated between toes
• Wood’s lamp: bright coral red fluorescence due to the porphyrin released by the bacteria
• Gram stain: filament s and rods
• Culture on Tissue Culture Medium 199
• Ddx: tinea, seb derm, candidiasis
• Rx: 20% aluminium chloride, clinda, erythro, fudisic, mupirocin, azoles, Whitfields. Oral erythro or tetra or single dose clarithromycin if widespread

Question 80

Pitted keratolysis epi and path

Answer 80

• Temperate and tropical climates
• RF: hyperhidrosis, prolonged occlusion, increased skin surface pH
• Caused by Kytococcus sedentarius, others can be cornyebacteria and actinomyces
• Kytococcus produces 2 serine proteases that degrade keratin in the stratum corneum

Question 81

Pitted keratolysis clinical

Answer 81

• small crater like depressions are present within the stratum corneum - weight bearing in particular
• can coalesce into large craters or rings
• no erythema
• No fluorescence on woods lamp

Question 82

Pitted keratolysis histo

Answer 82

• pits 2/3 way into stratum corneum

- Gram, PAS and Gomori methenamine silver stains reveal bacteria

Question 83

Pitted keratolysis ddx

Answer 83

• Plantar warts
• Tinea
• Palmoplantar punctate keratoderma
• Basal cell naevus syndrome
• Dariers
• Palmoplantar hypokeratosis

Question 84

Pitted keratolysis Rx

Answer 84

• Benzyl peroxide, erythromycin, clinda, mupirocin, tetracycline
• Aluminium chloride 20% in recalcitrant cases

Question 85

Clostridial skin infections

Answer 85

• spore-forming gram positive rods
• found in soil and normal intestinal flora
• Clostridium perfringens is the most frequent cause of trauma associated gas gangrene - obligate anaerobe, so proliferates in ischaemic tissue
  
  • Produces 2 toxins:
    
    • Alpha
    • Theta- disrupts endothelial cell tissue integrity
  • basically causes ischaemia
  • pdn of hydrogen sulfide and co2 results in the gas production
• Clostridium septicum - aerotolerant, requires smaller infective dose, associated with spontaneous gas gangrene in neutropenic and GI malignancy
• Myonecrosis and anaerobic cellulitis are both caused by clostridia:
  
  • usually from trauma
  • Myonecrosis more rapid
  • Have thing, dark gray-brown foul smelling ‘dirty dishwater’
  • minimal overlying skin changes
  • can have crepitus
  • severe pain in myonecrosis
  • need early surgical debridement
  • cover broad spectrum

Question 86

Trichomycosis axillaris, pubic and capitis

Answer 86

• Superficial cornyebacteria - trichomycosis –> concretions of the shaft
• develops adherent yellow, red or black nodules
• Dermatoscope: flame like concretions
• Odour
• Sweat –> red colour
• Woods lamp: yellow
• Rx: shave, or antimicrobial cleansers

Question 87

Cutaneous diptheria

Answer 87

• Cause: toxigenic and non-toxigenic Cornyebacteirum diphtheriae and ulcerans
• Endemic to tropical countries
• Spread: person to person –> very contagious
• Ulcerans: domestic animals too
• Cutaneous: form of immunization –> slowly absorbed and develop antibodies
• Risk factors: poor hygiene, skin trauma, IDU
• Clinical: ulcer with a punched out appearnce and pseudomembranous eschar
• Acral sites are favoured
• Complications: myocarditis, polyneuritis - rare
• Diagnose: gram stain, to test toxigenicity can do PCR or Elek immunoprecipitation test
• Rx: PO erythromycin or penicillin for 10 days, clean wound, topical antibiotic and IV antibiotics if toxic, screen contacts

Question 88

Cutaneous anthrax cause

Answer 88

• Bacillus anthracis - aerobic, sporulating, gram positive rod
• Inhale, ingest or inoculate
• Disease of animals, endemic to western Asia and Africa
• The spores are hardy and can last for ages
• full virulence - antiphagocytic capsule and 3 toxin components –> lethal toxin and oedema toxin

Question 89

Cutaneous anthrax clinical

Answer 89

• Incubate 1-12 days
• Purpuric macule or papule in exposed area, may resemble an insect bite –> then vesicle forms with non-pitting oedema, then it ulcerates
• Lesion become haemorrhagic and depressed –> painless black necrotic eschar forms centrally with an increase in the surrounding erythema and oedema
• Then dries, loosens and sloughs over the next 1-2 weeks with no permanent scar
• Rarely lymphangitis and painful lymphadenopathy
• Antibiotics don’t alter the progression as its toxin mediated

Question 90

Cutaneous anthrax path

Answer 90

• Spongiosis, papillary dermal oedema
• Superficial and deem inflam infiltrate with neutrophils
• Substantial haemorrhage
• Elongated gram positive bacilli - in small clusters. Grows readily on culture media at 37 degrees with a jointed bamboo rod cellular appearance and a unique curled hair colonial morphology

Question 91

Cutaneous anthrax dx and ddx

Answer 91

• Gram stain –> rapid diagnosis. Grows within 6-24 hours
• Lab must make sure its not B cereus –> need to do lethal factor, CPR, etc
• Ddx:
  
  • Brown recluse spider bite
  • Rickettsia
  • Cellulitis
  • Echthyma gangrenosum
  • Orf
  • Milker’s nodule
  • Opportunistic bacterial and fungal infections

Question 92

Cutaneous anthrax treatment

Answer 92

• Without treatment, mortality can be up to 20%
• If inhaled as well - antibiotics for at leat 60 days
• Quinolones (cipro etc) and doxy are first line agents, with clinda an alternative
• Post-exposure vaccine: 0, 1 , 6, 12 and 18 months

Question 93

Bacilus cereus

Answer 93

• Causes mild food poisoining
• Can get single necrotic bulla
• When immunosuppressed can be quite bad with meninigitis etc
• Rx: vanc

Question 94

Erysipiloid

Answer 94

• Erysipelothrix - gram positive, non-motile bacillus
• traumatic inoculation - fishermen (meat, poultry, fish)
• Localized form: erythematous to violaceous non-suppurative cellulitis - pruritis or painful
• Generalised: feers and arthralgias - perifollicular papules to erythematous plaques, macular purpura and necrosis
• Cx: endocarditis, septic arthritis, cerebral and other visceral abscesses
• Difficult to culture
• Rx: goes away spontaneously, penicillin, erythromycin, cephalosporins, clinda, etc

Question 95

Neisseria epidemiology

Answer 95

• Primarily infants, adolescents and young adults
• M>F 3-4:1
• Develop winter and spring
• Increased risk: asplenia, complement deficiency (may be associated with partial lipodystrophy), low immunoglobulins, complement inhibitor eculizumab
• Also at risk: low TNF alpha, high IL-10, plasminogen activator inhibitor 1, alleles on IL-1

Question 96

Neisseria pathogenesis

Answer 96

• Neisseria:
  
  • polysaccharide capsule
  • at least 13 strains
• proliferates in host cell - produces bacterial transferase that modifies the type IV pilli –> results in bacterial detachment and migration across the epithelium
• endotoxin released - triggers inflammatory response resulting in shock, multi-organ failure and purpura fulminans
• Reservoir: human nasopharynx. Asymptomatic carriage 5-15%
• Disruption of respiratory mucosa: viral infection, smoking –> increase risk of invasive meningococcal disease

Question 97

Neisseria clinical

Answer 97

• Most commonly: asymptomatic carrier state –> lifelong immunity
• Upper respiratory symptoms as well as bacteraemia, without sepsis
• Acute:
  
  • 1/3 to 1/2 present with petechial eruption –> fevers, chills, myalgias, headache
  • Then becomes retiform purpura (gunmetal grey) and ischaemic necrosis
  • Occasionally bullous haemorrhagic lesions, most commonly on the trunk and lower extremities
  • Minority of patients: transient, blanchable morbilliform eruption
  • Hypotension, meningitis, meningoencephalitis, pneumonia, arthritis, pericarditis, myocarditis, DIC
• Chronic:
  
  • Rare
  • recurrent fever, arthralgia, polymorphous erythematous macules and papules 12-24 hours after fever onset
  • lesions may develop into tender nodules with indistinct borders
  • petechiae, retiform purpura, pustules, EMA
  • tend to resolve concurrently with fever within 2-10 days

Question 98

Neisseria histo

Answer 98

• Leukocytoclastic vasculitis and thrombosis
• Gram stain positive in 70% cases
• Chronic: perivascular infiltrate of lymphocytes and a few neutrophils can be appreciated, and LCV may be seen in petechial lesions

Question 99

Neisseria diagnosis

Answer 99

• Clinical initially –> need to manage quickly as can deteriorate
• Culture of N meningitidis from skin or normally sterile bodily fluid
• CSF and urine latex agglutination for groups A, B, C, Y and W1-35 antigens - good specificity but low sensitivity
• PCR - specific with better sensitivity
• Gram stain - gram negative diplococci

Question 100

Neisseria differentials

Answer 100

• Enterovirall infections
• Rocky Mountain spotted fever
• Septic vasculitis
• TSS
• Purpura fulminans
• Leptospirosis
• Vasculitis
• Chronic:
  
  • Bacterial endocarditis
  • Sweets
  • HSP
  • Rat bite fever
  • EM
  • Chronic gonococcaemia

Question 101

Neisseria treatment

Answer 101

• Try and get cultures before antibiotics
• Third generation cephalosporin - ceftriaxone initially, then can switch to penicillin once confirmed and susceptible, or chloramphenicol and quinolones with penicillin hypersensitivity
• Development of ciprofloxacin resistant strains
• Close contacts –> prophylactic treatment
• Vaccines: three quadrivalen vaccines against A, C, W and Y, and a bivalent vaccine against C and Y plus HiB
  
  • duration of immunity is 3-5 years
  • quadrivalent conjugated given at age 11-12, and then booster at 16
  • also administered to high risk: college students in dorms, military recruits, or those at risk >2 months of age
  • Monovalent serogroup B is recommended for patients >10 years in the high risk group

Question 102

Pseudomonas info

Answer 102

• Gram negative, strictly aerobic, motile bacillus
• Widely distributed: soil, plants, aqueous environments
• Low virulence, usually requires a local anatomic or immunologic defect to cause disease

Question 103

Green nail syndrome

Answer 103

• Called chloronychia
• pseudomonas
• Pyocyanin results in green-black-blue discolouration (oxidises and reduces other molecules)
• Predisposing factors: frequent or prolonged exposure to water, excessive detergent and soap use, nail trauma, other causes of onycholysis
• Gram stain and culture of exudate and nail fragments results in diagnosis
• Ddx: subungual haematoma, melanocytic naevus, melanoma, Aspergillus
• Treatment: clipping the nail, 2% sodium hypochlorite, quinolone, aminoglycoside (tobramycin)
• If refractory: may need to remove the nail

Question 104

Pseudomonal Pyoderma and Blastomycosis-like Pyoderma

Answer 104

• Superficial infection
• Blue-green purulence, ‘grape juice like’or ‘mousy’odour, moth eaten appearance of the skin
• Borders are macerated and eroded
• Can complicate burns, decubitus ulcers, chronic cutaneous ulcers
• Can involve toe web infections and ínfectious eczematoid dermatitis
• Blastomycosis like: super rare, large verrucous plaques with multiple pustules and elevated borders –> pseudoepitheliomatous hyperplasia with intraepidermal abscesses, fungi are not seen. Usually immunocompromised
• Rx: systemic antipseudomonal antibiotics, topical antimicrobials, drying agents, debridement of the hyperkeratotic rim in web space infections
• Additional treatments: acitretin, surgical excision, C&C, ablative laser

Question 105

Otitis Externa and Malignant Otitis Externa

Answer 105

• P aeruginosa colonizes 1-2% of normal ear canals
• Swimmer’s ear: acute infection, external auditory canal is swollen and macerated with a green, purulent discharge, manipulation of pinna ++ painful
• Rx: remove canal debris, antibiotic ear drops (cover S aureus co-infection)
• Malignant otitis externa: severe variant in diabetics or immunosuppressed –> severe pain, drainage, granulation tissue at junction of osseous and cartilaginous portions of the auditory canal. Deeper invasion can result in osteomyelitis etc
• Rx: IV penicillin or cephalosporin + oral ciprofloxacin +/- surgical intervention

Question 106

Pseudomonal folliculitis

Answer 106

• Hot tub folliculitis
• Whirlpools, hot tubs and swimming pools with low chlorine levels
• Erythematous, oedematous perifollicular papules and papulopustules arise 8-48 hours after exposure
• resolve spontaneously 7-14 days later
• sites covered by bathing suits, spares the face and neck
• associated symptoms: pruritis, painful eyes, earaches, sore throat, headache, fever, painful swollen breasts, rhinorrhoea, GIT upset
• Dx: isolation of P aeruginosa - particularly O-11
• Ddx: other forms of folliculitis and papular urticaria
• Rx: not needed in immunocompetent, warm compresses with 2% acetic acid, topical gentamicin, if immunosuppressed –> oral quinolone

Question 107

Pseudomonas hot foot syndrome

Answer 107

• occurs after swimming or wading in pool water that contains high concentrations of p aeruginosa
• soles: diffusely erythematous and painful, red to purple, 1-2 cm nodules, occasional palmar involvement
• rare systemic symptoms
• Histo: perivascular and peri-eccinre neutrophilic infiltrates with microabscess formation
• Self-limiting
• Other ddx: Idiopathic palmoplantar hidradenitis, pernio, symmetric lividities, EN

Question 108

Ecthyma gangrenosum

Answer 108

• Pseudomonas septicaemia in immunocompromised, particularly those with neutropenia (makes sense)
• Fever, hypotension, alterations in consciousness
• Occasional manifestation: ecthyma gangrenosum –> few in number, begin as erythematous or purpuric macules, most commonly located in the anogenital area or on the extremities –> then evolve into haemorrhagic vesicles or bullae which rupture and become necrotic ulcers with a black eschar
• Localized anogenital form in immunocompromised
• Histo: necrotizing haemorrhagic vasculitis, with gram negative rods in medial and adventitial walls, the intima is spared
• Rx: IV aminoglycoside + antipseudomonal penicillin
• Ddx: septic emboli from other organisms and saprophytic fungi, disseminated HSV may have similar appearance

Question 109

Lyme disease incidence and transmission

Answer 109

• Found worldwide, particularly high incidence in North America and Europe
• Can occur year round, but often present in the summer
• Vector: Ixodes tick vector
• Once the spirochete is in the midgut of the tick vector on an infected host, it produces outer surface protein, which enables it to traverse the midgut epithelium, enter the hemocel and make its way to the salivary glands
• Transmitted to humans via the tick’s saliva
• Rate of transmission is very low during the first 48 hours

Question 110

Lyme disease clinical

Answer 110

• Extra-cutaneous:
  
  • Constitutional - fever, cough, etc
  • Eyes: conjunctivities, keratitis, iritis, etc
  • Neuro: meningitis, GBS, Bells palsy, etc
  • Cardiac: heart block, arrhythmias
  • Rheum: arthralgias, tendinitis, etc
  • Genitourinary: orchitis

Question 111

Borrelial lymphocytoma clinical

Answer 111

• Usually appears during the early disseminated stage of Lyme disease
• Virtually never seen in those who have not travelled outside of the US
• Clinical: firm, bluish-red occasionally tender nodule or plaque appears most commonly on the earlobes in children, and the nipple/areola in adults

Question 112

Borrelial lymphocytoma histo and ddx

Answer 112

• Histo: normal epidermis, Grenz zone, dense dermal infiltrate of lymphocytes that closely resemble architecture of a lymphoid follicle
• Histo ddx: arthropod bite, cutaneous lymphoma (later presence of Bcl-2 protein within follicular cells and monoclonality by PCR favouring the latter)
• Very rare!

Question 113

Acrodermatitis chronica atrophicans epidemiology

Answer 113

• Common in Europe

- 6 months - 8 years after initial infection, women in 40s-70s –> associated with long-term persistence

Question 114

Acrodermatitis chronica atrophicans clinical

Answer 114

• Biphasic: early treatable inflammatory stage and a late, treatment-resistant atrophic stage
• Initially erythematous to violaceous plaques and nodules develop on the acral portion of the extremities, often insidious
• Skin feels soft and doughy. can lat for ages
• Late stage: skin is glistening (cigarette paper) with prominent blood vessels, +/- fibrous nodules on the extensor surfaces
• Hypopigmentation, hyperpigmentation, pain, pruritis, etc
• Rarely: BCC or SCC

Question 115

Acrodermatitis chronica atrophicans histo

Answer 115

• Histo: dermal perivascular lymphocytic infiltrate with plasma cells, telangiectatic endothelial lined spaces, mild epidermal atrophy
• Histo late: insterstitial lymphocytic infiltrate with palsma cells and occasional histiocytes and mast cells

Question 116

Acrodermatitis chronica atrophicans ddx

Answer 116

eczema, cold injury, atrophy secondary to chronic steroid use, severe photodamage, morphoea, fibromatoses

Question 117

Non-venereal treponematoses background - dx and rx

Answer 117

• Treponema pallidum - morphologically and antigenically identical to the causative organism of venereal syphilis
• Rout of transmission: person to person via skin, mucous membrane and fomite
• Diagnosis based primarily on clinical features
• Same serologic assays can be used to diagnose, but positive test doesn’t differentiate the diseases
• Treponemal: specific, and may remain positive for life
• Non-treponemal: current or recent infection, or biologic false-positive result. these are helpful for people following therapy to make sure there is successful treatment
• First line treatment is now azithromycin - single, high dose

Question 118

Yaws epi

Answer 118

• AKA Buba
• Caused by treponema pallidum
• Three stage infection: most common severe endemic treponematosis
• Warm, humid, tropical climates
• Clinical:
  
  • lower extremities of children <15 years of age

Question 119

Yaws clinical stages

Answer 119

1. Mother yaw
   
   • ‘Mother yaw’ is the main lesion (primary stage) - site of inoculation within 10 days - 3 months
   • becomes erythematous, infiltrated, painless papule that over time enlargens peripherally to become 1-5 cm in diameter, then uclerates and develops an amber-yellow crust
   • rich in treponemes
   • heals spontaneously over 3-6 months
2. Daughter yaw
   - smaller, more widespread
   - occur adjacent to the body orifices such as the nose and mouth, and can expand or uclerate
   - both types are ++ infectious
3. Final stage
   
   • 10% arrive here
   • abscesses, necrosis, ulcers
   • ulcers coalesce into serpiginous tracts –> heal with scarring and deformities
   • complications: periostitis, dactylitis, osteitis

Question 120

Yaws histo

Answer 120

• Early: spongiosis, acanthosis, papillomatosis, mod-dense dermal inflam infiltrate of plasma cells and lymphocytes
• Silver stain: treponemes

Question 121

Yaws ddx

Answer 121

• Syphilis
• Eczema
• Psoriasis
• Verrucae
• Calluses
• Scabies
• Tungiasis
• Sarcoidosis
• Vitamin deficiencies

Question 122

Pinta cause and epi

Answer 122

• Caused by T. carateum
• Affects skin exclusively
• In western hemisphere and warm climates

Question 123

Pinta clinical stages

Answer 123

• Primary lesion:
  
  • 7 days - 2 months after inoculation, on the lower extremities
  • Begin as tiny macules or papules surrounded by an erythematous halo
  • then over months develop into poorly defined, erythematous infiltrated plaques 10-12 cm in diameter
• Secondary lesions:
  
  • small, scaly papules that subsequently enlarge and coalesce into psoriasiform plaques
• Tertiary: symmetrical, depigmented vitiligo like lesions

Question 124

Pinta histology

Answer 124

• Moderate acanthosis, slight spongiosis, superficial dermal inflammatory infiltrate: lymphocytes, plasma cells, neutrophils
• Lichenoid changes, hyperkeratosis, hypergranulosis
• Late: epidermal atrophy and complete absence of melanin
• Silver strain: treponemes (not in really late stage)

Question 125

Pinta ddx

Answer 125

• Syphilis
• Eczema, psoriasis
• Leprosy
• LP
• Lupus
• Tinea
• Vitiligo

Question 126

Endemic syphilis epi and cause

Answer 126

• Caused by T pallidum endemicum
• Arid, warm climates of North Africa and Arabian Peninsula
• Children <15 years

Question 127

Endemic syphilis clinical

Answer 127

• primary lesion rarely noticed - inconspicuous small papule or ulcer in the oropharynx or nipple in breastfeeding women
• Secondary:
  
  • venereal syphilis similar, patches on mucous membranes, split papules, angular stomatitis, non-pruritic papular skin eruptions, condymoma lata.
  • Osteoporosis and leg pain at night
• Tertiary: 6 months - several years: gumma –> skin, MM, mm, cartilage, bone

Question 128

Endemic syphilis histo

Answer 128

Early: perivascular dermal infiltrate of plasma cells and lymphocytes

Question 129

Endemic syphilis ddx

Answer 129

• Oral: venereal syphilis, aphtthosis, perleche, vitamin deficiency, HSV
• Nasopharyngeal mutilations: tertiary venereal syphilis, leprosy, rhinoscleroma, mucocutaneous leishmaniasis, paracoccidiodomycosis, TB

Question 130

Sporotrichosis epidemiology

Answer 130

• Endemic to Mexico, Central and South America
• Those who get it typically work outdoors or are gardeners
• Sphagnum moss is often implicated
• more common in adults

Question 131

Sporotrichosis pathogenesis

Answer 131

• cutaneous inoculation - by vegetation such as thorns and wood
• also can be from cats in Brazil
• multiple inoculations can happen simultaneously
• clinical depends on host immune response
• if have had before, usually just have granulomatous plaque or ulcer without lymphatic spread
• immunosuppressed: can have extensive cutaneous or systemic involvement

Question 132

Sporotrichosis clinical

Answer 132

• Single papule at site of injury –> erodes and ulcerates with purulent drainage
• Not painful
• Additional lesions appear weeks later along a lymphatic path (sporotrichoid)
• Lymph vessels may become fibrosed
• Fixed cutaneous sporotrichosis can have a granulomatous apperarance, often with ulceration whereas disseminated are more subcutaneous nodules

Question 133

Sporotrichosis histology

Answer 133

• Suppurative and granulomatous inflammation
• Causative organism is rarely evident
• Staining fluorescent labeled antibodies may aid in recognition of cigar shaped yeast
• Asteroid bodies often seen
• When numerous: can see with PAS or silver stains
• Micro: dimorphic fungi, grows rapidly at 25 degrees

Question 134

Sporotrichosis ddx

Answer 134

• Atypical mycobacterium: M marinarum

- Non and infectious granulomatous

Question 135

Sporotrichosis rx

Answer 135

• Oral potassium iodide - affects host’s immune reaction to the organism (careful of iododerma, GI upset and thyroid suppression)
• Itraconazole - 3-6 monthly

Question 136

Leptospirosis

Answer 136

• Caused by spirochete in the genus Leptospira
• Transmitted: non-intact skin/mm with body fluids (not saliva) from infected mammals. Often from drinking or swimming in contaminated water
• See it ins vets, farmers, slaughterhouse, sewer workers, recreational water sport
• 90% anicteric, 10% severe icteric
• Stages:
  1. Incubation - 7-12 days
  2. Septicaemic - fevers, chills, myalgias
  3. Immune stage (positive test) - meningitis, uveitis, renal, hepatic, pulmonary. Cutaneous: erythematous macules, papules, patches, plaques in a widespread distribution or just on the shins, as well as petechiae and purpura secondary to vascular involvement
• Rx: self-limited, but antibiotics reduce duration and shedding: PO doxy, amox, azithromycin. If severe - IV penicillin, third gen cephalosporin

Question 137

Actinomycoses epi and path

Answer 137

• M>F 3:1
• Actinomyces israelii - anaerobic or microaerophilic gram positive, non-acid fast actinomycete is the most common organism
• A israelii is part of the normal flora of the oral cavity and the GIT and female genital tract
• Trauma (particularly dental) predisposes
• Not overly pathogenic, but its virulence is enhanced by co-infection

Question 138

Actinomycoses clinical

Answer 138

• Cervicofacial: history of poor dental hygiene or an injury here. Initial bluish swelling in the mandibular area progresses to brawny, erythematous nodules which gradually increase in size and form fistulous abscesses. these drain yellow ‘sulfur granules’ that represent clumps of bacteria. have multiple sinus tracts, fever, pain, leukocytosis
• Pulmonary: (15-20% of patients) - aspirate into the lungs, develop pleurocutaneous fistulas
• Gastrointestinal: granulomatous lesions involving the bowel, can eventually extend to the abdominal wall
• Pelvic - in women, from IUD

Question 139

Actinomycoses histo

Answer 139

• Intense neutrophilic infiltrate followed by development of granulomatous inflammation with giant cells
• Periphery of abscess: histiocytes, plasma cells, epithelioid cells
• Characteristic sulfur granules: basophilic centre and acidophilic periphery

Question 140

Actinomycoses microscopic findings

Answer 140

Microscopic: gram positive branching filaments that fragment into diphteroid forms and coccobacilli, acid fast negative

Question 141

Actinomycoses rx

Answer 141

• Penicillin G or ampicillin
• Deep-seated chronic: IV for 2-6 weeks then 3-12 months of oral penicillin
• Acute - may need 2-3 weeks of oral penicillin plus incision and drainage
• If can’t have penicillin consider doxy, erythromycin, clindamycin

Question 142

Nocardiosis epi and path

Answer 142

• worldwide distribution and affects all age groups
• Men > F 3:1
• kids more prone to developing lymphocutaneous disease
• Nocardia ubiquitous in soil. Is a filamentous, Gram-positive, acid-fast organism
• Localized trauma, occupational exposures and immunodeficiency are risk factors

Question 143

Nocardiosis clinical

Answer 143

1. Mycetoma
   
   1. Traumatic inocculation –> painless nodule that enlargens, suppurates and drains via sinus tracts
   2. Purulent discharge has sulfure granules
   3. Foot - most common site, may involve muscle and bone
2. Lymphocutaneous
   
   1. Occurs days-weeks after trauma
   2. Crusted pustule or abscess resistant to antibiotics
   3. Ascending lymphatic streaks in a sporotrichoid pattern of papulonodules, with tender lymph nodes
3. Superficial cutaneous
   
   1. Traumatic implantation into the skin
   2. Diagnosis is based on high index of suspicion
4. Pulmonary-systemic - 10% develop cutaneous lesions as secondary skin lesions
   
   1. Subcutaneous abscesses of the chest wall
   2. Pustules, nodules, cutaneous fistulae
   3. Fatal if untreated
   4. Most common: nocardia asteroides

Question 144

Nocardiosis path

Answer 144

• Intense neutrophilic infiltrate with abscess formation
• Sulfur granules in Nocardia mycetoma
• Gram stain: branching filaments
• Nocardia also stains with methenamine silver and acid-fast stains

Question 145

Nocardiosis treatment

Answer 145

• Sulfonamides –> 6-12 weeks, if immunocompromised 3-12 months
• Second line: minocycline
• Resistant: linezolid
• If subcutaneous abscess - surgical treatment

Question 146

Bartonella info

Answer 146

small, pleomorphic facultative intracellular gram-negative bacilli

Question 147

Bartonellosis

Answer 147

• caused by bartonella bacilliformis, transmitted by sand flies
• occurs in Peru
• Clinical:
  
  • 1. Oroya fever - acute febrile illness with haemolytic anaemia
  • 2. Peruvian wart - those who recover from Oroya fever develop cutaneous nodules, and peruvian warts - bright red papules and nodules, can be sessile or pedunculated. Haemorrhage, ulceration and secondary bacterial infection can occur. Heals without scarring
• Histo: pyogenic granuloma or Kaposi, Rocha-Lima inclusions (intracytoplasmic Bartonella organisms)
• Ddx: pyogenic granulomas, bacillary angiomatosis, warts, molluscum, yaws
• Rx: chloramphenicol + beta-lactam, for verruga peruana - azithromycin

Question 148

Cat scratch disease

Answer 148

• Younger people
• Caused by Bartonella henselae, transmission is by a flea vector
• Clinical: persistent lymphadenopathy, suppuration, +/- systemic features, plus other things, can get unilateral conjunctivities and ipsilateral preauricular lymphadenopathy in 5% of CSD
• Histo: lymph nodes have central necrosis and palisading histiocytes and epithelioid cells
• Dx: regional adenopathy + cat scratch –> diagnosis usually
• Rx: clarithromycin

Question 149

Bacillary angiomatosis

Answer 149

• Bartonella henselae or quintana –> can be through cats or lice.
• Commonly seen in HIV affected patients with low CD4 counts –> so mainly see in AIDS patients
• May reflect aberrant VEGF signalling –> develop vascular like tumours
• Clinical: superficial angiomatous papules and nodules, violaceous lichenoid plaques, deep subcutaneous nodules, they look like pyogenic granulomas. Rarely can involve the underlying bone. Can have multiple, feel quite solid.
• Immunocompetent: usually single lesion at site of innoculation, but immunosuppressed have multiple
• Extra-cutaneous: may occur with GIT involvement
• Histo: lobular proliferations of capillaries and venules, plump endothelial cells, marked neutrophilic infiltrate, leukocytoclasis. Bacteria seen on Warthin-Starry stain
• Dx: PCR rapid and sensitivte, and you can grow it but takes 20-40 days
• Ddx: pyogenic granuloma, Kaposi sarcoma, cherry angioma, angiokeratomas, verruga peruana, disseminated myocbacterial infection
• Histo ddx: verruga peruana, Kaposi, pyogenic granuloma, angiosarcoma
• Rx: begin to improve within 1 week of antibiotics, and resolve completely within 4 weeks –> doxy and arythromycin. Treat for at least 3 months, as therapeutic failures can occur with shorter courses, surgical excision of solitary cutaneous

Question 150

Scabies epi

Answer 150

• Risk factors: overcrowding, delayed treatment, lack of awareness
• Transmitted: direct close contact or indirectly via fomites
• Crusted scabies: found in immunosuppressed - elderly, HIV, transplant recipients, and those with sensory function issues (paraplegia)

Question 151

Scabies pathogenesis

Answer 151

• Cause: Sarcoptes scabiei hominis
• Entire life cycle of the mite is 30 days - each day a female mite lays 3 eggs, which take ~ 10 days to mature
• Number of mites on a host varies greatly
• Crusted scabies - ++ more, and more in environment as well
• Scabies lives 3 days off a human, but crusted scabies can be up to 7 days
• Incubation period - days to months
• First-time: immune system takes 2-6 weeks to become sensitised and result in pruritic and cutaneous lesions
• Some people can carry them and be asymptomatic

Question 152

Scabies clinical

Answer 152

• Cutaneous lesions are symmetrical - involving the interdigital web spaces, flexures, waist, groin, feet, buttocks, penis, areolae, nipples
• Excoriations, vesicles, indurated nodules, eczematous dermatitis, secondary bacterial infection
• Pathognomonic: burrow - wavy, thread-like grayish-white and 1-10 mm in length
• Many patients dont have obvious burrows
• Acral vesiculopustules: clue in infants
• Crusted - marked hyperkeratosis that favours acral sites
• can be secondary bacterial infection
• Peripheral eosinophilia

Question 153

Scabies histo

Answer 153

• Infiltrate with prominent eosinophils, and lymphocytes, histiocytes
• Transected scabies mite
• Pink ‘pigtail’ like structures attached to the stratum corneum - represents fragments of adult mite exoskeleton

Question 154

Scabies ddx

Answer 154

• Eczema, contact, nummular dermatitis
• Arthropod bites
• Pyoderma
• DH
• BP
• LCH
• Acropustulosis of infancy

Question 155

Scabies rx

Answer 155

• Two topical treatments 1 week apart
  
  • apply overnight to the entire body surface from head to toe in infants and the elderly, or skip face in other groups
  • clothing, linens, towels from the previous week be washed in hot water and dried on high heat or stored in a bag for 10 days
  • pets cannot harbour human mites
• Treatment options:
  
  • Permethrin (Lyclear) - days 1 and days 8
    
    • MOA: inhibits sodium transport in athropod neurons –> paralysis
    • –> can get ACD to formaldehyde
    • can use on infants >2 months
    • Pregnancy B
  • Lindane lotion - days 1 and 8
    
    • A/E CNS toxicity, especially <50 kg
    • Resistance common
    • Not recommended for infants or kids or breastfeeders
    • Pregnancy C
  • Sulfur ointment - topically overnight for 3 successive days
    
    • Considered safe
  • Ivermectin - 200-400 microg/kg on day 1 and day 8 or 14
    
    • MOA: blocks GABA and glutamate - resulting in paralysis of peripheral motor function in insects and acarines
    • A/E potential CNS toxicity in young, although overall pretty safe
    • Does not penetrate for subungual scabies
    • Safety not established for kids and prengancy
    • Pregnancy C
• Can develop post-scabetic pruritus or dermatitis, and can persist for 2-4 weeks after treatment completion
• many experience relief within 3 days
• Second application is for reinfestation from fomites and kill off eggs

Question 156

Brucellosis

Answer 156

• Cause: Brucella - genus of gram negative coccobacilli
• Most common zoonosis worldwide - endemic to parts of Asia
• Transmission: consumption of contaminated unpasteurized milk products, direct contact with infected animal parts or inhalation of aerosolized particles
• Clinical: very variable
  
  • Cutaneous: disseminated violaceous papulonodules, EN, vasculitis - <10% of patients
  • Systemic: arthralgias, fever, malaise, headache, CNS, ocular, pulmonary, cardiovascular, GIT, genitourinary
  • Chronic: afebrile, but experience arthralgias, headaches, myalgias, diaphoresis, cyclic depression, malodorous perspiration (highly characteristic)
• Rx: multi-drug regime: doxycycline 6 weeks plus streptomycin, or rifampicin

Question 157

Glanders

Answer 157

• Cause: Burkholderia mallei - non-motile, strictly aerobic, non-pigment producing gram negative bacillus
• Endemic in Africa and Asia and South America
• Transmitted through direct contact with infected animals
• Clinical forms:
  
  • 1. Septicaemic
  • 2. Localized –> nodule, pustule or vesicle surrounded by haemorrhagic oedema at the inoculation site –> then ulcerates with gray-brown base, may also involve nose and cause ulceration of nasal septum or palate
  • 3. Pulmonary
  • 4. Chronic –> can get painful subcutaneous and intramuscular abscesses - ‘farcy buds’ –> appear along draining lymphatics
• So consider it when there are localized cutaneous abscesses and secondary lesions in a sporotrichoid fashion
• Dx: PCR
• Rx: 60-150 days of augmentin, doxy, tmp-smx

Question 158

Meliodosis

Answer 158

• Cause: Burkholderia pseudomallei - mobile, aerobic, intra-cellular spore-forming bacillus in soil and water
• Endemic: northern Australia, SE asia
• Transmission: abraded or lacerated skin in contact with contaminated soil or water, or through ingestion, inhalation, sexual intercourse
• Risk factors: DM, CKD
• Clinical types:
  
  • Acute - sepsis has mortality rate of 50-90% without ICU admission
  • Subacute - predominantly pulmonary disease
  • Chronic - abscesses, granulomas
  • Cutaneous in acute or chronic: cellulitis, subcutaneous abscesses, granulomatous lesions, echthyma gangrenosum, purpura, pustules, urticaria
• Dx: bacterial culture, sensitivity is low (60%), can do PCR
• Rx: initial IV ceftazidime or a carbapenem for 10-14 days, followed by eradication with RMP-SMX or augmentin for >3 months

Question 159

Malacoplakia

Answer 159

• Is a granulomatous response with impaired macrophages that can’t phagocytose and kill bacteria properly
• Occurs in immunocompromised people
• Due to E coli most commonly, but can be from multiple
• Clinical: genitourinary tract most affected, cutaneous - peri-anal ulceration, abscesses, draining sinuses, yellow-pink soft papules, indurated nodules
• Histology:
  
  • Michaelis-Gutmann bodies - intracytoplasmic laminated concretions –> indicated accumulation of calcified, iron containing phagolysosomes. These stain with PAS, von Kossa, Perls’ and Giemsa
  • Von Hansemann cells - large macrophages that contain Michaelis-Gutmann bodies - positive for CD68, lysozyme and alpha-1 antitrypsin
  • Ddx: infectious granulomas, LCH, granular cell tumour, fibrous histiocytoma
• Rx: difficult, local –> excision, prolonged abx, vitamin C and bethanechol chloride to improve macrophage function

Question 160

Tularemia

Answer 160

• Caused by Francisella tularensis - Gram negative, non-motile coccobacillus
• Reservoir: rabbits, hares, ticks
• Portal of entry: skin abrasion, inhaled, ingested (last 2 pretty rare)
• Six clinical forms:
  
  • 1. Ulceroglandular –> most common, lymphadenopathy and erythematous, indurated, punched-out ulcer
  • 2. Glandular
  • 3. Oropharyngeal/gastrointestinal
  • 4. Typhoiddal/septicaemic
  • 5. Oculoglandular
  • 6. Pneumonic
  • Rare cutaneous: buboes, morbilliform or vesicular eruption, EN, EM
• There is concern this will be used as a biologic weapon
• Diagnosis: direct fluorescent antibody, PCR, immunohistochemical staining
• Ddx: other ulceroglandular things - place, TB, rat-bite fever, glanders, anthrax, soft tissue infection
• Rx: streptomycin for 10 days
• Can have Jarisch-Herxheimer-like reaction following initiation of therapy
• No vaccine now

Question 161

H influenzae cellulitis

Answer 161

• Gram negative coccobacillus
• Causes facial cellulitis with a violaceous hue in infants and young children following an URTI
• Favours the buccal and periorbital areas, and is associated with high fevers, leukocytosis and positive blood cultures
• Cx: meningitis
• Rx: third gen cephalosporin

Question 162

Rhinoscleroma

Answer 162

• Slowly progressive, chronic granulomatous infection in nose and URT
• Pathogenesis:
  
  • Caused by Klebsiella rhinoscleromatis - this is a subspecies of Klebsiella pneumoniae
  • Endemic to tropical areas - i.e. central america
  • Transmission through inhaled contaminated droplets
  • The host usually has immunodeficiency which results in ineffective phagocytosis
• Clinical stages:
  
  • 1. Rhinitis
  • 2. Granulomatous nodules, epistaxis, dysphonia, etc
  • 3. Sclerotic: nodules replaced by fibrous tissues with resultant extensive scarring and stenosis
• Diagnosis:
  
  • Mikulicz cells: large, vacuolated non-lipidized histiocytes with intracellular bacteria
  • Russell bodies: plasma cells with aggregates of condensed immunoglobulins
  • Stain: PAS, Giemsa, silver, gram stains
  • Culture only positive for 50% of cases
  • CT: ‘crypt-like’ irregularities
• Ddx: leishmaniasis, paracoccidiodomycosis, rhinosporidiosis, leprosy, yaws, tertiary syphilis, nasla TB, sarcoidosis, GPA, Rosai Dorfman (histologically)
• Rx: abx for 6 months or until nasal biopsy negative –> tetracyclines, sclerotic lesions respond to ciprofloxacin

Question 163

Salmonellosis

Answer 163

• Spectrum of infections caused by Salmonella - gram negative aerobic bacilli
• Typhoid is due to S typhi
  
  • direct contact spread between humans
  • Systemic: fever, headache, malaise, cough, etc
  • Rose spots - pink, blanching, slightly elevated papules on anterior trunk, groups of 5-15 lesions. Occurs in 30% of patients with typhoid fever. Rose spots occur in crops during second to foruth weeks of illness –> Salmonella can be cultured from these
  • Other: EM, Sweets, haemorrhagic bullae, pustular dermatitis, generalized erythematous eruption - erythema typhosum
  • Dx: culture from BM most sensitive but obviously won’t do, cultures are less sensitive and PCR-based detection is limited by low microbial DNA in samples
  • Rx: quinolones, ceftriaxone, azithromyci

Question 164

Rat bite fever

Answer 164

• Cause: Streptobacilus moniliformis and in Asia Spirillum minus - Sodoku
• Transmission: rat bite, close contact, contaminated food, etc
• Seen in urban areas with poor sanitation, and 50% children
• Clinical: fever, rash and arthralgia
  
  • Bite: erythema, oedema, abscess formation, ulceration, secondary infection
  • Paroxysms with fever interspersed with afebrile periods, as well as headaches, nausea, vomiting etc
  • Hallmark: migratory polyarthritis in 50%, mimics RA
  • After 2-4 days: acrally distributed eruption involving the palms and soles which is polymorphic
• Dx: bloods culture, synovial fluid culture –> Spirillum minus doesn’t grow in regular culture
• Ddx:
  
  • Infectious: viral, Rocky mountain spotted fever, meningococcaemia, rheumatic fever, secondary syphilis
  • Non-infectious: Still disease, SLE, serum sickness like drug reactions, Sweets, Schnitzler
• Rx: penicillin. 10-15% cases are fatal

Question 165

The plague

Answer 165

• Caused by Yersinia pestis - gram negative, rounded bipolar bacillus transmitted by fleas and rodents
• Highest incidence: Southeast Asia, and northern New mexico and California
• Clinical forms:
  
  • 1. Bubonic - Inoculation –> pustule or ulcer, regional lymphademopathy (bubo), suppuration and discharge from lymph nodes
  • 2. Septicaemic –> vesicles, carbuncles, petechiae, purpura
  • 3. Pneumonic
• Ddx: tuluraemia, rat bite fever, sporotrichosis, tuberculosis, strep echthyma, syphilis, LGV
• Untreated - 40-60% fatality for bubonic, the others are
• Rx: streptomycin and aminoglycosides, second line doxy and quinolones
• Post-exposure prophylaxis with doxy or cipro
• Do have a vaccine but poor safety profiles

Question 166

Vibrio vulnificus

Answer 166

• Vibrio constitutes a group of gram-negative anaerobic bacteria
• Risk factors: men >40 years, liver disease, DM, immunosuppression, history of exposure to warm seawater or raw/undercooked seafood, impaired skin integrity
• Clinical: fevers, chills, nausea, vomiting, diarrhoea
• Cutaneous - 75%, erytehmatous and purpuric macules to vesicles and haemorrhagic bullae –> then necrotic ulcers similar to purpura fulminans
• Can progress to necrotizing fasciitis or myositis
• Rx: doxy PO or IB + third gen cephalosporin

Question 167

Mycobacteria background

Answer 167

• Organisms are thin, slightly curved to straight, non-motile and non-spore forming with a waxy coating which makes then resistant to stains
• Acid-fast –> not readily decolorized by acid after staining
• Mycobacteria are classified into slow growers, rapid growers

Question 168

Leprosy epidemiology

Answer 168

• Number of new cases worldwide ~210 000 in 2015. Highest incidence in Americas in Brazil
• WHO goal is <1 case per 10 000
• F=M
• Lepromatous twice more likely in men than in women (?worse immune system)
• Bimodal peaks: 10-15 years and 30-60 years
• Transmission: close or intimate contact, nasal and oral droplets, much less often from eroded skin
• Incubation period: months to >30 years, but usually 4-10 years
• Even after 1-7 days, the bacillus is still viable in dried secretions
• Other animals: can be found in nine-banded armadillos, red squirrels and mice

Question 169

Leprosy pathogenesis

Answer 169

• M Leprae
  
  • Very small, slightly curved, obligate intracellular, acid-fast
  • Prediliction for macrophages and Schwann cells
  • Requires ~ 35 degrees to grow, prefers cooler regions of the body and peripheral nerves close to the skin
• Genetics
  
  • HLA-DR2 and HLA-DR3 more likely to develop tuberculoid form
  • HLA-DLQ1 more likely to develop lepromatous
  • Susceptibility gene that has been found that shares with a Parkinson disease gene PARK2
  • Innate immune response defects –> NOD2 pathway genetic mutation
• Immunity
  
  • Depending on the level of specific cell-mediated immunity, the disease can progress, limit or resolve spontaneously
  • Humoral immunity increased in forms that are associated with minimal cell-mediated immunity
  • When macrophages encounter the M leprae –> secrete IL-1, TNF and IL-12 which stimulates more macrophages
  • Tuberculoid is TH1 CD4 T cell response:
    
    • Produces IL-2, interferon gamma and lymphotoxin alpha –> granulomatous
    • CD4 cells also secrete high levels of anti-microbial protein granulysin
    • Have a stronger expression of TLR2 and TLR1 which can induce differentiation of macrophages and dendritic cells
  • Lepromatous is TH2 CD8 response:
    
    • IL-4, IL-5 and IL-10 and IL-13 –> suppress macrophage activity
    • Have higher leukocyte immunoglobulin like receptor - this suppresses innate host defense
  • M leprae contains lipid complexes - PGL-1 may suppress T cell responses and IFN-gamma production

Question 170

Leprosy clinical subtypes

Answer 170

Ridley and Jopling are the most accepted

• Lepromatous –> immunodepressed
• Borderline lepromatous
• Borderline borderline
• Borderline tuberculoid
• Tuberculoid - immunocompetent with granulomatous response
• Indeterminate

WHO 1997 has subtypes but not that helpful

• Paucibacillary - single lesion
• Pauciballary leprosy - 2-5 skin lesions
• Multibacillary - more than 5 skin lesions

Question 171

Leprosy neuro manifestations

Answer 171

• Peripheral nerves that become enlarged and palpable
• Nerves commonly affected: facial nerve branches, median nerve, greater auricular nerve, ulnar and radial, cutaneous branch of the radial nerve, common peroneal, posterior tibial
• Sensation: hypaesthesia and anaesthesia
• Neuropathic changes: muscle atrophy, flexion contracture of the fourth and fifth fingers, vasomotor alteration, secretory disturbances

Question 172

Head to toe leprosy sequelae

Answer 172

• Face: leonine facies, madarosis, saddle nose, elongated soft ear lobes
• Ocular: lagopthalmos, corneal anaesthesias, keratitis, episcleritis, blindness
• Chest: gynaecomastia
• Hands:
  
  • Papal hand - flexion contractures of 4th and 5th fingers
  • Claw hand
  • Shortening of digits (bone resorption)
• Testes: orchitis leading to sterility
• Legs:
  
  • Acquired ichthyosis
  • Neurotrophic ulcers
  • Foot drop
  • Hammer toes

Question 173

Lepromatous leprosy

Answer 173

• Florid diffuse symmetric: macules, papules, nodules
• Common sites: face, buttocks, lower extremities
• More likely to have facial invovlement, ichthyosis and ocular involvement
• Difficult to differentiate from normal skin
• ?Sensation not affected, occasionally anaesthesia in a stocking or glove distribution
• Lots of bacilli in the skin, easy to diagnose
• Histoid leprosy: is a subtype, dermatofibroma like papules and nodules

Question 174

Borderline leprosy

Answer 174

• Tends to be symmetric, less well-defined borders
• Macules, papules, plaques, infiltration –> often in plaques the hair is usually absent
• May have unilateral earlobe swelling
• Sensation diminished
• ++ bacilli

Question 175

Borderline borderline leprosy

Answer 175

• Plaques and dome-shaped, punched out lesions
• Asymmetrical, can have many lesions
• Well defined borders
• Sensation diminished
• ++ Bacilli

Question 176

Borderline tuberculoid leprosy

Answer 176

• Infiltrated plaques, usually single with satellite lesions to around 5
• Asymmetric
• Well defined, sharp borders
• Sensation absent
• Few bacilli

Question 177

Tuberculoid leprosy

Answer 177

• granulomatous, infiltrated plaques, often hypopigmented
• Single or few lesions, sometimes just neural involvement
• Borders are slightly elevated –> preferred site for biopsy
• Unilateral neuropathic changes may be seen
• Localised, asymmetric
• Sensation absent
• No bacilli

Question 178

Indeterminate leprosy

Answer 178

• Macules, often hypopigmented
• Impaired sensation
• One or a few lesions, variable distribution

Question 179

Cause of leprosy reactions

Answer 179

causes of reactions: anti-microbial drugs, pregnancy, infections, mental distress

Question 180

Type 1 leprosy reaction

Answer 180

Type 1 - reversal

• Patients with any form of leprosy except early indeterminate, predeliction for those in borderline categories
• Increase in cell mediated immunity –> ‘upgrading’ reaction
• Immune mechanism: enhancement of cell-mediated immunity with a Th1 cytokine pattern –> gets more granulomatous, tuberculoid
• Delayed-type hypersensitivity reaction
• Clinical:
  
  • increase in inflammation in established skin lesions
  • emergence of ‘new’ skin lesions
  • acute nerve pain or tenderness and loss of function
  • recent or progressive neurologic impairment in the absence of painful nerves
• Rx: prednisone

Question 181

Type 2 leprosy reaction

Answer 181

Type 2 - vasculitis

• most often occurs in lepromatous or borderline lepromatous leprosy –> especially patients with a high bacterial index who are undergoing treatment
• Th2 cytokine pattern - excessive humoral immunity, formation of immune complexes, increased cell-mediated immunity
• Clinical:
  
  • Cutaneous and systemic small vessel vasculitis
  • Nodular skin lesions - erythema nodosum leprosum
  • Fevers, myalgias, malaise
  • Severe joint swelling and pain
  • Iridocyclitis, lymphadenitis, hepatosplenomegaly
  • Orchitis
  • GN
  • Rare subtype: Lucio phenomenon - reactional state characterized by thrombotic phenomena in addition to necrotizing cutaneous small vessel vasculitis. Usually in Central and South America.
• Rx: Thalidomide

Question 182

Leprosy histology and stains

Answer 182

1. Lepromatous
   - Grenz Zone
   - Infiltrate in the dermis and subcutis –> contains Virchow cells - these are macrophages with numerous bacilli as well as lipid droplets in their cytoplasm, have a foamy appearance. Also contains plasma cells and lymphocytes.
   - Variant: histoid - well circumscribed proliferation of spindle cells containing numerous bacilli, which typically line up along the long axis of the cell
   - Stains: Gram, Ziehl-Neelson, Fite (most commonly used - causes bright red colour), and Methenamine silver can be helpful looking for fragmented acid-fast bacilli (for when organisms fragment during treatment)
   
   • If can’t see bacteria - recommend looking at at least 6 sections before calling it
     - Cutaneous nerve: lamination of the perineurium producing an onion skin like appearance
2. Tuberculoid
   - Dermal, granulomatous infiltrate, may have a linear pattern following the course of the nerve
   - Epithelioid cells and Langhans giant cells surrounded by lymphocytes
   - Cutaneous nerve: oedematous, minimal orgnaisms
   - Inflammation and fragmentation of nerve fibres differentiates it from other granulomatous reactions
3. Borderline
   - Has both lepromatous and tuberculoid
4. Indeterminate
   - Difficult to dx histologically
   - patchy infiltrate of lymphocytes or histiocytes around blood vessels or appendages
   - no granulomas or Virchow cells

Question 183

Leprosy investigations

Answer 183

• Bacilloscopy
  
  • From earlobes, forehead, chin, extensor forearms, dorsal fingers, buttocks, trunk
  • Fold of skin squeezed and small incision with scalpel –> smear onto a slide and dry, then stain with Fite or Ziehl-Neelson and search is made for red rods against a blue background at 100X with oil immersion
  • Lepromatous leprosy will always have organisms, BL 75%, TL 5%
• Other tests:
  
  • PCR
  • Serologic assay with anti-PLG antibodyes and IgM antibodies
  • VDRL for syphilis false positive in leprosy
• Other skin tests:
  
  • Histamine: looks for wheal and flare
  • Pilocarpine: iodine test placed on area, turns blue if normal sweating
  • Lepromin: intra-dermal injection of heat killed M leprae –> positive when a nodule forms at site 3-4 weeks later, shows has mounted a response

Question 184

Leprosy ddx

Answer 184

• Hypopigmented: MF, sarcoidosis, PIH
• Annualr: MF, sarcoid, psoriasis, intersitital granulomatous dermatitis, GA, tinea corporis
• Plaques and nodules: lymphoma, sarcoiosis, other infections
• Neuro: peripheral neuropathy from other disorder
• Acral deformities: sclerosis, tabes dorsalis, dupuytren
• Type 1: ACLR, cellulitis, drug reaction
• Type 2: Sweets, vasculitis, panniculitides, infections

Question 185

Leprosy Rx

Answer 185

• Paucibacillar but can’t see bacilli: rifampicin 600 mg monthly + dapsone 100 mg daily for 6 months, observe for 2 years
• Paucibacillary and a single lesion: ROM - rifampicin 600 mg monthly, ofloxacin and minocycline
• PB and 2-5 lesions: rifampicin 600 mg monthly, dapsone 100 mg daily for 6-9 months
• If at least one bacillus: rifampicin 600 mg monthly, clofazamine 300 mg monthly and 50 mg daily, and dapsone 100 mg daily for 1-2 years, and observe for 5 years
• Multibacillary: rifampicin 600 mg monthly, clofazamine 300 mg monthly and 50 mg daily, dapsone 100 mg daily for 12-18 months
• Rifamp always 600 mg monthly, clofaz 300 mg monthly and 50 mg daily, dapsone 100 mg daily
• After first dose, no longer infectious. Once regime complete, virtually no relapses
• Type 1: oral pred 20-60 mg daily
• Type 2: thalidomide, lenalidomide, pomalidomide, possibly cyclosporin
• Lucio: prednisone

Question 186

Sporotrichoid spread ddx

Answer 186

CATNSPLAT
Cat scratch bartonella henselae/quintane
Cryptococcosis/blastomycosis
Atypical mycobacteria (marinarum)
TB
Nocardia
Sporotrichosis
Staph
Phaehyphomycosis
Leishmaniasis
Anthrax
Tuluraemia

Question 187

TB epi

Answer 187

• Only 5-10% of infections lead to clinical disease
• Worldwide distribution, more prevalent in regions with a cold and humid climate, can occur in the tropics
• Higher in low-income and impoverished populations
• Higher in immune defects: HIV, immunosuppressed (TNF alpha inhibitors), and innate defects in IL-12/IFN gamma axis

Question 188

TB pathogenesis

Answer 188

• Causative agent
  
  • M tuberculosis predominant agent, occasionally M bovis and bCG (attenuated strain of M bovis)
  • M tuberculosis - slender, non-motile aerobic, non-spore forming filamentous rod
  • Acid and alcohol fast, has a waxy coating with a high lipid content –> this makes it resistant to degradation after phagocytosis
• Transmission
  
  • Inhalation of aerosolozed droplets of saliva, more rare ingestion or inoculation through mucocutaneous break
• Immune dysfunction
  
  • Untreated infected individuals who do not have immune impairment or medical problems have a 5-10% lifetime risk of progression to active TB
  • Immunosuppressed increases risk
  • T cells and mycobacterial antigens promote interferons and cytokines –> IL-2 on T cells and MHC class 2 on APC
  • Initial sensitisation: memory T cells remain for decades in lymphoid organs
  • IFN-gamma induces nitric oxide: modulates macrophage responses and represses neutrophil recruitment cascade
• Granuloma formation
  
  • Evidence that granulomas actually contribute to early bacterial growth and facilitate the spread of infection
  • The mycobacteria itself secretes ESAT-6 protein, which stimulates neighbouring epithelial cells to produce MMP9, which enhances recruitment of macrophages that contribute to bacterial proliferation and spread, plus helps grow a granuloma
  • Also secretes MMP1 and MMP3 which drives tissue destruction
  • Eventually, the development of adaptive immunity results in the curtailment but not eradication of bacterial growth by CD4 and CD8 T cells
  • Mature granuloma represents an equilibrium between mycobacterial growth and host immune response
• Genetic
  
  • IPR1 gene mutation
• Ultimately depends on: mycobacterial antigens, degree of cell mediated immunity, route of infection, pathogenicity fo infective strain

Question 189

Tuberculous chancre

Answer 189

• Initially bacilli –> granulomatous reaction –> fades
• From inoculation in someone with no immunity to TB
• Rare, except in Asia, accounts for 1-2% of cutaneous TB
• 2-4 weeks post innoculation –> painless, firm, red-brown papulonodules that slowly enlarge and erode into a sharply demarcated ulcer
• Drains to regional lymph nodes –> lymphadenopathy
• Occasionally evolve into verrucous plaque, scrofuloderma or lupus vulgaris
• Commonly heal spontaneously within 3-12 months, leaves atrophic scar and calcified nodules
• Dx: histo, culture, PCR, IGRA –> tuberculin test later positive
• Histo: necrosis and bacilli with neutrophilic inflammation, later develops granulomatous inflammation with central caseation, epithelioid, Langhans
• Ddx: sporotrichosis, fungal infections, mycobacteria: marinum, nocardiosis, tuluraemia, syphilis, cat scratch disease

Question 190

Tuberculous verrucosa cutis

Answer 190

• Exogenous inoculation in a previously infected person
• Immediate granulomatous response
• Accounts for 40% of TB
• Small, asymptomatic indurated wart-like papules that enlargen, often in a serpiginous manner, to form. a reddish-brown verrucous plaque
• Centre may become fluctuant with pus and keratinaceous debris expressed by slight pressure
• Heals spontaneously after several years
• Dx: culture, PCR, Quant Gold, skin test positive
• Histo: pseudoepitheliomatous hyperplasia, microabscesses in the upper dermis, spare granulomatous foci, occasional bacilli
• Ddx: warts, verrucal fungal infections, hypertrophic lichen planus

Question 191

Scrofuloderma

Answer 191

• Contiguous involvement of the skin overlying a focus of TB, can also be from BCG vaccination
• Common in developing countries
• Firm, deep-seated subcutaneous nodule that has necrotic tissue and inflammatory material, ‘cold abscess’
• Becomes fluctuant and drains, with ulceration and sinus tract formation
• As it drains, infects the overlying dermis
• Borders are blue, margins are undermined, base has soft granulation tissue
• Can have multiple ulcers
• Healing: keloids and tethered scars
• Original focus of TB in lymph nodes, bones, joints, epididymis
• Dx: culture, PCR, Quant gold, positive TT
• Histo: tuberculous granulation tissue and caseation necrosis in the deeper dermis, bacilli can be isolated from pus
• Ddx: Fungal, non-TB mycobacteria, syphilitic gumma, actinomycosis, HS, severe acne conglobata

Question 192

Oroficial TB

Answer 192

• From autoinoculation of M TB
• Very rare
• Affected individuals typically have advanced systemic TB in the setting of impaired cell-mediated immunity
• mucosal or cutaneous lesions occur within or adjacent to a natural orifice that is draining an active T infection - pulmonary, intestinal, anogenital
• Most common site: mouth, particularly tongue
• Initially oedematous, red papule that ulcerates and develops undermined edges
• Ulcers are painful, recalcitrant to treatment and do not heal spontaneously
• Histo: nonspecific inflammatory infiltrate and necrosis, some tubercles with caseation in deep dermis, bacilli easily found
• Dx: histology and culture, PCR, presence of another focus of TB, IGRA
• Ddx: painful ulcerative diseases - HSV, recurrent aphthous stomatitis, pemphigus, histoplasmosis

Question 193

Lupus vulgaris

Answer 193

• Occurs in previously sensitised people who have a strongly positive delayed type hypersensitivity to tuberculin due to intact cell mediated immunity
• 10-15% of cases, women 2-3 X more
• Can be from direct extension, haematogenous or lymphatic spread, can develop from TB verrucosa cutis or scrofuloderma, or following BCG inoculation
• Red-brown plaque composed of papulonodules with apple-jelly on diascopy. As it expands, develops central scarring –> tissue destruction
• Types of presentations:
  
  • Plaque-type
  • Ulcerative or mutilating
  • Vegetating
  • Tumour like
  • Papulonodular
• Head and neck most commonly affected - nose, cheeks, ear lobes
• Tuberculin usually positive
• Histo: well-developed tubercles with scant caseation, nonspecific inflammatory infiltrate, no visible bacilli
• Dx: histo and culture, PCR, IGRA
• Ddx: sarcoid, DLE, fungal, leishmaniasis, tertiary syphilis, SCC

Question 194

Miliary TB

Answer 194

• Very rare, younger population
• Result of mycobacteraemia –> primary focus being the lungs
• pinhead sized bluish red papules capped by minute vesicles
• vesicles - tiny central umbilication followed by crusting
• when heal –> white scar with brownish rim
• Tuberculin test usually negative
• Histo: necrosis, nonspecific inflammatory infiltrate surrounded by macrophages, sometimes developing into small abscesses, abundant bacilli
• DxL smear, histology, culture, PCR< other focus
• Ddx: varicella, enteroviral exanthem, rickettsialpox, PLEVA

Question 195

Tuberculous gumma

Answer 195

• Seen in immunocompromised or kids from low SES
• Mycobacteraemia with cutaneous seeding
• Firm subcutaneous nodule that slowly softens or is an ill-defined fluctuant swelling
• Overlying skin breaks down to form an undermined ulcer, often with sinus tract formation
• extremities > trunk
• tuberculin usually negative
• Histo: massive necrosis and abscess formation, large number of bacilli
• Culture and histo, PCR, IGRA
• Ddx: panniculitis, fungal, syphilitic, gumma, HS

Question 196

Tuberculids

Answer 196

• immune reactions within the skin due to haematogenous dissemination of M TB or its antigens from a primary source, in an individual with strong antituberculous cell-mediated immunity
• begin as immune complex-mediated reaction, they evolve into a granulomatous inflammatory response
• pathogenesis is unclear –> have positive Tuberculin and have active TB, but can also have past TB, gets better with treatment, PCR positive –> so this pathogenesis is likely TB

Question 197

Papulonecrotic tuberculid

Answer 197

• Kids and young adults
• Dusky red papules or papulopustules that are widely distributed and symmetric, extensors and buttocks
• Asymptomatic usually
• Can have central necrosis, have spontaneous healing with scar formation
• Can have multiple cyclic eruptions
• Histo: LCV or granulomatous vasculitis, wedge shaped necrosis
• Ddx: PLEVA, LCV

Question 198

Lichen scrofulosum

Answer 198

• Very rare, seen in children with nodal or skeletal involvement, or post BCG
• Perifollicular pink or yellow-brown, tiny flat-topped papules with variable scale
• Clustered, predominantly on trunk
• Asymptomatic
• Persist for months, then leave without scarring
• Histo: superficial granulomas around hair follicles and sweat ducts, little or no caseation necrosis seen. No bacilli
• Ddx: lichen nitidus, LP, id reaction, Blau syndrome, sarcoidosis, secondary syphilis

Question 199

Erythema Induratum

Answer 199

• EI of Bazin for those related to M TB
• Immune complex deposition and delayed type hypersensitivity thought to be involved
• Females 80-90% of cases
• Begin after exposure to low temperature
• Subcutaneous nodules appear on the calves or both legs - may involute or break down, creating irregular deep ulcers with undermined bluish borders
• Heals leaving atrophic hyperpigmented scars
• Histology: lobular +/- septal, with neutrophilic vasculitis, thickening of S/C arteries and veins, perivascular cuffing, fat necrosis, granulomas, bacilli are absent and caseation is rare
• Other entities: EN, lupus miliaris disseminatus faciei, granulomatous rosacea, lichenoid tuberculid –> not tuberculid anymore

Question 200

BCG inoculation

Answer 200

• Attenuated M bovis
• Complications: localised or generalised tuberculids, lupus vulgaris, scrofuloderma, fever, inflammation, ulceration, oseitis, etc
• Rarely –> disseminated or even fatal infection in those with immunodeficiency affecting IL-12/interferon gamma access
• Injections of methanol extraction residue of BCG has been used as adjuvant immunotherapy in patients with melanoma and can also result in nodules and subcutaneous abscesses

Question 201

TB Dx

Answer 201

• Interferon gamma release assay
  
  • Quantiferon Gold or T-Spot
  • Determine whether exposure to recombinant peptides from M tuberculosis stimulates interferon gamma production by T cells
  • Greater specificity and similar sensitivity to tuberculin skin tests
  • Quantiferon higher specificity
  • T-spot higher sensitivity
  • Higher cost
  • Infections with mycobacteria can cause false positive
  • Better to do this in those who have had BCG inocculation
• Tuberculin skin test
  
  • low cost
  • requires 2 visits, results take 48 hours
  • vaccine can cause a false positive
  • infections with other mycobacteria can cause false positive
  • preferable in kids <5

Question 202

TB Rx

Answer 202

• First line agents
  
  • Rifampicin
  • Isoniazid
  • Pyrazinamide
  • Ethambutol
  • Rifapentine
  • Rifabutin
• CDC recommends teaching pulmonary TB:
  
  • Intensive: RIPE intensively for 8 weeks, then drop down to isoniazid and rifampicin for 18 weeks
  • Theres a few different regimens

Question 203

TB Drug resistance definition

Answer 203

• Multi-drug resistance definition:
  
  • Resistant to isoniazid and rifampicin –> ~3% of cases
• Extensively drug resistant:
  
  • to isoniazide, rifampicin, quinolones, at least one of 3 injectable second line drugs
  • Accounts for 10% of MDR-TB

Question 204

Cause of tinea nigra

Answer 204

Hortaea werneckii

Question 205

Cause of white piedra

Answer 205

Trichosporon
Scalp - ovoides
Pubic hair - inkin
Then cutaneum and loubieri

Question 206

Cause of black piedra

Answer 206

Piedraia hortae

Question 207

Cause of erysipeloid

Answer 207

Erysipelothrix rhusiopathiae

Question 208

White piedra - what does it look like

Answer 208

Non-dark hyphae with blastoconidia and arthroconidia

Grows as moist, cream coloured yeast like colonies, grows rapidly - looks like butter cream frosting

Question 209

Black piedra - what does it look like

Answer 209

Dark (dermatiaceous) hyphae with asci and ascospores

Slow-growing, dark green to dark brown black colonies on Sabourauds agar

Question 210

How does tinea versicolor fluoresce with woods lamp

Answer 210

Yellow

Question 211

What does tinea versicolor look like

Answer 211

Spaghetti and meatballs

Question 212

What does H werneckii look like

Answer 212

Pasty green-black colonies with yeast-like appearance

Question 213

Causes of tinea capitis

Answer 213

Microsporum canis
Trichophyton tonsurans
Trichophyton violaceous

Question 214

Casues of ectothris T capiitis

Answer 214

M canis - fluoresces yellow
M audouinii - fluoresces yellow
_ other microsporim
Rarely trichophyton rubrum

Question 215

Causes of endothrix T capitis

Answer 215

T tonsurans
T violaceoum
Won’t fluoresce

Question 216

Causes of favus T capitis

Answer 216

T schoenleinii - fluoresces blue-white

Question 217

What can help highlight fungal elements in KOH preparations

Answer 217

Chlorazol black E stain , and then calcofluor for fungal cell wall - apple-green fluorescence