W3P1 Flashcards
Where did HIV come from?
What are the two types?
Zoonotic disease
Made the leap to humans from African chimpanzees somewhere between 1911 and 1941
First documented case in humans: Kinshasa 1959
2 types of HIV:
HIV-1 and HIV-2
Which region has the greated HIV prevalence
Eastern and Souther Africa (20 /37 million)
Which provinces in Canada have the highest HIV rates?
Prairies (SK, MB) : because of high needle use
QC: because of immigrants from endemic areas
Demographic make-up of HIV infected population in Canada
Half - gay, bisexual and MSM
15%: drug users
of which 23% are female
ART stands for
Anti Retroviral Therapy
HIV stands for
Human Immunodeficiency Virus
HIV Life Cycle
The single stranded RNA virus is the INFECTIOUS form
In order for it to work it becomes double stranded DNA using reverse transcriptase
You need two receptors: the CD4 and the KEY: CXCR4 and chemokine receptors that live on our surfaces. If people are mutant and don’t have this receptor, they cannot get HIV/ they don’t have the key hole for the virus to enter the cell
Integrase: to combine viral DNA into host DNA
how does HIV enter cells
HIV (gp120)
Human T cell receptor
Human co-receptor (CCR5 or CXCR4 or both)
HIV
- What cells does it infect
CD4+ T lymphocytes*** Dendritic cells skin, lymph nodes, brain Macrophages CD8+ T lymphocytes Natural killer cells Natural killer T cells Viral reservoir
Where does HIV live?
LYMPHOID ORGANS
Peripheral lymph nodes
Gastrointestinal lymph nodes
- Neonatal transmission
Bone marrow
CENTRAL NERVOUS SYSTEM
HIV Tat protein disrupts the blood-brain barrier
- Microglial and dendritic cells
Reservoir for HIV replication
GENITOURINARY SYSTEM HIV crosses blood-testis barrier; infects semen Renal epithelium Macrophages and lymphocytes in cervix Reservoir for HIV replication
HIV mutation
Reverse transcriptase is extremely error-prone
High rate of genomic mutation
- Spontaneous mutations over time
- Many are silent/no-effect
- By chance alone some confer resistance to medications
Drug-driven mutations
- use of drugs increases mutant/resistance strains
Mutated vs Wild Type HIV when medications are given
By allowing viral replication to occur, mutants develop
A highly mutated HIV is a “less fit” virus, not as infectious
- Overtake wild type virus if medications are failing
- Less fit to replicate
- Mutants accumulate
Wild type HIV
- More Easily transmissible
- Replicates more efficiently
- Returns once medications are stopped*
- Overtake mutant virus
Mutants are held in reserve
- Return to overtake wild type virus once medications are restarted
Initial Viremia
vs Secondary Viremia
vs Window Period
Initial viremia leads to infection of lymph nodes
Secondary viremia
- Mononucleosis-like illness
“Window period” - happens AFTER the secondary viremia
Silent viral replication in lymph nodes
Little or no HIV antibodies
From ½ - 3 months (depending on test used)
- PCR: about 1-2 weeks AVERAGE
- Advanced serology tests: 2-4 weeks AVERAGE
- Old serology tests: 3 months AVERAGE
Infectious mononucleosis (mono)
mono is often called the kissing disease. The virus that causes mono (Epstein-Barr virus) is spread through saliva. You can get it through kissing, but you can also be exposed by sharing a glass or food utensils with someone who has mono. However, mononucleosis isn’t as contagious as some infections, such as the common cold.
Symptoms of Mono
what other illness do these symptoms resemble?
Symptoms extreme fatigue. fever. sore throat. head and body aches. swollen lymph nodes in the neck and armpits. swollen liver or spleen or both. rash.
Secondary viremia for HIV presents as mono-like illness
Acute HIV Syndrome
mononucleosis-like illness
- fever, malaise, non-exudative pharyngitis, maculopapular rash (50%), - myalgias, headache, GI distress
- generalized lymphadenopathy, hepatosplenomegaly, oral or vaginal thrush
- lymphopenia then acute lymphocytosis
HIV antibody negative but PCR and antigen positive
1-6 weeks after infection
Lasts up to 3 weeks
Spontaneous resolution
HIV disease progression
Destruction of CD4+ T cells - By CD8+ T cells - By HIV - Bone marrow suppression Reaching of a “set point” of viral copies and CD4+ cells Steady progression of immune destruction
What is the CD4 count for a person that signals SEVERE HIV = AIDs
Anyone over 6 years old with a CD4 count less than 200 is SERIOUS this is considered AIDS
What is the natural history/timeline of HIV disease
you measure progression based on CD4 levels
This is how the progression happens:
- Acute infection = large drop in CD4
- Body recovers
- Asymptomatic infection due to decreasing CD4- based on “set point”
- Once it gets under 200 then its AIDS
Diagnosing HIV
HIV serology
- Screening and confirmatory test in humans > 18 months age
- can’t rely on serology for younger because they still have mothers antibodies
HIV PCR
- Screening and confirmatory test in humans < 18 months age
Viral load Determination of viral copy number Viral RNA numbers Expressed as number of copies/ml blood, or log log 2 = 100 copies/ml log 3 = 1000 copies/ml < log 1.3 = < 20 copies/ml ~ “undetectable” “Undetectable”
What kind of symptoms does HIV lead to?
INFECTIONS Sinopulmonary infections Salmonellosis Meningitis Candidiasis
CARDIOMYOPATHY
HIV-related
GROWTH AND SEXUAL DEVELOPMENT
Delayed
Decrease in testosterone/libido
Osteoporosis
NEUROLOGICAL
Cognitive delay
Encephalopathy
Dementia
RENAL
HIV nephropathy
PSYCHIATRIC
Depression
ADHD
HIV disease GI manifestations
DISORDERS OF THE ESOPHAGUS
⅓ of all AIDS patients have esophageal disease Typical symptoms Dysphagia and odynophagia Esophageal inflammation Ulceration Infectious and noninfectious causes
HIV-associated idiopathic esophageal ulcers
40% of ulcers seen in AIDS
Associated with severe immunosuppression
Likely caused by HIV
Seen in lymphocytes and lamina propria
Esophagoscopic lesions are similar to CMV
Which three pathogens leads to esophagitis in HIV patients?
- Candida esophagitis
- Herpes virus esophagitis
- CMV esophagitis
Types of Infectious Oral lesions from HIV
- Their cause
- painful vs not painful
Cold sores around the outter and inner lips
- Herpes Simplex
Oral Hairy Leukoplakia
- EBV related (not painful)
White patches on the soft palette of the mouth
- Candidiases (painful)
Neoplastic Lesions in HIV patients
Dark oval spots in MANY places: could be on their back, mouth, shins
Caused by Kaposi’s Sacroma
- KSHV or HHV8
- severe immunosuppression
Disorders of the liver in HIV caused by HBV
Hepatitis B and/or Hepatitis C
- Shared routes of transmission
HBV
Chronic HBV infection
- 20% of HIV co-infected people
- 5% of HIV negative people
Spontaneous reactivation seen in AIDS
- 19 times more likely to die if HIV/HBV co-infected*
- Cirrhosis, liver failure, carcinoma
HBV does not influence HIV progression
Disorders of the liver in HIV caused by HCV
HCV liver-related mortality in HIV+ people
- 94 fold risk higher than general population
*HCV may affect progression of HIV
All HIV+ patients should be screened for HCV
- HCV antibody
- HCV RNA PCR
OTHER causes of disorders of the liver in HIV patients
Pharmacological Hepatitis - Protease inhibitors (ritonavir) - NNRTI (nevirapine) - Antimycobacterial drugs (rifampin, rifabutin, INH)
Jaundice
- Protease inhibitors (atazanavir)
- Septra, macrolides
Steatosis
- With mitochondrial toxicity and lactic acidosis
- NRTI (ZDV, d4T, ddI) - Protease inhibitors (ritonavir)
Ritonavir
- Side effects
This is a protease inhibitor
When used for HIV patients can lead to
- Hepatitis
- Steatosis
Diarrhea in HIV patients
Diarrhea
Worldwide major cause of morbidity and mortality in AIDS patients
- 95% of AIDS patients in 3d World
- 72% 10-month mortality (chronic diarrhea)
Causes are MANY
Colitis
Malabsorption
Disorders of the Intestines in HIV caused by bacterial and viral agents
Bacterial SSCYE, Listeria monocytogenes Mycobacterium avium complex Obstructive as well Mycobacterium tuberculosis Obstructive as well Toxin-mediated Clostridium difficile Bacterial overgrowth
Viral
CMV, Adenovirus, Rotavirus, HIV
Other causes of viral gastroenteritis
Infections of the intestines in HIV patients caused by parasitic or fungal pathogens
Parasitic
MANY
Giardia lamblia
Cryptosporidium parvum, Microsporida, Isospora belli, Cyclospora cayetanensis, Entamoeba histolytica
Fungal
Histoplasma capsulatum
Risk factors for disorders of the Intestine in HIV patients
Risk factors Severe immunosuppression Environmental conditions Travel-related exposures MSM
Pharmacological
Most all antiretrovirals
Antibiotics
Immune-mediated
Inflammatory bowel disease
Immune Reconstitution Syndrome
Celiac disease
Neoplastic
Idiopathic
- 50% of chronic diarrhea
HPV stands for
Human Papilloma Virus
HPV disease
Important to have HIV positive patients be vaccinated against HPV*
Cervical papillomas
Proctitis [inflammation of the lining of the rectum]
Sexually transmitted:
Chlamydia trachomatis
Neisseria gonorrhea
Treponema pallidum
HPV disease
Anal condillomatosis
Cervical/Anal cancer
AIDS is….
Opportunistic infections: Pneumocystis jiroveci Toxoplasma gondii Candida esophagitis/moniliasis Cytomegalovirus Disseminated varicella zoster Mycobacterium avium intercellulare JC virus/Progressive multifocal leukoencephalopathy
Other infections Salmonellosis Crypto/microsporidiosis Isospora belli Giardia lamblia Neoplastic transformations HHV-8:Kaposi sarcoma, Castleman disease CNS lymphoma Other manifestations of HIV Cardiomyopathy, nephropathy (proteinuria, nephrotic syndrome), hepatitis, wasting syndrome
What is the outcome of having HIV disease
Death
HIV: initially considered to be 100% lethal
Chronic disease
- HAART
The course of the disease has been altered
prior to HAART: median duration was 7.8 years
after HAART: median duration > 15 years
List some bacterial opportunistic pathogens for HIV
Pneumocystis jiroveci
Mycobacterium avium complex
Mycobacterium tuberculosis
Cryptococcus neoformans
List some viral opportunitic pathogens for HIV
CMV
Retinitis, uveitis, retinal detachment, visual loss, pneumonitis, disseminated
HSV, VZV
Reactivation
Erosive or extensive disease
HHV-8
Kaposi’s sarcoma
HBV, HCV
Progressive cirrhosis
JCV
Progressive multifocal leukoencephalopathy
List some parasitic pathogens for HIV
Toxoplasma gondii
- only ONE we’ve learnt
Pneumocystis jiroveci ** and HIV
- Treatment
Most frequent opportunistic pathogen in AIDS patients
25 – 60% of all
Fever, cough, SOB
HYPOXIA
10 –20% mortality
Can involve extra-pulmonary areas as well (liver)
TREATMENT: Primary Prophylaxis: Septra po - For all HIV+ children < 1 year old regardless of CD4 count - For older children and adults: When CD4 < 200 (or < 15% of total lymphocyte count)
Treatment:
Septra (IV or po)
Systemic corticosteroids
Supplemental oxygen
Secondary prophylaxis
Septra
Until CD4 > 200 for 3 months
Mycobacterium avium complex and HIV
- treatment
example of bacterial opportunistic pathogen
Mycobacterium avium intracellulare - Among others Disseminated disease based in the gastrointestinal tract and reticuloendothelial system Pulmonary disease Fever and weight loss
TREATMENT
Primary Prophylaxis Azithromycin or clarithromycin For children < 6 years old Severe immunosuppression For people > 6 years of age CD4 < 50 cells
Treatment
Macrolide + rifabutin
Other second-line drugs
Secondary prophylaxis
Macrolide + rifabutin
Until CD4 > 75 for 3 months
Mycobacterium tuberculosis in HIV patients
- IMPORTANT distinguishing outcome from this type of infection*
Acts like an opportunistic bacterial pathogen
Mycobacterium tuberculosis Lymphadenopathy Pulmonary disease Intra-abdominal disease THE GREAT IMITATOR
HIV patients can transmit this to others much easier than non-HIV patients
LEADING CAUSE OF DEATH WORLDWIDE FOR HIV INFECTED PATIENTS
Infection can occur at ANY time in the immune history of a patient with HIV
ALL patients with TB should be screened for HIV
ALL HIV patients should be screened for TB
What is the leading cause of death worldwide for HIV patients?
mycobacterium tuberculosis infection
What should all patients with HIV be screened for?
TB!
and all patients with TB should be screened for HIV because this is the leading cuase of death worldwise for HIV patients
ALL HIV POSITIVE patients need HEP B, HEP C and TB SCREENING, because it will affect the way you move forward with this patient
will be on exam
Cryptococcus neoformans in HIV patients
- symptoms and conditions it leads to
- Treatment
Acts as opportunistic fungal pathogen
Cryptococcus neoformans: MENINGITIS* Raised intracranial pressure Necrotizing lymphadenitis (mediastinal, cervical) Necrotizing pneumonitis Skin abscesses
Treatment: Amphotericin B + Fluconazole IV Followed by fluconazole po for ?weeks to months Secondary prophylaxis Usually lifelong
Which opportunistic pathogen is known to lead to meningitis in HIV patients?
Cryptococcus Neoformans
this is a yeast (fungus)
Examples of Opportunistic Viral Pathogens in HIV
CMV
Retinitis, uveitis, retinal detachment, visual loss, pneumonitis, disseminated
HSV, VZV
Reactivation
Erosive or extensive disease
HHV-8
Kaposi’s sarcoma
HBV, HCV
Progressive cirrhosis
JCV
Progressive multifocal leukoencephalopathy
Opportunistic Parasite in HIV
- how is it transmitted
- symptoms
- Is there a treatment?
Toxoplasma gondii Parasite Consumption of raw beef Consumtion of organism from cat feces Encephalitis, seizures, disseminated CNS lesions (ring enhancing)
Treatment:
JUST KNOW THERE IS ONE. [Sulfadiazine + pyrimethamine + folinic acid (leucovorin)]
Secondary prophylaxis. just know there is one
HIV Therapy
JUST KNOW: HAART: Highly Active AntiRetroviral Therapy
- combination therapy with NRTI, NNRTI, PI, FI, Integrase Inhibitors, and/or CCR5 receptor antagonists
aim:
reduction of HIV viral load to undetectable levels
elevation of CD4 T-helper lymphocyte counts
standard of care
“Undetectable = Untransmissible”.
[NRTI = inhibits RT that’s a nucleoside NNRTI = inhibits RT that’s a NON-nucleoside ]
Which HIV treatment is the backbone of HIV therapy
Integrase Inhibitors & CCR5 coreceptor antagonists
Integrase inhibitors
Prevent integration of pro-viral DNA into human chromosomal DNA
[i.e. Cabotegravir – once monthly injection (depot delivery)]
Coreceptor antagonists
Prevent binding of HIV on to human cells
“Boosting” the antiretrovirals
Inhibition of liver cytochrome p450 enzymes that metabolize some antiretrovirals (protease inhibitors, elvitegravir)
Aim: increase levels of antiretrovirals in the blood and tissues for maximum efficacy
When to treat HIV
on exam*
All HIV+ children < 1 year of age
All HIV+ pregnant women
All symptomatic HIV+ patients regardless of CD4 count
All patients with moderate immune suppression regardless of symptoms
CD4 count <350 cells/ml
Pendulum has swung:
Start as soon as possible after diagnosis and regardless of CD4 count to preserve immune function and prevent chronic inflammatory damage (to heart, blood vessels etc).
Viral load log > 5.0
Goals of HIV management
- What treatments do we use for these goals
Decrease Viral Load to undetectable levels Improve immunity Preserve immunity Prevent toxicity Treat/prevent OI Maintain well-being of the patient PREVENT TRANSMISSION
treatments: HAART Monitor CD4 and VL every 3 months if patient is stable OI prophylaxis Vaccinations Multidisciplinary approach
When to STOP HIV treatment?
Never unless there are life threatening side effects
Treatment interruptions are not recommended anymore
Many patients end up with bacterial infections (e.g.. meningitis) as their immune systems weaken and CD4s start to drop < 350 cells/mL
Adult vs Child HIV
- CD4 counts
- Viral load
just know for adults, CD4 <200 = AIDS
for children it is MUCH higher, CD4<750 = AIDS
Neonatal HIV: initial higher viral load
May take longer to become undetectable
Clinical difference in CHILDREN with HIV vs adults?
Children:
- Growth failure
- Progressive neurodevelopmental deterioration
- LIP; lymphoid interstitial pneumonitis (lung) = HYPOXIA
If a child presents with hypoxia and has a NORMAL immune system count, consider ruling out__ and ruling in___
r/out: bacterial infection
r/in: HIV (LIP manifestation)
[LIP = Lymphoid Interstitial Pneumonitis]
Opportunisitc infections in HIV+ children
*Pneumocystis jiroveci pneumonia
[Peak incidence 1-2 months of age
Neonatal TMP/SMX prophylaxis starting at 1 month age until HIV is under control and CD4 counts are above severe immune suppression levels for age > 6 months]
Risk of HIV progression in infants?
Children < 12 months age
7-fold chance of developing AIDS or death within 12 months
Even at normal CD4 levels
this is why ALL babies under 1 get put on ART
Vaccinations for HIV+ children
Vaccinations:
In severely immune-suppressed
- Vaccines not effective
- Deferral until reconstitution
- Re-immunization once reconstituted
- Boosters
Live vaccines (MMR, Varivax, yellow fever, oral typhoid, oral polio, intranasal influenza)
Contraindicated until CD4 rises to normal levels
BCG is an absolute contraindication
**You CAN’T give LIVE vaccines: because you will CAUSE disease in these people. You must wait until they are immune reconstituted.
How do children contract HIV
Vertical transmission
Mother-child transmission
Perinatal exposure
- especially intrapartum
- postpartum (through breastmilk)
- less so in utero
Blood product transfusion
Sexual abuse
In the adolescent years
- sexual intercourse
- IV drug use
Which type of HIV is more transmissible?
HIV-1 15-45%
highest in sub-Saharan Africa
HIV-2 1%
How can you decrease HIV transmission during pregnancy?
Giving ART to a pregnant women DOES decrease transmission significantly.
Implementation of universal prenatal HIV counseling and testing
Antiretroviral treatment and prophylaxis
Scheduled C-section (in some cases)
Avoidance of breastfeeding*
Now, the rate of transmission in the developed world:
Less than 2%
What are the two HIV testing approaches for pregnant women
Opt-in:
Asking pregnant mother what tests (includes HIV screening) she would want performed on her. (nope)
Opt-out:
Telling pregnant mother that a certain number of tests will be done and asking her what tests she would NOT want performed on her. (YES)
Both options work as long as there is adequate counseling by the caregiver.
4 areas of Perinatal Exposure Prevention
Since we know that the majority of children with HIV are infected around birth, prevention can be focused on four areas:
- reducing viral load in HIV-infected mothers
- reducing exposure to HIV during delivery
- preventing infection during or after exposure
- reducing exposure to HIV during breastfeeding
Main tool for reducing HIV transmission perinatally
Main tool for reducing transmission:
Universal informed opt-out screening for HIV infection in all pregnant women
TReatment for mother vs child
Mother (goal: VL < 20):
HAART
If already on HAART when gets pregnant:
- Continue
ARVs that cross the placenta easily should be a part of the maternal regimen (ZDV, 3TC, TDF etc)
Some guidelines state to give IV ZDV during delivery
Consider C-section if viral load is > 1000 copies/mL
Baby (goal: no infection): Oral ZDV X 4 weeks May add a second/third drug to help reduce transmission NO breastfeeding Septra prophylaxis can be started at 1 month Until HIV is ruled out HIV PCR testing At least 1 month and 4 months
Why isn’t septra prophylaxis given to infants in canada from HIV+ mother?
because prophylaxis is ideal in situations where the baby cannot be monitored closely. i.e. in US where you pay for meds, mothers may not want to come back in for check ups so its safer to give prophylaxis.
this is not necessary here.
What you might seen in emerg with HIV patients
Bacterial sepsis Severe resp disease - LIP Acute neurologic deterioration Diarrhea and Dehydration
What shouldn’t you do as a doctor when trying to prevent maternal-child HIV transmission?
A. Offer antiretrovirals to both the pregnant mother and newborn
B. Consider an elective C-section if the mother has a detectable viral load near delivery
C. Discourage breastfeeding. Encourage formula feeding.
D. Encourage breastfeeding. Discourage formula feeding.
E. Try to have the mother’s viral load be undetectable prior to delivery.
You SHOULD NOT do this: D. Encourage breastfeeding. Discourage formula feeding.
Highest to NO RISK infectious materials for HIV
Highest risk
concentrated lab HIV, blood, any fluid contaminated with blood
Intermediate risk
semen, vaginal secretions, CSF, amniotic fluid, pleural/pericardial/peritoneal/synovial fluids, human milk
No risk
saliva, urine, feces (diarrhea), tears, sweat, sputum, mucus, vomitus
Effectiveness of Post Exposure Prophylaxis for HIV
PEP has been shown to significantly decrease the risk of transmission from mild, moderate and even from a higher risk events. The mitigation obviously depends on risk of event.
Works only if given as soon as possible after the event up to 48 hours (although then you are cutting it close).
Has to be triple drugs
Given for 28 days
There has never been a documented transmission from a non-occupational needlestick injury.
Repeated exposures do not warrant PEP. Perhaps PrEP works best here.
U = U
“Undetectable VL = Untransmissible HIV”
Makes sense and removes decades long stigma associated with HIV
Allows discordant couples to have sex without barrier contraception
Conception for example (Swiss are very much following this)
Breastfeeding? Although there is Paediatric concern as U in blood may not = U in breast milk.
90-90-90 goals
90% of all people with HIV knowing their infection status
90% of these people to get access to treatment
90% of these people to achieve “suppressed” (undetectable) viral loads
What are the common bacterial infections for
gram +
gram -
Gram +
Staphylococcus
Streptococcus
Corynebacteria
Gram -
Pseudomonas
Neisseria
Direct infection of skin and adjacent tissues
Cutaneous disease due to effect of bacterial toxin
Honey Coloured crust around lips and fingers is called what?
- DIagnosis
- highly contagious in
Erythmatous Macule
diagnosis: Impetigo
a mild infection that can occur anywhere on the body. It most often affects exposed skin, such as around the nose and mouth or on the arms or legs. Symptoms include red, itchy sores that break open and leak a clear fluid or pus for a few days.
Highly contagious in children
Honey Coloured crust around lips and fingers is called what?
- DIagnosis
- highly contagious in
Erythmatous Macule
diagnosis: Impetigo
a mild infection that can occur anywhere on the body. It most often affects exposed skin, such as around the nose and mouth or on the arms or legs. Symptoms include red, itchy sores that break open and leak a clear fluid or pus for a few days.
Highly contagious and primarily in children
Flaccid, transparent bullae → rupture leaving shiny, dry erosion with no surrounding erythema
- Diagnosis
- What are the two types?
Impetigo
two types: Bullous and Nonbullous
Impetigo Non Bollous
- which type is most common
- which organisms are most common
- diagnosed with
- Treated with?
Nonbullous most common cause:
Organisms:
S . Aureus (gram +)
Group A strep (less common) (gram +)
+ culture from exudate under crust
Treat with topical or oral antibiotics
Impetigo, Bullous type
- which organisms
- presentation
- treatmente
Bullous : S . aureus ONLY
Cleavage at granular layer due to effect of bacterial toxin (looks like red bubbles on the skin)
Treat with topical and oral antibiotic
Impetigo
- who does it effect
- what are the two types
- What are the common organisms
- Clinical presentation
- treatment
Primarily in children
- Two types: non bullous and bullous
- S . Aureus (NB+B) or Group A strep (NB)
Direct infection of skin and adjacent tissues
Cutaneous disease due to effect of bacterial toxin
Highly contagious
Treat with topical and/or oral antibiotics
Bacterial Folliculitis
- common pathogen
- treatment
Superficial infection of hair follicle usually due to S . Aureus Treatment: antibacterial wash antibiotic creams if widespread can use oral antibiotic
Furuncle, Carbuncle, Abscess
- define each
- organism
Furuncle : deep-seated tender nodule of hair follicle
Carbuncle : coalescing of adjacent furuncles with multiple draining sinuses (typically involves nape of neck or back of thighs)
Abscess : inflamed walled-off collection of pus
Typically due to S . Aureus
Depth of infection determines presentation
Treatment for Furuncle, Carbuncle, Abscess
Treatment
Simple furuncle : warm compresses and topical antibiotics
Fluctuant furuncle or abscess: incision and drainage
Oral antibiotics if:
Located near midface or external auditory canal
Recurrent or recalcitrant
Very large
Ecthyma
Deeper form of nonbullous impetigo with ulceration
Caused by GAS [group A strep] but quickly contaminated by S. aureus
Treatment: oral antibiotics
Erysipelas
Superficial type of cellulitis with significant dermal lymphatic involvement
Typically due to GAS
Treatment of choice: oral antibiotics
Cellulitis
Infection of the deep dermis and subcutaneous tissue
GAS (2/3 of cases) , S.aureus (1/3 of cases)
Treatment: oral/ IV antibiotic
typically presents as unilateral and lower extremity
i.e. one red leg
Necrotizing Fasciitis
Rapidly progressive necrosis of subcutaneous tissue and fascia
GAS, but typically mixed infection with 30% mortality rate
Treatment: extensive surgical debridement
presents: tender, erythematous tense plaques
Perianal Streptococcal Disease
Perianal GAS infection
Obtain both throat and perianal culture;
treat with oral antibiotics
Erythrasma presentation organism diagnostic tool treatment
Presents as well-demarcated red-brown macules/patches with fine scale and wrinkling in intertriginous areas;
organism: CORYNEBACTERIAL INFECTIONS
gram-positive rod-shaped bacteria
Diagnostic: Wood’s lamp, bright coral-red fluorescence due to porphyrin production
Treatment: topical antibiotic clindamycin, erythromycin
Green Nail Syndrome
- organism
- environment
- Treatment
PSEUDOMONAS
GRAM-NEGATIVE
grows well in aqueous environment,
has ability to produce variety of pigments
Treatment: trim nail, acetic acid soaks, topical antiobiotics
Hot Tub Folliculitis
- type of organism
- environment
- Treatment
PSEUDOMONAS
GRAM-NEGATIVE
grows well in aqueous environment,
Pseudomonal Folliculitis
Self-limited in immunocompetent person
What are the two types of bacterial infections caused by Pseudomonas
Hot Tube Folliculitis
Green Nail Syndrome
Acute Meningococcemia
- Where does the infection happen
- Organism that causes it
- Treatment
Acute and potentially life-threatening infection of the blood vessels
Caused by Neisseria meningitidis , gram-negative
Treatment: high dose IV antibiotics
Scarlet Fever
- Clinical Presentation
- organism
- demographic
- Treatment
Presents
sore throat, headache, fever
tiny pink papules on erythematous background (sandpaper-like),
after the 2nd or 3rd day scattered, swollen, red papillae give the ‘strawberry tongue’ appearance, palatal petechiae,
Perioral/ chin pallor in severe cases face affected
linear petechial streaks along body folds
Diffuse exanthem from GAS pharyngitis
mainly in children
Treatment: oral antibiotics
Primary Herpetic Gingivostomatitis - organism - demographic - presentation treatment
Herpes Simplex Virus 1 and 2 (HHV1, HHV2)
Primary infections:
typically in children
abrupt onset of erythematous, friable gingiva
painful vesicles clustered on oral mucosa, tongue, lips, and/or perioral
skin → vesicles rupture, leaving small ulcers with characteristic gray base; ± pharyngitis, tonsillitis, difficult to eat and swallow, enlarged lymph nodes, fever, and anorexia
Treatment:
Hydration, pain control, hospitalization
Neurotropic virus which hides in the dorsal root ganglion until reactivation
Primary Genital Herpetic infection
presents with constitutional symptoms and PAINFUL grouped vesicles in genitalia → progress to pustules, crusting and exquisitely tender ulcers,
more severe and prolonged than recurrent infection
± painful lymphadenopathy, cervicitis, urethritis, proctitis
Acyclovir 200 mg five times a day x 7-10 days or 400 mg TID ( 15/mg/kg five times a day)
Valacyclovir 1 g BID for 7-10 days
Famciclovir 250 mg TID for 7-10 days
Recurrent Herpetic Infections
Herpes labialis:
Genital herpes:
[Herpes labialis. most common HSV-1 manifestation
triggered by pyrexia, stress, sunburn, and/or trauma;
prodrome (pain, burning, tingling) may precede eruption;
grouped vesicles on erythematous base which typically evolve into pustules and then painful ulcers
± prodrome followed by grouped vesicles → pustules → ulceration]
Eczema Herpeticum
- organism
- presentation
Herpes Simplex Virus 1 and 2 (HHV1, HHV2) infection
Disseminated form of HSV mainly seen with atopic dermatitis
can also occur when there are other reasons for breakdown of the skin barrier
Herpetic Whitlow, HErpes Gladiatorum
a viral condition where small blisters form on the fingers and the fleshy area around the fingertips. These sores or blisters are often painful and develop after direct contact with a contagious sore. The herpes simplex virus (HSV) causes this condition.
- noted in wrestlers, involves extramucosal sites typically over face, neck, or arms
Diagnosis of Herpes Virus
Tzanck smear shows multinucleated epithelial giant cells – does not differentiate between HSV and VZV
Viral culture
direct fluorescent antibody (DFA)
Viral PCR
Histology skin biopsy
Treatment for Primary Herpes Recurrent Herpes Eczema Herpeticum Herpetic Whitlow Herpes Gladiatorum
Primary herpes: Oral / IV antivirals Pain control Recurrent herpes: Oral / topical antivirals Suppressive treatment Eczema herpeticum IV antivirals Herpetic whitlow Herpes gladiatorum Oral antivirals
Varicella- Zoster Virus (chicken pox)
- treatment
- demographic
- presentation
(isolation) Usually more severe in adults or immunocompromised patients and can be life-threatening in complicated cases Oral/ IV antivirals (24H after onset) VZIG (within 4 days post exposure) Prevention: vaccine - Resolves 1-3 wks but may leave scars
presentation: Prodromal pain/paresthesias grouped, painful erythematous macules/papules along single sensory dermatome → vesicles/bullae → hemorrhagic crust and dry over 7–10 days
Lesions infectious until dry
Reactivation of VZV
After initial varicella infection, virus lies dormant in spinal dorsal root ganglion until reactivation herpes zoster
Treatment: Oral antivirals
Prevention: vaccine
Zoster Complications
post-herpetic neuralgia (PHN)
Scarring
Secondary bacterial infection
meningoencephalitis
Ramsay–Hunt syndrome (ear canal/auricle/tympanic membrane involvement with painful vesicles, facial paralysis/paresis, ipsilateral hearing loss)
Ocular blindness (lesions on tip of nose possible ocular infection nasociliary nerve involved, which is a branch of the ophthalmic nerve)
Which sites are used to measure body temperature?
Which sites are the most accurate measure of body temperature?
Ear, mouth, rectal, pulmonary, axillary
Gold Standard: Pulmonary Artery Catheter
- invasive, limited availability
BEST estimate: rectal
Which method taking temperature is notoriously inaccurate and unreliable
Axillary! the pits!
Normal Body Temperature
A range that fluctuates over the day and varies in different populations
Healthy individuals aged 18-40 years old
Mean oral temperature 36.8C ± 0.4C
Lower levels tended to be at 6 AM
Highest values between 4 and 6 PM
Normal variation of 0.5C throughout the day
99th percentile in healthy individuals was 37.2C at 6AM, and 37.7C at 6PM.
factors that lead to variable temperature readings
Fertile women
- Lower AM temp 2 weeks prior to ovulation
- Temp then rises by 0.6C until ovulation
Postprandial state Pregnancy Endocrinologic dysfunction Age - Fixed variation in childhood - Inability to mount fever in even extreme infection in the elderly
Nutritional status (perhaps) - Inability to mount febrile response in catabolic, malnourished states
What temperature is Fever?
- define fever
38.3.. 38.0
Fever
fever is a regulated rise in core temperature due to a corresponding rise in the thermoregulatory set point in response to a physiologic threat to the host
define Hyperthermia
UNregulated increase in core temperature in which inflammatory cytokines play only a minor role
characterized by a sustained elevation of core temperature lacking the diurnal fluctuations characteristic of both fever and normal body temperature
does not respond to antipyretic drug therapy
Hyperpyrexia Definition
a fever greater than 41.5C
Extreme elevation of thermoregulatory center set point
severe infections
CNS hemorrhages
Limit of fever by endogenous central anti-pyrogens
Causes of Hyperthermia
Heat Stroke
- Exercise in excessive heat/humidity
Illicit Drug Induced
- PCP, ecstacy/MDMA, LSD, amphetamines, cocaine, lithium
Neuroleptic Malignant Syndrome (NMS)
- Antipsychotics, withdrawal of dopaminergic agent
Toxidromes/ODs/Drug Fever
- SSRIs, MAOIs, TCAs, anticholinergics, salicylates, antihistamines, antiparkinsonian drugs, diuretics, cardiovascular meds, ABX
Malignant Hyperthermia
- Anesthetics, succinylcholine
Endocrinopathies
- Thyrotoxicosis, pheochcromocytoma
CNS Insults
-Cerebral hemorrhage, status epilepticus, hypothalamic injury
3 Components of Febrile Response
Endocrine
- Increased: glucocorticoid production, GH secretion, aldosterone secretion, acute-phase proteins
- Decreased: vasopressin secretion, levels of circulating divalent cations
Autonomic
- Shift of blood flow from cutaneous to deep circulatory beds
- Increased heart rate and blood pressure
- Decreased sweating
Neurobehavioural
- Shivering, search for warmth
- Anorexia, malaise, somnolence
Physiologic Responses in Fever
increased cardiovascular and metabolic demands
increased oxygen (O2) consumption
increased heart rate
increased cardiac output
- Heart rate, blood pressure, and cardiac output become elevated to increase O2 delivery and meet tissue needs
elevated serum catecholamine production
increase in body temperature on average by 1-2oC
increase in heat production by the liver
- For each 1oC increase in body temperature, there is a 13% increase in O2 consumption without shivering
- Shivering can also occur during fever, increasing oxygen consumption to 100% to 200% above base-line values
Which infection causes fever in a Quartian and Tertian pattern?
Malaria
Why suppress a fever?
There is no valid reason to do so. it is a normal physiologic response
unless it gets REALLY bad
Define Fever of Unknown Origin
Classic Definition
- Temperature >38.3C on several occasions
- Duration of fever >3 weeks
- Failure to diagnose despite 1 week of inpatient evaluation and investigation
New Paradigm types of FUO
- Classic FUO
- Nosocomial FUO
- Neutropenic FUO
- FUO associated with HIV infection
Nosocomial FUO
Nosocomial
Hospitalized, acute care, no diagnosis of infection when admitted
3 days under investigation
Neutropenic FUO
ANC <500/ul or expected in 1-2 days
3 days under investigation
Empiric antibiotic coverage typically initiated early
For which type of FUO is empiric antibiotic coverage typically initiated early?
Neutropenic FUO
HIV Associated FUO
Confirmed HIV positive
3 days under investigation, 4 weeks as outpatient
New Paradigm vs Classic FUO
All require temperatures of at least 38.3C on several occasions
All require 2 days of microbiology cultures
Differ in subtle definitions
Will consider Classic FUO in adults for this presentation
What has changed through out the years that helped diagnose fever and prevent them from being categorized as FUO
Use of antibiotics, as well as novel invasive and non-invasive technologies has helped diagnose more patients
FUO, fever in a returned traveller is ___ until proven otherwise?
Malaria (P falciparum)
Causes of FUO
Infectious causes
Neoplastic causes
Inflammatory/Connective Tissue Diseases
Other and Unknown
Which tumorals were emphasized to lead to FUO
Malignant disease:
Hodgkin’s lymphoma, Non-Hodgkin’s lymphoma, leukemia,
among general organ cancers
Examples of Inflammatory causes of FUO
Increasingly the cause of noninfectious FUO
Autoimmune, systemic rheumatologic, vasculitic diseases, auto-inflammatory
- Still’s disease, Polymyalgia rheumatica
- SLE, RA
- vasculitides: GCA/TA, GPA, PAN
- Granulomatous disease
Sarcoidosis, Crohn’s disease, granulomatous hepatitis
FMF, TRAPS
Considerations in the elderly for FUO
Multisystem disease is most common
- Temporal arteritis / Giant cell arteritis
- polymyalgia rheumatica
Infectious cause
- Leading is mycobacterial disease
Neoplastic disease
- Colon cancer
Thrombosis
Prognosis of FUO
Outcomes in cases of FUO are related to etiology
No source – excellent prognosis, especially:
without B-symptoms
With a negative PET-CT
Spontaneous recovery 51-100 %
Persistent fever in 0-30 %
stage 1 of FUO work up
Confirm true fever Diary of fever as outpatient Pattern offers little help in most cases If possible, stop medications Fever stopping in <3 days may be a drug fever
COMPLETE HISTORY - OCCCCUPATION sex IVDU travel
CT scan for FUO
Evidence – favours recommendation
Especially CT Abdo
High diagnostic yield – should be one of first tests
Can identify 2 common causes
- Occult intra-abdominal abscesses, neoplasm
Retrospective analysis
- Diagnostic yield of 19%
- Good sensitivity
Which type of Nuclear Medicine Scan is more favoured to diagnose FUO
- what are other types
Evidence – favours recommendation to use Nuclear med scans*
PET scen has high sensitivity and specificity
other options:
Gallium scan
Technetium scan
Indium scan
What diagnostic tests are recommended for FUO based on evidence
which is NOT
CT scan Nuclear Med scan (PET) Echocardiogram Liver biopsy Temporal Artery biopsy Duplex Doppler Scans (examines DVT)
NOT recommended:
Bone Marrow Biopsy
