Describe the pathogenesis of leprosy.
Compare the Tuberculoid and Lepromatous versions of leprosy
Differ in immune response and clinical findings
Both affect nerves
Least severe form of Leprosy
Cell-mediated Immunity is intact
Skin lesions -> Elevated, sharply defined plaques
Nerve damage -> Decreased sensitivity to sharp/dull, hot/cold
Acid-fast is negative
Lepromin skin test (like PPD) is positive
Most severe form of Leprosy
CANNOT mount a Cell-mediated response*
Diffuse infiltration and thickening of skin
*Will see lots of bacilli on acid fast stain
What is the difference of cytokine concentration between tuberculoid and lepromatous leprosy?
Lepromatous shows no Th1 activity, but lots of Th2
Tuberculoid shows both Th1 and Th2 activity
Superficial S. aureus infection that leads to pustule formation.
Pustules break and cause honey-colored crusts
Mostly affects kids
What are the skin infections caused by S. aureus?
Bullous Impetigo (from exfoliative toxins)
Furuncles & Carbuncles
What are the skin infections caused by Streptococcus?
Hot Tub (Pseudomonas) Folliculitis
Caused by Pseudomonas areginosa infection of the hair follicle.
Get it from a dirty jacuzzi
Small red itchy or tender bumps in areas that were covered by a swimming suit.
HSV-1 or 2
Prodrome of localized itching or burning
Grouped vesicles on an erythematous base
Tzanck prep- multinucleated giant cells, direct immunofluorescence, PCR
From Herpes Zoster Infection
Lesions on the tip of the nose -> possible eye involvement
Because of nasociliary branch of the opthalmic division of CN V.
Caused by a DNA papilloma virus that infects epidermal cells.
HPV is transmitted via scratches (Koebner phenomenon).
Flesh colored firm papule or nodule with hyperkeratotic surface.
Caused by a DNA poxvirus that infects epidermal cells.
Smooth dome shaped papules that are often umbilicated.
Common in childhood, can be sexually transmitted, common cutaneous finding in AIDS
Scaly macules, patches, papules and plaques along skin lines
Herald patch is first sign (looks like ringworm)
May come from Herpesvirus subtypes
Infection of the skin from fungal organisms known as DERMATOPHYTES.
Superficial skin infection lesions on head/scalp (capitis), groin (cruris), body (corporus), foot (pedis)
diagnosis: KOH, culture
Candida albicans grows in moist environment
Infection of the epidermis with inflammation
Surrounding satellite papules are typical
diagnosis- KOH, culture
What are mycosides? And what is their relationship to M. tuberculosis?
Remember "Mike the surfer"
Mike - mycosides
WAXing - waxD -> adjuvant that activates protective immune response
SUrfboard - Sulfatides -> inhibit phagosome from fusing with lysosome
CORD - cord factor -> Virulence factor that allows bacteria to grow in cords
Pathogenesis of Tuberculosis
1. Inhalation of droplet -> middle and lower lung (highest air flow)
2. Reaches alveoli and taken up by Macrophages, where they evade killing and multiply
3. Get to regional Lymph Node
4. Multiplication is stopped with Cell-Mediated Immunity -> activated macrophages kill -> local destruction and necrosis of lung tissue
5. Necrotic tissue becomes the center of a granuloma
6. Some bacteria survive inside granuloma and can grow again
What are the symptoms of primary tuberculosis?
Chest X-ray showing -> Hilar Adenopathy, Transient infiltrates, Pleural effusion
PPD test -> can tell 1-3 months after infection
What happens during latent tuberculosis?
Bacilli remain dormant but viable within the granuloma (may have calcified)
No symptoms and not infectious
Chest X-ray shows an "old granulomatous disease"
What is the difference between a Ghon focus and a Ghon complex?
Ghon focus is a small calcified tubercle in the middle or lower lung
Ghon Complex is a focus + calcified perihilar lymph node granulomas
How do you get reactivation of tuberculosis?
Latent infection can get reactivated
Leads to -> cough, hemoptysis, fever, night sweats, weight loss ("consumption")
Focal or widespread pneumonia
Can get dissemination to other tissues (Pleural cavity, pericardium, lymph node, kidney, joints)
Degeneration of the vertebral bodies and intraverterbral disks by extrapulmonary tuberculosis
A swelling of the lymph node (usually cervical) because of extrapulmonary tuberculosis
Small millet-seed sized granulomas that are disseminated all over the body due to extrapulmonary tuberculosis.
Usually happens in elderly and kids
How do you diagnose tuberculosis?
Clinical syndrome -> via patient history
PPD skin test ->Delayed-type hypersensitivity reaction
QuantiFERON TB Gold: Interferon gamma release assay
MOST IMPORTANT => Clinical specimen (AFB stain and culture*)
- Sputum, bronchial lavage, tissue biopsy
- Gastric contents
- Lymph node, CSF, urine
*Takes 4-6 weeks to culture on solid & 9-16 on liquid
How do you read a PPD test?
Read 48-72 hours after injection
Measure only induration in millimeters -> size determines infection, depending on patient history
>5 = immunocompromised
>10 = people with high risk of exposure or other disease that could put them at a higher risk
>15 = people with no known risk factors
How can you get a PPD false negative or positive?
Negative -> Anergy -> something that makes the T-cell response abnormal
Positive -> BCG vaccination or non-tuberculous mycobacterial infection
What are the treatment options for tuberculosis?
1. Initial Phase
- Isioniazid, Rifampin, Pyrazinamide, Ethambutol
- Daily for 2 months
2. Continuation Phase
- Isoniazid, Rifampin
- Daily for 4 months
Failure usually due to non-adherence
Patient isolation until non-infectious (AFB smear-negative)
What are the drugs used for tuberculosis?
- Hepatotoxicity - >Risk increases with age, alcohol use
- Peripheral neuropathy -> Vitamin B6 (pyridoxine) helps prevent
- Orange discoloration of urine, contact lenses
- Optic neuritis
What is Runyon grouping?
Classification system of non-tuberculoid mycobacteria
1. Speed of growth
2. Pigmentation in the Presence/Absence of light
Rapid Growing Mycobacteria
Slow Growing Mycobacteria
NON-CHROMOGENS-> No pigment
M. avium complex
PHOTOCHROMOGENS - pigment only with light
SCOTOCHROMOGENS -> pigment with and without light
Mycobacterium avium-intracellulare (MAI)
A major systemic infection in AIDS patients
Infection occurs when T-cell count is VERY low and rapidly disseminates
Chronic lung disease (bronchiectasis)
Cavitary, nodular disease
Leads to a chronic wasting illness and watery diarrhea
Anti-parasitic drug -> especially against worms
From infection by types 8, 19, and 37 adenovirus
Subepithelial corneal infiltrates common
Preauricular lymph nodes common
Duration: 7-14 days
Can get Ag-Ab complexes deposited after acute infection
Caused by enterovirus and coxsackieviruses
Unilateral or bilateral
May be associated with prodromal symptoms
Confluent subconjunctival hemorrhage
Herpetic viral conjunctivitis
Primary infection at any age
Unilateral with Vesicular skin lesions
Corneal involvement with classic dendrite
Keratitis may worsen with topical steroids
Uveitis may be present
Recurrences are common
What are the organisms that cause ocular infections?
- Adenovirus, Coxsackie, HSV, VZV, CMV, RSV
- Strep, Staph, Pseudomonas, Neisseria, syphilis, borrelia (Lyme disease), Chlamydia (Trachoma)
- Tuberculosis, Leprosy, atypical forms
- Mucormycosis, candida, others
PROTOZOAN & NEMATODES
- Acanthamoeba, Filariasis, Toxoplasmosis, Toxocara
What are the types of delivery of ophthalmic drugs?
Commonly used agents: vancomycin, cephalosporins, oxyfloxacins
Getting into eye
Addressing the eye, secondary to systemic disease
What is a niche difference between M Tb and other NTM's?
M Tb is ONLY a human pathogen -> no animal resevoir
Other NTM's have animal and environmental resevoirs
What is the interaction between HIV and Tb?
HIV reduces cell mediated immunity -> can make Tb reactivate and symptoms worse
An cluster of cells in an organized immune response
Langerhans giant cells (fused macrophages)
Caseating necrosis in center (can still have live pathogen)
Two-step Testing of Tb
Use two-step testing for initial skin testing of adults
who will be retested periodically
If first test positive, consider the person infected
If first test negative, give second test 1-3 weeks
If second test positive, consider person infected
If second test negative, consider person
What is a consequence of lacking Th1 function in Leprosy or Tuberculosis?
Without Th1 -> you get LOTS of Th2
Leads to stimulation of B-cells -> a high amount of antibodies
And suppression of Macrophages by IL-10 from Th2
What is the immune response to helminth infection?
1. Ag is presented to Th2
2. Th2 releases:
- IL-4 -> stimulates isotype switch to IgE
- IL-5 -> stimulates Eosinophil degranulation
3. Mast cells stimulate smooth muscle contractility to expel helminth
Hyper-IgE recurrent infection syndrome -> rare autosomal dominant disorder characterized by
INFECTIONS (No neutrophil recruitment)
- recurrent and often severe pulmonary infections
- staphylococcal abscesses
- mucocutaneous candidiasis
OTHER CLINICAL CHARACTERISTICS
- abnormalities of bone and connective tissue
TYPES: Plaque type, inverse, guttate, erythrodermic, pustular
1. Primary lesion
- erythematous plaques
- silvery scale
2. Nail pits
3. Auspitz sign -> pinpoint bleeding if you remove scale
Can give Anti-depressants to deal with stress
Acute, severe, usually fatal nonspecific hemorrhagic infarction and necrosis of the skin that occurs during infection
Usually Group A Strep
- Also S. aureus, Pneumoccocus, Vibrio, Meningococemia, Varicella
Disseminated Intravasular coagulation (DIC)
What bacteria are the most problematic in terms of resistance?
*Know the ESKAPE mnemonic
S. aureus (MRSA)
Acinetobacter -> #1 resistance to all agents
ESBL (E. coli, Enterobacter)
What are the symptoms of SLE?
Remember the mnemonic, MD SOAP BRAIN. (need 4 out of 11)
Grouped pruritic vesicles and papules, often on elbows, knees, and buttocks
Often associated with gluten-sensitive enteropathy (Celiac disease)
Noninfectious non-caseating granulomas infiltrating tissues
Affects primarily skin, lungs, eyes
Cutaneous lesions can be papules, patches, or plaques
Red-brown papules and plaques
"Apple-jelly" on diascopy
Stages of Lupus Perino
I -> lymphadenopathy
II -> lymphadenopathy + pulmonary infiltrates
III -> JUST pulmonary infiltrates
IV -> pulmonary fibrosis
A hereditary tendency to develop allergies to food and inhalant substances
Usually starts after age 2mo
Infant (diaper area, head, flexor/extensor surfaces)
- Antecubital & politeal fossa
- Face, neck, and upper chest
How do you treat rosacea?
Use Tetracyclines or Metronidazole
Triggered by heat, alcohol, sunlight, spicy food
NEVER use topical steroids!!
Caused by mite, Sarcoptes scabei
- Erythematous excoriated papules -> Intensely itchy
- Worse at night
- CONTAGIOUS -> Spreads to household members
- Wrists, web spaces
- Intertriginous areas, genitals
Found in variety of people (area, SES)
Live on hairs of head and feed on scalp
Pruritus on the scalp
Linear excoriations at the periphery of the hair area
Permethrin Cream rinse, Lindane Shampoo
Ivermectin (for resistant bugs)
Found in the homeless
Pruritus and excoriations
Nits are found in seams of clothing, not on human hairs
Can be vectors for BACTERIAL PARASITES (Rickettsia & Bartonella)
Crab Lice (aka Crabs)
Spread as a sexually transmitted disease (STD).
Occasionally transmitted by fomites from contaminated clothing, towels, or bedding
Maculae coeruleae (gray to bluish, macules 0.5-1 cm in size)
*Can also be found in mustache, beard, axillae, eyelashes, eyebrows
Blood-sucking insects,5-7 mm -> feed at night
Live wooden floors, furniture, mattresses
Inject anticoagulant- and anesthetic-saliva (WONT FEEL BITE)
What causes allergic reactions to insect stings?
Bee, hornet, wasp
Melittin (protein) cause:
- Degranulation of basophils and mast cells -> releasing 1) histamine, 2) Phospholipase-A, 3) hyaluronidase (enzymes)
Can have range of reactions
Toxic: >10 stings
Anaphylaxis: urticaria, bronchospasm, hypotension
Drug Biotransformation Enzymes
Cytochrome p450 enzymes (CYPs)
- Liver enzyme
- Deficient in Crigler-Najar (Aut rec, can't break down bilirubin -> kernicerus a.k. bilirubin encephalopathy)
- Responsible for metabolizing acetaminophen -> if runs out, get toxicity
How can aminoglycosides cause hearing loss?
Mitochondrial A1555G Mutation
Predisposes carriers to hearing loss when given aminoglycosisdes
Red eye with no pain or decreased vision
The cornea is clear with a good light reflex