Viral Skin Infections and Mycoses Flashcards
Structure and nuclear makeup of Herpes
Herpes is icosahedral and is a linear double stranded DNA
Discuss the general pathogenesis of Herpes
These guys infect mucosal epithelial cells and replicate in the nucleus.
The viral particles bud through nuclear membranes and into the membranes of exocytic vesicles during egress from host cells
Discuss the three types of herpes viruses
alpha - HSV1,2, and VZV - These guys have a short replication cycle and stay latent in sensory ganglia and neurons
Beta - HHV6,7 and CMV - longer replication cycle and the infected cells become larger. This guy hides in monocytes/macrophages, lymphocytes and endothelial cells
Gamma - HHV-8 and EBV - Infect both epithelial cells and lymphocytes, are lymphoproliferative and cause cell transformation
Discuss the clinical features we observe in HSV
With the primary infection of HSV, it is accompanied by systemic symptoms such as fever and malaise. With reactivation, we get prodromal symptoms like pain, numbness, itching and a tingling sensation.
Acute infection is where we get the direct destruction of tissues or induction of immunopathologic response.
What is worse with HSV, primary or secondary infection
Primary because you don’t have any immunity yet.
The patient with primary will have many lesions orally called gingivostomatitis all around the mouth, but on recurrent HSV-1, they just get a cold sore.
HSV-2 is associated with:
Genital bumps
What anti-herpes treatment do we have?
Herpes Thymidine Kinases like acyclovir and ganciclovir. The viral Thymidine kinase activates this DNA chain terminator and incorporates it into the viral DNA, causing a termination of replication
Acyclovir vs. Ganciclovir
Acyclovir - For HSV - Activated by viral TK and terminates as previously discussed
Ganciclovir - For CMV - Viral protein kinase analogue of TK activates it.
What does Foscarnet do?
It is a pyrophosphate analog that binds directly to the RNA pyrophosphate binding sites or to DNA polymerases.
Unlike ganciclovir and acyclovir, it does not need to be activated by anything.
We use it primarily for CMV
Discuss the general structure and physical attributes of fungi
- Eukaryotic
- Cell wall has chitins and glucans
- Fungal membrane contains ergosterol, which is not in humans
- No endotoxins
Three possible structures of fungi
Unicellular Yeast
Filamentous multicellular mold
Dimorphic (either)
How do yeast reproduce?
Budding and binary fission
How is mold organized?
In compartments within hyphae that grow outwards. The compartments have different organelles in them with pores between the compartments
What is the function of Sabouraud’s agar?
For growing fungus. It inhibits bacterial growth with a low pH along with chloramphenicol and cycloheximide
What do azoles do?
Inhibit ergosterol synthesis
What do polyenes do?
Bind ergosterol and make pores in the wall
What do echinocandins do?
Inhibit synthesis of B-glucan and block cell wall
Side effects of fungal medications
Azoles - Can cause visual disturbances but are generally well tolerated
Polyenes - Renal toxicity, HA, chills
Echinocandins - GI side effects and flushing
What can our endothelial cells use to detect fungus?
Dectin-1 is a pattern recognition molecule for B-glucan
Defensins
What do we mean by superficial mycoses?
These guys colonize the keratinized outer layer of skin, hair, and nails, and cause a scant immune response. They are typically nondestructive and are just a cosmetic concern
Discuss Pityriasis Versicolor, a superficial mycosis, and how we can see it
Pityriasis versicolor - caused by the Malassezia furfur yeast and causes hypo or hyperpigmented macules on the chest, neck, and back.
We diagnose this with direct visualization of short infrequently branched pseudohyphae in either 10% KOH or a PAS stain
Treating pityriasis versicolor
Topical therapy is needed as it rarely self cures. Azoles work just fine.
Discuss in general cutaneous mycoses and what tends to cause them
Most are caused by dermatophytic fungi (dermatophytes) that break down keratin, invade skin, hair, and nails, and invade the outermost layer of the epidermis (stratum corneum)
The most well known subgroup in this is Tinea, ring worm
Discuss in general subcutaneous mycoses and name the three subtypes
All are rare, and are introduced following trauma. They cause infection into the dermis, subcutaneous tissue, and bone, and rarely spread into distant organs.
Sporotrichosis, Chromoblastomycosis, and eumycotic mycetoma are all examples
