Exam 3 Flashcards
Mast cells
Highly granulated tissue resident cells containing surface expressed FC-epsilon receptor I. Found in mucosa in connective tissue, responsible for maintaining integrity of tissue and altering the immune system of localized trauma.
• cross bound to IgE
Eosinophils
Tissue resident granulocytes that stain heavily with eosin, Principal cause: Id airway damage, chronic asthma 
Basophils
Least numerous of all granulocytes. Secrete Th2 polarizing cytokines, IL-4, IL-13 which stimulate IgE 
Type I hypersensitivity: immediate
• IgE, Th2 cells
• mast cells, eosinophils, basophils, and their mediators (lipid, cytokine, etc)
• wheal and flare response
• atopy: predisposition to IgE mediated sensitization
• Pollen, food, venom, drugs
Type II Hypersensitivity: antibody mediated
• IgM, IgG, against cell surface ECM antigens
• opsonization and phagocytosis
• Complement and FC receptor mediated recruitment and activation of leukocytes (neutrophils, macrophages)
• abnormal cell function (neuro blockade) 
Type III hypersensitivity: Immune complex mediated
• immune complex is circulating antigens
• IgM, IgG
• Complement and FC receptor mediated recruitment an activation of leukocytes
Type IV hypersensitivity: T-cell mediated
• CD4+ T cells (Th1, Th17)
• Cytokine mediated inflammation and macrophage activation
• CD8+ CTLs
• Direct target cell killing, cytokine-mediated inflammation
Immediate hypersensitivity
Allergen + B cell —> presents to Th2 cell —> makes memory cell + plasma cell —> sensitizes mast cell —> allergen re-presented —> granulocyte response
Contents of mast cell granules 
Enzyme: tryptase, chymase, cathepsin G, carboxypeptidase
Toxic mediator: heparin, histamine
Cytokine: TNF-alpha 
Prevention of hypersensitivity I
Desensitization: Serial application of allergens in gradually escalating doses
Anti-IgE antibodies: expensive, not worth 
Examples of type II hypersensitivities
• Goodpasture’s syndrome
• Graves’ disease
• Myasthenia gravis
• Erythroblastosis fetalis
Immune complexes (type III)
• formed between antibody and antigen, get deposited in tissues
• ICs Result from: persistent infection, inhalation, auto immune disease, cryo-globulins
Diseases that result from type III hypersensitivities
Auto immune diseases: SLE, rheumatoid arthritis, multiple sclerosis
Drug allergies: penicillin and sulfonamides, serum sickness
Infectious diseases: post streptococcal, glomerulonephritis, meningitis, hepatitis, mononucleosis
T cell mediated inflammatory response (CD4+, type IV)
• most destructive, requires antigen specific effector T cells to activate macrophages (Th1)
• Antigen presenting cells: macrophages, Langerhans cells
Contact hypersensitivity (Type IV)
• Eczematous skin reaction
• Nickel, rubber, dyes, fragrance, plants
• Haptens: Small sensitizing agents that penetrate skin (help bind self-peptide to MHC class II making it immunogenic)
Dinitrochlorobenzene (DNCB)
Hapten from plants that sensitizes nearly everyone (poison ivy/oak/sumac) 
Granulomatous hypersensitivity
• tuberculin — TB test is an example of type IV hypersensitivity
• also leprosy, Crohn’s, schistosomiasis, and Sarcoidosis 
• persistence of antigen within macrophages due to killing mechanisms being blocked or particles that the cells cannot destroy
Multi nucleated giant cells
Macrophage —> epithelium’s cells
• cells that lose many functions such as mitochondria and ER, but produce a lot of TNF-alpha to continue hypersensitivity response (chronic Th1 activation)
Contact dermatitis cytokine responses
— IL-2
— IL-8
— IFN- gamma
— GM- CSF
Haptens
• Highly soluble, highly reactive, bind covalently and non-specifically to skin proteins which activates Th1 cells, CD4+ T cells in the skin (type IV)
• your hands can spread these in linear patterns and to your eyes (wherever you touch)
Pentadecacatehol
A common hapten, found in poisonous plants
Treating contact dermatitis
Corticosteroids: block the transcription of pro-inflammatory genes, and up regulate the production of inhibitors of pro-inflammatory transcription factors (Immunosuppressive)
Antihistamines: help with itching, block histamine receptors on mast cells to reduce histamine release, does not improve rash
Poison ivy
• appearance of rash two days after exposure (must be 2nd exposure at least)
• Red, raised blistering lesions of contact dermatitis
• Infiltration of blood cells into the tissue at the site of contact with the Hapten
• Death of local tissue cells, destruction of ECM = blisters 
Contact dermatitis and Th1 T cells
1.) antigen is injected into subcutaneous tissue and processed by local antigen presenting cells
2.) A Th1 effector cell recognizes antigen and releases cytokines that act on vascular endothelium 
3.) recruitment of phagocytes and plasma to the site of antigen injection causes a visible lesion
Outcomes of CD4 T cells engaging with Hapten in the periphery
1.) IFN-gamma
2.) TNF-alpha and/or LT
3.) chemokines
4.) IL-3 and/or GM-CSF
IFN-gamma
Induces expression of vascular adhesion molecules. Activate macrophages, increasing release of inflammatory mediators
TNF-alpha and/or LT
Local tissue destruction. Increased expression of adhesion molecules on local blood vessels
Chemokines
Macrophage recruitment to site of antigen
IL-3 and/or GM-CSF
Monocyte production by bone marrow stem cells
Direct Coomb’s test (positive)
1.) blood sample from a patient with immune mediated hemolytic anemia: antibodies on RBC surface
2.) The patient RBCs are washed and incubated with anti-human antibodies (Coombs reagent)
3.) RBCs agglutinate, Anti-human antibodies form links between RBCs by binding to the human antibodies
• Looking for the antibody on the cell in the donor
Indirect coombs test (positive)
1.) recipients serum is obtained, containing antibodies
2.) Donors blood sample is added to the tube with serum
3.) Recipients antibodies that target the donors RBCs form antibody antigen complexes
4.) Anti-human antibodies are added to the solution (Coombs reagent)
5.) Agglutination of RBCs occurs, because human antibodies are attached to red blood cells
• Looking for antibody in recipient for what donor has

Gastrulation layers
Ectoderm: epidermis, CNS
Mesoderm: musculoskeletal, cardiovascular, urogenital
Endoderm: lining of G.I. tract and respiratory tract
Gastrulation layer descriptors
Endoderm: Cuboidal epithelium
Ectoderm: columnar epithelium
Mesoderm: mesenchyme (multipotent)
Notochord and neural tube
• overlaid by ectoderm
• Signals the overlying ectoderm to thicken and old, folds come together to form neural tube
• Incomplete closure of neural tube leads to anencephaly
Neural crest
• arise from ectoderm
• Multipotent cells at the border of the neural plate
• Contribute to PNS, craniofacial cartilage, melanocytes, endocrine cells, glia
Mesoderm
• mesenchyme, Embryologic connective tissue
• divides into:
—Paraxial mesoderm (Somites)
—intermediate mesoderm (urogenital)
— Lateral plate mesoderm (parietal and visceral)
Somites
• mesenchymal tissue derived from Paraxial mesoderm
• Cranial most somites are called somitomeres and contribute to the head
• Sclerotome, myotome, dermatome
Epaxial
Skeleton muscle innervated by dorsal rami of the spinal nerve
— Intrinsic back muscles
Hypaxial
Skeletal muscle innervated by ventral rami of spinal nerve
— Abdomen, superficial back
Lateral plate mesoderm
1.) parietal (somatic) mesoderm : adheres overlying ectoderm, body wall including limb buds
2.) Visceral (splanchnic) mesoderm : Adheres to underlying endoderm, muscular wall of the gut, circulatory system
 apical ectodermal ridge
• proliferation of mesenchymal cells in the progress zone
• Key for limb development, without limbs do not form
Progress zone
• site of proliferation of Limb bud
• Proximal to distal growth pattern
Zone of polarizing activity (ZPA)
• Key for Anteroposterior patterning (medial lateral in the adult)
Limb buds are influenced by what?
• HOX genes
• Aer signals for proximodistal development (stylopod, zeugopod, autopod)
• Dorsal and ventral ectoderm specifying the dorsoventral patterning
• ZPA causes the expression of SHH genes to control anteroposterior patterning
Amelia
Absent Limb
Meromelia
Partial absence of limb
Hemimelia
Absence of the fibula
Phocomelia
Reduced/shortened limb
Talipes equinovarus
Club foot, sole is turned mediately, foot is inverted
Digit formation
- AER is responsible for proximal distal patterning
2. ZPA is responsible for anteroposterior patterning (Shh, asymmetry in the 5 fingers— thumb has none, pinky has a lot)
Polydactyly
Born with extra digits, can be soft tissue only, soft tissue and bone, skin and soft tissue and multiple bones
(most commonly on the pinky side)
Syndactyly
Failure of intra-digit apoptosis resulting in fused digits after birth
(Simple, complex, complicated)
Limb rotation
• explains the dermatome pattern on adults
• Upper limbs are externally/laterally rotated— dorsal elbows
• Lower limbs are internally/medially rotated— ventral knees
Bone formation
1.) Endochondral ossification (most common) — Cartilaginous precursor model becomes bone
2.) Intramembranous ossification — Bone forms within membrane sheaths (skull, clavicle)
Endochondral ossification
1.) cartilaginous model: chondrocytes create new cartilage
2.) Cartilaginous model is replaced by bone: osteoblasts create new bone
3.)  Bone growth occurs at the epiphysis of primary and secondary ossification centers
Diaphysis
Bone shaft
Epiphysis
Bone growth plate
Fibrous joints
- Sutures: connect cranial bones
- Gomphoses: Connect teeth to alveolus
- Syndesmosis: slightly mobile such as radius and ulna connection
Cartilaginous joints
— Hyaline or fibrocartilage
- Synchondrosis: Hyaline cartilage, epiphyses
- Symphyses: Either Hyaline or fibrocartilage: pubic symphysis
Synovial joints
Mobile joints characterized by a joint capsule filled with synovial fluid
— Joint capsule is fibrous connective tissue
— Articular cartilage is Hyaline
Types of synovial joints
Planar: acromioclavicular
Hinge: elbow
Pivot: atlantoaxial
Condyloid: metacarpophalangeal
Saddle: thumb CMC1
Ball and socket: hip, shoulder
Congenital infantile hyperpituitarism
Gigantism: excessive growth hormone, increased height before Epiphyseal seal
Acromegaly: excessive growth hormone after epiphyseal fusion, affects shape and morphology of phones and soft tissue
Skeletal system
Axial skeleton: Skull, Vertebral column, ribs, sternum
Appendicular skeleton: pectoral and pelvic girdles, limbs
Intravertebral disc development
• Notochord becomes the nucleus pulposus
• sclerotome becomes annulus fibrosus
Spina bifida
— Failure of the halves of the embryonic cartilaginous neural arch to fuse
1.) Occulta: occurs at the L5 or S1 vertebrae. Minor form can produce no symptoms or minor symptoms (tuft of hair or small dimple at lower back)
2.) Cystica: protrusion of spinal cord and or meninges — Including meningocele (CSF, meninges), and myelomeningocele (spinal nerves/cord/roots)
Klippel-Feil Syndrome (Brevicollis)
• congenital effusion of cervical vertebral bodies
• Restricted neck movement
• Smaller cervical nerve roots
Congenital scoliosis
Results from lack of an ossification center, incorrect segment, or vertebral fusion 
 Development of the ribs
• come from mesenchymal costal processes of the thoracic vertebrae
• Begin as cartilaginous and then ossify
• Site of union of the costal process with the vertebra is replaced by costovertebral synovial joint
Development of the sternum
• Sternal bars: vertical mesenchymal bands
• Convocation occurs as these bars move medially and then fuse
• Cartilaginous models of the manubrium, sternebrae, and xiphoid process
Cervical ribs
Usually rudimentary, development of the costal processes of the cervical vertebrae, usually attached to the seventh cervical vertebrae as tiny nubs
Thoracic outlet syndrome
Compression due to the narrowing of the superior (cranial) opening of the thoracic cage from cervical ribs
Lumbar ribs
Development of the costal processes of the lumbar vertebrae, usually attached to the first lumbar vertebrae, benign
Sternal foramen
Varies in size, results from incomplete fusion of the cartilaginous sternal bars during development (looks like a gunshot wound) 
Pectus excavatum
Concave depression in the lower sternum, pushes on lungs and heart
Muscle development
1.) skeletal as you grow
2.) Smooth, from splanchnic mesenchyme surrounding the primordial gut
3.) cardiac, from lateral splanchnic Mesoderm, forms the conduction system of the heart: Purkinje fibers
Poland syndrome
Absence of pectoralis major and minor, ipsilateral breast hypoplasia, absence of 2-4 ribs, occasionally absent mammary gland
Torticollis
— Wryneck
— Shortened fibers of sternal cleidomastoid muscle
— Lateral bending of the head to the affected side and slight turning away from the side of the shortened muscle
Acne vulgaris
Inflammatory disease of the pilosebaceous unit
Comedones
Baseline of acne, small solid bumps
Acne vulgaris epidemiology
• Peak ages of 14 to 19, 80% of adolescents in the USA
• Androgens, diet, genetics, stress, insulin resistance, mechanical trauma, tobacco
Microbiology of acne
Cutibacterium acnes: propionobacterium
• Stimulation of sebocytes and monocytes to secrete IL-1-beta
• Direct effect on T cells, modulation of keratinocyte expression of integrins and filaggrin 
Pathophysiology of acne vulgaris
— chronic inflammation of the pilosebaceous unit
1.) Increased sebum production by sebaceous glands
2.) abnormal shedding of follicular epithelium/hyperkeratinization
3.) Colonization of follicle
4.) Inflammatory reaction
Grading level of acne vulgaris
I. Superficial non-inflammatory
II. Superficial inflammatory
III. Deep inflammatory
IV. Severe nodulocystic (scar)
Acne fulminans 
Rare and severe with abrupt development of large inflammatory nodules and friable plaques (erosion, ulcers, hemorrhagic crusts)
Treated: Oral glucocorticoids, oral isoretinoin
Acne conglobata
Severe form of nodular acne vulgaris (Drainage, sinus tracts, severe scarring)
Treated: systemic or intralesional glucocorticoids, surgery, TNF alpha inhibitors
Azelaic acid
Expensive, Tyrosinase inhibitor
Dapsone (aczone)
Antibiotic but works by inhibiting inflammation, expensive prescription, no induced resistance known
Benzoyl peroxide
Antibacterial/not antibiotic, over the counter as a single agent, cheap
Salicylic acid
Cheap over the counter, present in cleaning products
Topical antibiotic treatment
• benzyl peroxide addition
• clindamycin
• Erythromycin
Oral antibiotic treatment
• doxycycline
• Minocycline
• Addition of benzyl peroxide to reduce your distance
• Used trimethoprim/sulfonamide if rate of allergic reaction is higher
Topical retinoid
• reduce number of comedones
• Anti-inflammatory properties
• Adapalene (Differin)
• Tazarotene (Tazorac)
• Tretinoin (Retin-A)
Acne pomade 
Closer to hair distribution, forehead and temple regions
Acne Mechanica
Occurs under headbands, helmets, shoulder padding, under chin, CPAP masks etc.
Acne rosacea
Papules and pustules on broad base of erythema and telangiectasia, Central third of the face
Triggers include: son, stress, hot weather, wind, exercise, alcohol, etc.
Erythematotelangiectatic rosacea
Flushing and persistent central face erythema with or without telangiectasia 
Papulopustular rosacea
Persistent central face erythema, transient central facial papules and or pustules
Phymatous rosacea
Second skin, irregular surface nodularity and enlargement. Typically on the nose, chicken, forehead, cheeks, ears
Ocular rosacea
Eye has foreign body sensation, burning stinging and itching, photo sensitivity in third vision, telangiectasia of sclera and other eye parts, Peri orbital edema (50% of Rosacea cases)
Granulomatous rosacea
• uniform red/brown or yellow/brown papules on face
•  Typically needs oral management
Pediatric rosacea
• rare
• Tetracyclines contraindicated
Treatment of rosacea
• avoidance of triggers
• Appropriate skin care to maintain integrity of stratum corneum
• Photo protection
• Medication
Skin look-alikes
1.) acne vulgaris and contact dermatitis
2.) Photodermatitis and seborrheic dermatitis and systemic lupus erythematosus
Pemphigus vulgaris
Intradermal split from loss of cohesion between keratinocytes secondary to an antibody mediated attack
• Stevens Johnson syndrome/toxic epidermal necrolysis (SJS/TEN)
• SSSS (A and B exotoxins)
• elderly patients, painful flaccid blisters that easily rupture. Oral/ocular mucosal membranes often involved
Pemphigus vulgaris pathology
• blister forms within the epidermis above the basal layer, due to autoantibodies directed at Desmogleins 3 and 1 within the desmosome
• C3 and IgG
Contributing factors to pemphigus vulgaris
• genetics is the most important
• Also included are Colon environment, drug exposure, diet
Treatment of the pemphigus vulgaris
1.) topical or systemic corticosteroids
2.) Oral immunosuppressive agent: dapsone, tetracyclines, methotrexate
3.) IV immunoglobin or anti-CD 20 monoclonal antibodies (rituximab)
Bullous pemphigoid
• Itchy, multiple and tense blisters
• elderly, rare in mucous membranes
• Can last days to weeks
• Dermal epidermal junction (Hemodesmosomes) due to autoantibodies targeting bullous pemphigoid antigen
• linear deposit of C3 and IgG at basement membrane
bullous pemphigoid and Comorbidities
1.) neurological disorders: dementia, MS, Parkinson’s
2.) Malignancies
3.) genetic factors: HLA alleles/ Auto immune triggers
Bullous Pemphigoid treatment and prognosis
Treatment: topical steroids first, oral glucocorticosteroids. Mycophenolaye, methotrexate, dapsone. Rituximab or IV immunoglobins if refractory to treatment
prognosis: can resolve spontaneously, most often chronic and relapsing 
Dermatitis herpetiformis
• Chronic autoimmune disorder which targets transglutaminase in the skin and gut
•  onset 30 to 40 year old
• Associated with celiac
• Presentation: tiny, itchy vesicles that are usually excoriated, leaving small erosion. Extensor extremities, elbows, knees, scalp

Histopathology of dermatitis herpetiformis
Blister forms at the dermal epidermal Junction with neutrophils and eosinophils at the tip of the dermal papillae. IgA seen
Pathogenesis: genetic— HLA DQ2, HLA DQ8. Or gluten sensitivity 
Treatment of dermatitis herpetiformis
• Gluten elimination
• Dapsone
• Corticosteroids, topical
• Watch for comorbidities (ex. Hypothyroidism)
Epidermolysis bullosa (Non-inflammatory)
Inherited disorder: heterogenous, autosomal dominant, rare
• Structural protein abnormalities within intraepidermal adhesion and dermal epidermal anchoring complex
• fragile skin that blisters with trauma (babies butt/where they are picked up)
Diagnosis of Epidermolysis bullosa 
1.) biopsy, determine layer of skin cleavage
2.) Determine phenotype: distribution, severity, presence of non-skin involvement
3.) Subtypes: Epidermolysis BS, Junctional EB, Dystrophic EB, Kindler EB
Porphyria cutanea tarda
Presentation: photosensitive, non-inflammatory bullae, typically dorsum of hands, scarring, milia and dyspigmentation
Types: most frequently elevated iron levels which inhibit porphyrin metabolism, sometimes genetic
Diagnosis: blood and urine shows an increase in porphryins, urine will fluoresce in a coral-red color under Wood’s lamp
Porphyria cutanea tarda treatments
1.) Treat/avoid the triggers, either from medication, liver disease, excessive iron, Sun damage
2.) phlebotomy, iron depletion reduces formation of the UROD inhibitor and body clears porphyrins
3.) Low-dose hydroxychilorquin
Friction blisters
• From pressure, attention, friction
• Most likely to occur where there is thick stratum corneum
• Takes place within the epidermis, intradermal split in the stratum Spinosum

Main European tickborne illnesses
• babesiosis
• borreliosis
• Crimean Congo hemorrhagic fever
• rickettsiosis
• tick borne encephalitis (viral)
• tick borne relapsing fever (bacterial)
Most common MN tick
Ixodes scapularis
Tickborne illnesses in Minnesota
1.) Lyme disease (b. Burgdorferi, borrelia)
2.) anaplasmosis HGA (a phagocytophilum)
3.) babesiosis (babesia microti) 
Ixodes scapularis
• Black legged tick
• Deer tick
— Eggs not infected, larvae have a bloodmeal and acquire virus/bacteria
— Nymphs and (female) adults transmit disease, typically in late spring and summer
Main pathogen reservoir host
White footed mouse. Both the larval stage and nymphal stage
— adult ticks like to feed on deer (not the Reservoir- last meal)
Measures that protects against tick bites
• DEET Repellent on skin
• Permethrin on clothing
• Light colored clothing (to see)
• Socks outside of pants
• Prompt inspection of skin removal of ticks 
Borrelia Burgdorferi
• cause of Lyme disease transmitted by Ixodes scapularis and Ixodes pacificus
• Fastidious, microaerophilic, Spirochete
• grows at 32 degrees on BSK medium • USA sees b. Burgdorferi sensu stricto and b. Mayonii
What B.Burgdorferi looks like
• 7 to 11 flagella, underneath outer membrane
• Surface proteins or host dependent (OspA in ticks and OspC in humans)
• Remain in midgut of insect until blood meal, then migrate to salivary glands. Can disseminate widely in mammals
Anaplasma phagocytophilum
• causes human granulocytic anaplasmosis (HGA)
• Rickettsia like (requires living cell for growth, extremely small, gram-negative, pleomorphic and shape)
• Ehrlichia is like A. phagocyto. 
Features of Anaplasma phagocytophilum
• replicate in medial epithelial cells
• Salivary gland epithelial is what is transmitted to initiate mammalian infection
• colonizes neutrophils, hijacks endocytic pathway to make vacuole in which to replicate (Morulae)
Rickettsia rickettsii
• responsible for Rocky Mountain spotted fever
• Rickettsia bacterium
• ticks: dermacentor spp., rhipicephalus sanguineus (dog/wood ticks) 
Unique feature of R. Rickettsii
Transovarian passage: infected adult female transmits infection to egg to pass infection from one generation to another
How does rickettsia spread/replicate?
• bloodstream, vascular epithelial cells
• Replicate in cytosol of the cell, not a vacuole (no Morula)
Babesiosis
• develops in red blood cells
• Has X appearing development stage
• Symptoms similar to malaria
• Eukaryotic pathogen, Unicellular protozoan parasite 
Tickborne encephalitis virus
• Transmitted by European ixodes species (EU, Asia, former Soviet Union)
• RNA virus (vax available)
• all common symptoms plus brain/spinal cord swelling, confusion, sensory disturbances
• Hospitalization in supportive care, anti-inflammatory drugs, intubation
Powassan (POW) Flaviviridae virus
• similar to tick born encephalitis
• spherical, enveloped, (+) ssRNA non-segmented, arthropod-borne
• Transmitted by the bite of arthropods (Ticks and mosquitoes)
• Causes Zika, west Nile, dengue, yellow fever
Lyme risk factors
• geography
• Exposure and behavior
• Local Ixodes tick epidemiology
• tick attachment and transmission, 36hrs 
spirochete Pathogenesis
(Borrelia)
— Immune response and evasion
— regulation of surface proteins (OspA—>OspC) 
— Borrelia does not produce proteases or toxins, it minimizes surface protein antigens, allowing immune evasion and dissemination
— Manifestation includes derm, cardiac, Neuro, musculoskeletal system
Early stage of Lyme disease
• fever, chills, HA, fatigue, muscle and joint aches, lymphadenopathy
• Erythema migrans rash (70-80%) That can reach up to 12 inches and me feel warm. Can be bulls eye 
Early disseminated disease stage of Lyme disease
• multiple erythema migrans rashes
• Carditis (1-5%) Including conduction abnormalities and third degree AV block
• Neurologic (10-15%)  including Bell’s palsy, meningitis, peripheral neuropathy, radiculitis
Late disease of Lyme disease
• months to years after infection
• Arthritis, commonly knees, usually presents as a single swollen large joint
• Relapses, relatively less pain and more effusion
• Neurologic (rare) including encephalopathy, and peripheral neuropathy
Lyme diagnosis
• erythema migrans rash and exposure history
• Serology (Helpful in early disseminated and late disease)
• PCR (Useful for arthritis and synovial joint fluid testing)
Lab testing for Lyme disease
1.) serology including ELISA test, And western blot looking for IgM (2 bands) and IgG (5 bands)
2.) specific ELISA: Borrelia—> VIsE C6 EIA
3.) PCR: useful for joint involvement
Lyme disease treatment
1.) doxycycline: 10 to 21 days is the treatment of choice
2.) Amoxicillin: in children less than eight years old and pregnant women
3.)  Ceftriaxone (IV): 14-28 days, Indicated for CNS infection, recalcitrant arthritis
Tick bite prophylaxis
Lyme disease post exposure treatment:
1.) Adult: doxycycline 200 mg POx1
2.) Children: 4 mg/kg x1 (if >8)
Criteria: adult or nymphal deer tick, Attachment for more than 36 hours, geographical relevance
Post treatment Lyme disease syndrome (PTLDS)
Criteria:
• Documented lyme diagnosis
• post treatment resolution
• Onset of fatigue, widespread musculoskeletal pain, complaints of cognitive difficulties six months post diagnosis
• Great impact on life
Inappropriate therapy for Lyme disease
• Beyond 4 week treatment is not beneficial
• IV antibiotic associated complications including C.diff, candida, bacterial endocarditis
Anaplasmosis
• gram-negative rod, and a plasma phagocytophilum
• host: human, deer, white footed mouse
• Vector: Ixodes scapularis
• Shorter attachment and transmission time than Lyme disease
Anaplasmosis diagnosis
• fever, leukopenia, anemia, thrombocytopenia, elevated ALT, AST
Labs: Peripheral smear, whole blood PCR, fourfold change in IgG titer at 2 -4 weeks
Babesiosis
• babesia microti
• Intra-erythrocytic parasite that incubates for 1-9 weeks
• symptoms: fever, fatigue, HA, myalgia, hemolytic anemia
Diagnosis: blood smear (tetrads, x-looking), PCR, serology
Babesia treatment
— Atovaquone + azithromycin
— clindamycin + quinine
Rocky mountain spotted fever symptoms
• rash, fever, HA, nausea, vomiting, abdominal pain (mimics appendicitis), muscle pain, lack of her appetite, conjunctival injection (red eyes) 
• 90% develop a rash: small, blanching, pink macules on the ankles, wrists, forearms that evolve to maculopapules
Doxycycline is the treatment of choice for:
• anaplasmosis
• ehrlichiosis
• RMSF
• any rickettsia infection
• B. Burgdorferi
• miyamotoi
Other tickborne infections of significance
• Colorado tick fever virus
• Powassan virus (Encephalitis)
• Tularemia
• heartland and Bourbon virus
• Tick borne relapsing fever (Borrelia hermsii, Borrelia turicatae)
Urticaria
• Dermis, Wheals or hives
• lesions come and go and appear within minutes to hours
• Localized capillary vasodilation (histamine mediated)
• Can be acute or chronic
• Usually caused by URI, inducible/auto immune, idiopathic
Angioedema
• deeper layers of dermis, mucous membranes
• Histamine mediated (insects, food, drugs)
• Bradykinin mediated (Hereditary, acquired, angiotensin converting enzyme)
• Treat with anti-histamine, H1 blocker
• presents commonly in mucosal membranes and loose skin areas
Angioedema history
—Details of travel, recent infection, occupational exposure, meds, ingestion of foods, exposure to physical stimuli 
— Family history, comprehensive physical exam, including irritation of G.I. tract
Hypersensitivity causes of angioedema
• Type I, IgE
• auto-immune (complement)
• infectious (parasitic, direct mast cell mediated)
Hypersensitivity causes of angioedema
• physical Urticarias (pressure, warmth)
• Direct mast cell degranulation
• Foods containing high levels of histamine
• bradykinin mediated (ONLY ANGIOEDEMA, no rash)
Type I IgE mediated
• Foods
• Latex
• Stinging insects
• Medication: penicillin and cephalosporins
• Areoallergens
Immune but non-IgE mediated
Auto immune:
• Hashimoto’s immune thyroditis
• SLE, vasculitis
Infection:
• Viral, parasitic, fungal, bacterial
Cholinergic Urticaria
Small urticarial papules on red skin, occurring on the neck within 30 minutes of vigorous exercise
Cold urticaria
Appearance of edema from the dermal layer after placing an ice cube on the skin
Dermatographia
Excoriated, urticaria appearing after stroking the skin with a wooden stick. The patient experiences general itchiness 
IGE mediated drug induced urticarias
• beta lactams
• Quinolones
• Iodinated contrast media
• aspirin and NSAIDs
Non-IGE mediated drug induced urticaria
• aspirin and NSAIDs: leukotriene mediated
• Ace inhibitors: bradykinin mediated
• Morphine/opioids: direct mast cell degranulation
Things that cause erythema multiforme
• infections (90%): HSV1, HSV2, mycoplasma pneumonia, EBV, CMV, candidiasis
• Medication: antibiotics, antiepileptics, barbiturates, NSAIDs, statins, sulfonamides, vaccines
Therapy for erythema multiforme
Prevention: control HSV with antivirals, manage chronic illness
Glucocorticoids: prednisone for severe illness
Supportive: fluids, topical steroids, antihistamines for symptom management
Appearance of erythema multiforme
• Central zone is damaged skin, dusky, Bullous, crusted
• Individual lesions are fixed for at least seven days
• All lesions appear in the first 72 hours
• No edema
Stevens Johnson syndrome
• Photophobia, conjunctiva inflamed, skin is dusky, red macular, sensitive, non-blanching, NIKOLSKYS SIGN
• drug exposure typically causes SJS
• Skin detachment of less than 10% of the body surface
Toxic epidermal necrolysis
• similar to SJS, skin detachment of over 30% of body surface
• Drug exposure is the leading cause
• Mortality rate is 25 to 50%
Panniculitis
• rash appears in the SAME PLACE they’ve had previously when taking a drug (Fixed drug eruption)
• subcutaneous tissue inflammation
• Iris and Mattis or violaceous nodule in the SQ fat
• can be purpuric
• Skin biopsy will show hypertrophied septae
Erythema nodosum: Most common panniculitis
• erythematous tender nodules
• septal panniculitis
• Anterior shins
• Does not ulcerate
• Treatment includes rest, ice, pain control
Erythema Induratum: Panniculitis
• tender red nodules
• Lobular panniculitis and vasculitis
• Middle aged, female
• posterior legs
• Chronic, recurrent subcutaneous nodules and alteration can be common
• Associated with TB
Auspitz sign
Pinpoint bleeding when plaques are torn/peeled
Koebner phenomenon
Occurrence of plaques at injury sites
Wickhams striae
Fine, white, Lacey appearance
Psoriasis
• thick, raised, plaques with silver scaling, well demarcated
• Hereditary, peaks between 30-40 and 50-70
• caused by: increased number of epidermal stem cells, shortened cell cycle time for keratinocytes, decreased turnover time of the epidermis
Histopathology of psoriasis
• hyperkeratosis with parakeratosis
• Increased stratum Spinosum, decreased stratum granulosum
• elongation of rete ridges (leads to auspitz sign)
• Neutrophils in the epidermis
Triggers of psoriasis
Obesity, drugs, alcohol, infectious, smoking, vitamin D deficiency, environmental, stress
Chronic plaque psoriasis
• Most common, symmetrical plaques, on the scalp, elbows, knees, gluteal cleft
•
Guttate psoriasis
More common in children and more common with infections as the trigger.
— eruptivr truncal dermatosis, set an onset of teardrop shaped skilled spots of the trunk and proximal extremities
— Greater tendency for spontaneous resolution
Pustular psoriasis
More serious and can be associated with systemic symptoms (life-threatening)
— Generalized or localized, maybe termed pustular psoriasis of Barber
Erythrodermic psoriasis
Like a Burn, more widespread skin involvement, risk of secondary infections due to denudes skin, rare
Inverse psoriasis
Intertriginous areas, axillary, inguinal, perineal, genital, under breasts
— May look like a yeast infection (Steroids will make psoriasis better and yeast infections worse)
Nail Psoriasis
Can be singular presentation but expect progression two other forms, closer association with psoriatic arthritis
psoriatic arthritis
• inflammatory, seronegative arthritis with a variable course
• Asymmetric and primarily involves the fingers and toes. Inflammation and insertion of tendon to bone, tenosynovitis and dactylitis (sausage fingers)
• 1/3 of pts w psoriasis
Lichen simplex chronicus (lichen planus) 
WICKHAMS STRIAE
• Will not be present where patient cannot reach (Polygonal, flat topped plaques, Oral, vulvar, wrists, shins, scalp)
• six P’s: planer, purple, polygonal, Pruritic, papules, plaques
• Association with hepatitis C
Lichen planus cutaneous variance
1.) hypertrophic
2.) Annular
3.) Bullous
4.) Scalp: lichen planopilaris
5.) Actinic LP
6.) LP pigmentosus
7.) Inverse LP
8.) Atrophic LP
Systemic lupus erythematosis
• ACLE, SCLE, CCLE
• Association with genetics, hormones, immunology, environmental
• Poorly cleared apoptotic debris, self antibodies, activated TLRs
Histology of lupus
1.) Hyperkeratosis
2.) follicular plugging
3.) Perivascular and Periadnexal infiltrate
4.) Vacuolar interface change
5.) Second basement membrane
6.) mucin 
Vascular SLE
• Raynaud phenomena
• vasculitis
• Thromboembolic
• Palpable purpura
• Digital officers
Ophthalmologic SLE
• Sjogren’s syndrome
• Retinal vasculopathy
• thickened, scaly rash on eyelids
• Neurological disorders
Hematologic SLE
1.) anemia
2.) Leukopenia
3.) Thrombocytopenia
4.) Lymphadenopathy and splenomegaly 
Antiphospholipid antibody syndrome
• like SLE
• Hypercoagulable state, requires lifelong anticoagulation
• Recurrent spontaneous abortion
• Thrombocytopenia
Cellular layers involved
•Urticaria: dermis
•Angioedema: deep dermis, mucous membranes
•Erythema multiforme: epidermis and dermis
•SJS/TEN: epidermis and dermis
•fixed drug eruption: epidermis
•panniculitis: deep subQ, fatty layer
Necrotizing fasciitis
Infection leading to the necrosis of subcutaneous tissue. Severe pain is common. Infection should be treated very seriously and aggressively through surgery and IV antibiotics and fluids
Acute infectious arthritis
Rapid progression of joint infection. Usually bacterial in origin
Osteomyelitis
Inflammation and destruction of bone caused by bacteria, mycobacteria, or fungi. Causes localized bone pain and tenderness. 80% of infections result from continuous spread or from open wounds
Myositis
Infection of the muscle that leads to muscle inflammation. Can be caused by many different microorganisms including viruses, bacteria, and helminths.
Three ways for bacteria to initiate infection
1.) Breach the skin
2.) Systemic disease
3.) Toxin mediated damage
