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| Disease | Features |
|---|---|
| Malaria: plasmodium falciparum (most aggressive), ovale, vivax, malariae | protozoa feed on hemoglobin in RBCs; infects 25% of developing world |
| Plasmodium falciparum | can be "malignant" malaria (other sp. generally benign); PfEMP1 adherent molecule on surface of infected RBCs clumps them; adhere to small vessels; systemic effects d/t disruption of microcirculation (Sickle cell, G6PDH def = resistance) |
| Malaria clinical symptoms | fever, fatigue, chills, night sweats, anemia, thrombocytopenia, splenomegaly, renal failure, acute respiratory distress syndrome; most deaths in children |
| Babesiosis - tick parasite infxn | DDx is malaria; only minority of pts suffer severe illness; lethal in immunocompromised/splenectomized pts; dx is difficult b/c ticks can be associated with Lyme disesae or erlichiosis |
| Leishmaniasis - localized cutaneous | d/t sandfly bite and L. mexicana or L. donovani infxn; endemic from TX southward; inflammatory papule/ulcer at site of bite (Bagdad Boil); regional lymphadenopathy; usu spontaneously resolves but parasite remains |
| Leishmaniasis - visceral | aka: Kala-Azar; India/Brazil; L. donovani; inflammatory papule, fever, splenomegaly, anemia, leukopenia, lymphadenopathy; intrauterine transm/congenital visceral; may lead to cutaneous; disseminated = multiorgan dysfxn and immune def; fatal in HIV |
| Chaga's Disease | intracellular parasite infects WBCs first, then others after dissemination via blood/lymph; myocardium, neuronal plexuses; dysmotility/dilation of esophagus/colon/ureters/ |
| Chaga's Disease phases | 1. Acute: inflam papule at site, fever, lymphadenopathy, hepatosplenomagaly; 2. Latent: yrs depending on immune system; 3. Symptomatic Phase: few pts, heart, bowel, CNS...aggressive in AIDS |
| Chaga's Disease on the Boards! | clinical manifestations include a combo of myocarditis (cardiomegaly and CHF), dilation of esophagus (achalasia or megaesophagus), dilation of colon (megacolon), dilation of ureter (megaureter) |
| Strongyloidiasis | autoinfxn can lead to disseminated hyperinfxn (immune compromised pts esp w/high dose CCsteroids, pneumonitis/SOB, may be fatal; inc incidence of bacterial sepsis d/t bowl wall damage from invasive larvae |
| Strongyloidiasis on the Boards! | the only helminth able to complete entire life cycle in human host which can lead to autoinfection |
| Cestoidiasis (tapeworms): Tinea solium | Cystericosis (somatic Taeniasis); ingestion of EGGS not larvae = intermed host; eggs form larvae (cysticercus); infect CNS, eyes, skeletal muscle and subcut tissue; Neurocycsticercosis has high mortality (seizure/hydrocephalus/chronic meningoencephalitis) |
| Echinococcus species | larvae disseminate to lungs/liver; form hydatid cysts; enlarge slowly over years; can disseminate to bone, heart, CNS |
| Schistosomiasis | d/t trematodes (flatworms/flukes) in blood, liver/biliary tract, lung, intestine; Initial symptom from skin penetration = Swimmer's Itch; Immunopathologic rxn to disseminated adult worms: Katayama syndrome (fever, lymphadenopathy, hepatosplenomegaly) |
| Chronic schistosomiasis | depends on tissue-tropism of the species; Liver disease (portal hypertension and cirrhosis; UGI bleed/liver failure); Intestinal disease (abdominal pain/diarrhea); Pelvic and urinary disease (dysuria/hematuria) |
| Schistosomiasis on the Boards! | only the blood fluke, S. haemotabium, predisposes to cancer ==> squamous cell carcinoma of bladder |
| Schistosomal Dermatitis | "swimmer's itch" - the schistosomes that are non-pathogenic to humans find man as a terminal host; the cercaria enters the skin and dies, the enzymes elaborated for penetration and waste products are released causing intense inflam and itching after 12hrs |
| Lymphatic Filariasis | adult nematodes in lymphatic channels/nodes cause intense granulomatous inflam rxn that obstructs channel causing lymphedema ==> Elephantiasis or Pachydema |
| Acquired Toxoplasmosis | T. gondii ingested from infected meat (sheep/pig/beef) or sporulated oocysts from cat feces; Infxn can be primary or activated latent; aggressive in immune deficient (necrotizing lesions in CNS/lungs/heart/eyes)...CNS most common |
| Congenital Toxoplasmosis | 1st trimester (during organogenesis) - Transplacental transmission is low, but effects are severe; 2nd Trimester: transmission common but effects are minimal; Toxo Triad: 1.chorioretinitis, 2.hydrocephalus, 3.cerebral calcifications |
| Entamoeba histolotica | bowel mucosa ulcerations, intense inflam 1/20 complicated by intestinal perforation; liver abscess; disseminated amebiasis rare in immunocompetent |
| Entamoeba histolytica: Amoebic colitis | aka: amoebic dysentery w/ mucosal inflam and ulceration |
| Entamoeba histolytica: Amoeboma | aka: amoebic granuloma; tumor-like chronic inflam proliferation in wall of colon |
| Entamoeba histolytica: Amoebic hepatitis | d/t systemic spread of protozoan to liver; can be primary hepatic infxn w/o dysentery prodrome |
| Entamoeba histolytica: Amoebiasis cutis | systemic infxn including skin and lung |
| Giardiasis | fecal-oral; acute and chronic gastritis and/or enterocolitis, but does NOT cause dysentery (ie: not invasive) |
| Thichomonas | d/t trichomonas vaginalis; most acquire asymptomatic infxn and remain as asymptomatic carriers; causes non-invasive infxn in females (vaginitis) or in males (urethritis); rarely causes cystitis in females/prostatitis in males; Strawberry cervix sign |
| Cryptosporidiasis | fecal-oral; diarrhea self-limited in immunocompetent; AIDS/other immunocompromised ==> chronic diarrhea leads to dehydration/malnutrition and systemic dissemination |
| Ascariasis | large intestinal roundworm; chronic malnutrition (worms consume 10% of food ingested); intestinal obstruction d/t heavy worm population; infrequently causes biliary tract obstruction |
| Enterobius vermicularis | pinworm; most common parasitic infx in USA; may be asymptomatic; nocturnal perianal pruritis from females depositing eggs |
| Hookworms | cutaneous larva migrans "ground itch" - inflam localized rash w/streaks d/t larval migration; Pneumonic phase (cough/SOB); Intestinal phase (heavy blood loss/anemia; malabsorption); INC incidence of ANEMIA |
| Cutaneous larva migrans | contact w/nematode larva in soil; 2nd most common parasite in USA; hands/feet/butt/knees; self-limiting 4-8wks; secondary infxn common (S. aureus or S. pyogenes) |
| Clonorchiasis | aka: Asian liver fluke; from uncooked seafood; infects bile passages; marked inc of suppurative cholangitis leading to acute biliary tract obstruction (jaundice, intense pruritis, dark urine, pale feces) |
| Fascioliasis | aka: sheep liver fluke (Mexico southward); veggies/fish w/cysts; marked inc of suppurative cholangitis leading to acute biliary tract obstruction (jaundice, intense pruritis, dark urine, pale feces) |
| Paragonimiasis | Mexico and southward; infected fish/snails; spontaneous pneumothorax, chronic coughing/dyspnea; hemoptysis |
| Case Presentation: Paragominiasis | 39yo Korean male, CC: acute chest pain, Xm: bilateral pneumothoraces, Clinical Course: onset of heoptysis 3wks later d/t infxn of adult flukes; eosinophilia, parasite eggs in sputum; lung Bx: granulomatous inflam |
| Dermatobiasis (maggot infxn) | aka: Human Botfly Myiasis; eggs laid in stomach of mosquito/blood sucking insect that are deposited in human skin w/bite; Larvae hatch and burrow into skin causing a raised area: WARBLE; does NOT become systemic even in immunocompromised; Tx: remove larva |
| Scabies Mites | intense pruritis; linear erythematous lesions (burrows) w/inflam papules; burrowing females avoid hairy areas; preferential sites include wrists, sides of fingers/feet, penis, under breasts |
| Pityriasis/Tinea Versicolor | hypo or hyperpigmented patches on skin d/t Malassezia furfur of normal skin flora; lives in hair follicle and sweat glands; goes away w/age as you get more immunity |
| Cutaneous Mycoses | Trichophyton sp, Microsporum sp, Epidermophyton sp; direct contact from humans/animals; confined to keratinous zone of skin; look for hyphae w/KOH in skin scrapings; examine under Wood's light |
| Cutaneous mycoses: Tinea capitus | aka: ringworm of scalp; often associated w/alopecia; may or may not be w/inflam; a kerion is raised, edematous lesion of scalp manifests granulomatous inflam and secondarily invaded by bacteria |
| Cutaneous mycoses: Tinea barbae | fungal folliculitis |
| Cutaneous mycoses: Tinea corporis | aka: ringworm; only involves glabrous skin (thin skin?); usu annular lesion w/vesicopustular border |
| Cutaneous mycoses: Tinea cruris | aka: Jock Itch; located in groin, freq a/w tinea pedis |
| Cutaneous mycoses: Tinea pedis | aka: athlete's foot; may be dry and hyperkeratotic, vesicles/pustules; intertriginous and macerated w/fissures; secondary bacterial infxn common |
| Cutaneous mycoses: Tinea manus | infxn of hand w/ symptoms similar to tinea pedis |
| Subcutaneous mycoses: Sporotrichosis | aka: Rose Gardner's Disease; plant/tree fungus; inflam papule that ulcerates; low grade lymphangitis; eruption of other inflam papules in lymphatic drainage (chain of lesions); can be misdiagnosed by cellulitis...these are nodules |
| Systemic mycoses: Histoplasmosis capsulatum | endemic to Ohio/Missouri/Mississippi River Valleys; fungal pneumonia; spreads out from hilar areas; prolonged exposure to soil/dust/bird and bat droppings/immunodeficiency; Infects macrophages; granulomatous/scars/calcification inlung and spleen |
| Chronic progressive pulmonary histoplasmosis | aka: chronic fibrocavitary pneumonia; occurs in pts w/chronic lung dx (COPD, CF); rare; causes diffuse fibrosis often w/cavities followed by cor pulmonale |
| Chronic progressive histoplasma mediastinitis | probably d/t lymphatic spread from primary lung infxn; intense fibrosis can lead to compromise of vital mediastinal structures |
| Acute disseminated histoplasmosis | ONLY in immunodeficient pts; simulates bacterial sepsis; may involve skin, mucous membranes, liver, heart valves, GI tract and CNS (histoplasma meningoencephalitis); Hepatosplenomegaly/leukopenia/DIC/adrenal insufficiency |
| Chronic Disseminated Histoplasmosis | very uncommon; usu ONLY occurs in immunocompetent older adults |
| Ocular Histoplasmosis Syndrome | central retinal degeneration and fibrosis leading to vision loss; probably Type IV hypersensitivity rxn rather than active infxn; distrophic calcifications |
| Systemic Mycoses: Coccidiomycosis | SW USA; very large yeast form; fungal spherules w/many endospores; intense granulomatous inflam; primary pneumonia (asymptomatic; fever, chronic cough, SOB, erythema multiforme/nodosum d/t Type IV cell mediated hypersensitivity rxn |
| Coccidiomycosis: Lab Dx | b/c of infectivity level, health care and lab personnel handling specimens are at risk of aerosol exposure...hospital outbreaks occur |
| Coccidiomycosis: clinical course/sequelae | most are self-limited in immunocompetent pts; lung infxns can resolve w/ a small "coin lesion" fibrous scar (coccidioidoma); can remain latent in scar and reactivate yrs later w/immune suppression |
| Coccidiomycosis variants: Chronic Progressive Pulmonary Coccidiodomycosis | primarily occurs in pts w/ chronic lung disease |
| Coccidiomycosis variants: Acute disseminated coccidiodomycosis | can be hematogenously disseminated in pts w/immune deficiency; lymph nodes, bones, skin, subcutaneous tissue, CNS, others |
| Systemic mycoses: Blastomycosis | Ohio River Valley |
| Systemic Mycoses: Cryptococcosis | grows heavily in pigeon feces; most strains have thick polysaccharide capsule; prolonged aerosol exposure to soil/dust w/pigeon droppings; aggressiveness of C. neoformans advances to hematogenous spread in immunocompromised; Dx: india ink halo |
| Opportunistic Mycoses: #1 Candidiasis | C. albicans; pseudohyphae formed from chain of budding yeast cells; most common fungal pathogen; common cause of hospital septicemia |
| Candidiasis risk factors | chronic medical instrumentation (esp IV catheters); IVDA; chronic antibiotic/CCsteroid use; ChemoRx; post-transplant w/chronic immunosuppressive Rx; HIV; IDDM; congenital immunodeficiency (esp cell-med defects); elderly; pregnant |
| Candidiasis: Mucocutaneous | oral thrush; vuvlovaginal thrush; balanitis (penile surfaces); folliculitis; diaper candidiasis; neonatal cutaneous candidiasis; intertrigo (intertriginous areas; skin folds); scattered erythematous lesions w/cottage chees exudate/pseudomembranes |
| Candidiasis: angular cheilitis | aka: commisural cheilitis; angular stomitis, or perleche) |
| Candidisis: onychomycosis | infxn of nails |
| Candidiasis: paronychial infxn | infxn of nail folds |
| Candidiasis: candidal esophagitis | variant of mucocutaneous candidiasis |
| Candidiasis: others | pulmonary candidiasis; candidal cystitis |
| Candidiasis: Candidal Septicemia | aka: disseminated candidiasis: acute or chronic; often a/w septic shock syndrome; skin (secondary cutaneous candidiasis); endocarditis/myocarditis; pyelonephritis; pneumonia; bone (osteomyelitis); peritonitis; septic arthritis; endopthalmitis; meningoence |
| Opportunistic Mycoses: #2 Asperigillosis | septate and acutely branching hyphae at acute <90degree angles; most common is A. fumigatus; granulomatous inflam in immunodeficient pts ONLY; vasculotropic leads to vascular destruction and down-stream necrosis/hemorrhage; |
| Asperigillosis: Hypersensitivity Pneumonitis Group | chronic inflam d/t bronchiectasis and/or pulmonary fibrosis; prominant eosinophil pop w/in inflam |
| Asperigillus: Hypersensitivity Pneumonitis Group - Allergic Bronchopulmonary Asperigillosis (ABPA) | up to 1 in 10 asthmatics; 1 in 8 CF pts; allergic/hypersensitivity rxn to colonization in trachobronchial airways; may or may not be a/w allergic fungal sinusitis; not in lung tissue; wheezing; eosinophilia; elevated IgE |
| Asperigillus: Hypersensitivity Pneumonitis Group - Bronchocentric Granulomatosis | aka: bronchopumonary apserigillosis; very rare; variant of ABPA w/ predominance of granulomatous inflammation |
| Asperigillus: Hypersensitivity Pneumonitis Group - Malt Worker's Lung | aka: Brewer's Lung; very rare; mold (asperigillus clavatus) forms on malt and is inhaled in large concentration |
| Asperigillus: Asperigilloma | aka: fungus ball; mass of hyphae w/in a cavitating lesion of the lung |
| Asperigillus: Sinonasal Asperigillosis | may form a sinus asperigilloma; may become locally invasive causing a fibrosing, granulomatous inflammation |
| Asperigillus: Otitis Externa | aka: otomycosis; growth of asperigillus on cerumen and w/in external auditory canal |
| Asperigillus: keratitis | keratitis from fungus |
| Asperigillus: Acute invasive pulmonary asperigillosis | usu a/w A. fumigatus; only in immunodeficient; simulates bacterial pneumonitis |
| Asperigillus: Chronic Necrotizing Pulmonary Asperigillus | common in pts w/ COPD or other chronic lung disease; vasculotropic fungi cause vascular damage and multiple small pulmonary infarctions surrounded by hemorrhage (aka: halo sign) |
| Asperigillus: Disseminated asperigillus | usu begins in URTI or pneumonia and then disseminates; ONLY in severely immunocompromised |
| Asperigillus: Cutaneous | from an ulcerated lesion; only in immunodeficient |
| Asperigillus: Lab Dx and Radiology | sputum is negative: Galactomannan antigen ELISA assay; Xray - "target lesion" on CXR d/t central area of necrosis surrounded by hemorrhage or edema |
| Opportunistic Mycoses: Zygomycosis | in poorly controlled diabetics; broad rarely septate hyphae of uneven width; Rhincerebral Zygomycosis (central facial swelling a/w dermal discoloration; purulent nasal discharge; conjunctival swelling (chemosis); proptosis (unilat); dec consciousness |
| Opportunistic Mycoses: Malassezia furfur | disseminated infxn only seen in pt on intravenous lipid hyperalimentation solutions |
| Opportunistic Mycoses: Pneumocystis carinii | humans use cholesterol in membranes; all pathogenic fungi use ergosterol EXCEPT P. carinii; "foamy" eosinophilic material in alveolar space; can progress to diffuse alveolar damage (acute resp distress syndrome); nodes, spleen, liver, marrow, eye; death |
| Opportunistic Mycoses: Cryptocossus neoformans | common in pigeon feces |
| Differential Dx of Fungal Infx based on site of infx: Pneumonia - Healthy Patient | Histoplasmosis, Blastomycosis, Cryptococcosis |
| Differential Dx of Fungal Infx based on site of infx: Pneumonia - Immunodepressed | Aspergillosis, Pneumocystis carinii, Zygomycosis |
| Differential Dx of Fungal Infx based on site of infx: Meningitis (regardless of immune status) | Cryptocossosis, Candida |
| Differential Dx of Fungal Infx based on site of infx: Disseminated - Healthy Patient | Histoplasmosis, Blastomycosis, Coccidioidomycosis |
| Differential Dx of Fungal Infx based on site of infx: Disseminated - Immunodepressed | Candida, Aspergillus, Cryptococcus, and most other fungi |
| Fungal Hyphae - Aspergillus | uniform width, acute <90degree angle, no septation |
| Fungal Hyphae - Zygomycosis (mucormycosis) | variable width, right angle branching, infrequent septation |
| Fungal Hyphae - Candida | uniform width, variable branching, no spetation (only constrictions present) |
| Transient Viral Infections | measles, mumps, polio virus, west nile, viral hemorrhagic fever |
| Chronic Latent Viral Infections | Herpes Simples, Cytomegalovirus, Varicella Zoster |
| Chronic Productive Viral Infections | Hepatitis, transforming infxns, Epstein-Barr virus, Human papillomavirus |
| Case: Measles | 12yo female, ill for 3 days (non-productive cough, runny nose, photophobia, fever, limited rash), red/white/blue spots in mouth concentrated around Stenson's duct; |
| Measles (Rubeola) | highly contagious via respiratory droplets; Koplik spots/Warthin-Finkeldey cells = Pathognomonic |
| Measles: time course | 10 day incubation; Day 8 (start of 3-4 day prodrome), Day 10 (Koplik spots; Rash, down and out - intense red, flat Tcell response); Infective until rash is gone...Leukopenia, proteinuria, WBC <2000 is poor prognosis |
| Measles: can also result in... | pneumonia, croup, diarrhea, myocarditis, keratitis w/scarring and blindness, encephalitis (10% fatal; SSPE - subacute sclerosing panencephalitis that develops over years |
| Mumps | #1 cause of pancreatitis in kids; incubation period of 14-21 days; Spead via saliva and urine; Facial swelling over parotid gland; painful; Orchitis - intense pain 25-40%; can also cause myocarditis, meningitis, encephalitis; Vaccine dec 99% of US cases |
| Mumps: DDx | parotid calculi; reaction to Iodides; Starch ingestion; Sarcoidosis; Sjogren's Syndrome |
| Polio | one of 5 subgroups of Enterovirus; 3 major strains, each covered with Salk and Sabin vaccines; Fecal-oral and pharyngeal secretions; Infects Peyer's patches of intestines and motor neurons; Vaccine dec to 0 in US; paralytic in 1950s |
| Polio: manifestations | 1. Mild - asympt to mild fever (most common); 2. Aseptic Meningitis - fever/meningitis recover in 1wk; 3. Paralytic poliomyelitis - pre and post synaptic anterior horn neurons (fever followed by flaccid paralysis 5-10 days; life long probs/death) |
| Viral Hemorrhagic Fevers | systemic infxns w/fever and hemorrhage (thrombocytopenia and platelet dysfxn); No cures or therapy; Potential biologic weapon d/t morbidity and mortality |
| Herpes Simplex (HSV-1, HSV-2) | reactivation w/ or w/o symptoms; results in spread from neurons to the skin and mucous membranes; HSV-1 causes corneal blindness (also fatal temporal lobe encephalitis) |
| Herpes: Morphology | cowdy type A inclusions; pushes host chromatin to edges; multinucleated ( |
| Herpes: Presentation | fever blisters/cold sores; Gingivostomatitis (HSV-1, kids, tongue/retropharynx/cervical lymphadenopathy); Genital herpes (transmission at birth can be bad); Herpes esophagitis; Corneal lesions; Encephalitis; Herpes bronchopneumonia |
| Cytomegalovirus | B-group herpes virus; varied disease (age and immune status); asymptomatic or mono-like illness in healthy pts; Devastating systemic infxn in neonates and immunocompromised |
| CMV: Transmission | Transplacental (congenital); breast milk, cervical or vaginal secretions during birth, saliva esp in daycare, venereal/fecal-oral/respiratory; organ or blood transfusion; Can hide from and suppress the immune system |
| CMV: Infections - Congenital | 95% asymptomatic; CID (cytomegalic inclusion disease) w/ growth retardation, erythroblastosis fetalis; anemia; thrombocytopenia, encephalitis, fatality |
| CMV: Infections - Perinatal Infxns | most asymptomatic; may develop interstitial pneumonitis; FTT; skin rash; hepatitis |
| CMV: Mononucleosis | nearly always asymptomatic; similar to that caused by EBV; 50-100% of adults have anti-CMV Abs; Most common is mononucleosis-like illness (fever, lymphadenopathy, hepatomegaly) |
| CMV: In immunocompromised pts | solid organ transplants from + donors; Allogenic bone marrow transplants; AIDS pts (CMV is most opportunistic viral pathogenin AIDS) |
| CMV: Life threatening infxns | Lungs (pneomonitis) can progress to ARDS; GI tract (colitis) pseudomembranes and debiliating diarrhea; Retina (retinitis) |
| Varicella Zoster Virus (VZV) | 1. Chichen pox (acute infxn); 2. Shingles (reactivationof latent infxn; aka: Herpes zoster) |
| Chicken pox | rash 2 wks after exposure; central to periphery; macule to vesicle |
| Chronic Productive Infxns: Hepatitis B | significant cause of acute and chronic liver disease; DNA virus w/multiple modes of transmission (IVDA, transfusion, perinatally, sexually); Infects Hepatocytes - damage occurs from immune response NOT cytopathic effect of virus; |
| Transforming Infections: | a group of viruses implicated in the causation of human cancer: EBV, HPV, HTLV-1 |
| Epstein-Barr Virus (EBV) | causes infectious mononucleosis; benign, self-limited lymphoproliferative disorder; fever, lymphadenopathy, splenomegally, sore throat, hairy leukoplakia, lymphomas, nasopharygeal carcinoma |
| Epstein-Barr Virus: transmission | via close human contact; envelope glycoprotein binds to CD21 (complement); infxn begins in tonsils; WBC 12-18,000 w/60% atypical lymphocytes; |
| Prion Diseases: TSE (transmissible spongiform encephalopathies) | Fatal neurodegenerative disorders, abnormal form of host protein - disease occurs when it undergoes a conformational change that results in resistance to proteases; accumulation of abnormal form results in neuronal damage and spongiform changes in brain) |
| Prion Diseases: Creutzfeldt Jakob Disease (CJD) | very rare; 85-90% of all prion cases; rapid progressive dementia; 85% sporadic; peak age 70 - fatal in 7months |
| Prion Disease: Kuru | Fore population in Papua New Guinea d/t ritualistic cannibalism |
| Prion Diseases: others | Gerstmann-Straussler-Scheinker Disease and Fatal Familial Insomnia (FFI) |
| Prion Animal Diseases: Scrapie | sheep and goats |
| Prion Animal Diseases: BSE (bovine spongiform encephalopathy) | Mad Cow Disease; Transmission to cows from feeding on infected sheep; humans eat infected cows; There is no known sheep to human transmission; Hallmark symptoms: abnormal posture, difficulty standing, weight loss |
| Prion Disease: Signs and Symptoms | all are similar: rapidly progressive dementia, psychiatric symptoms, cerebellar symptoms (ataxia), involuntary movements, ultimately FATAL |
| Prion Disease: Pathology | micro is pathognomonic; spongiform transformation of cerebral cortex and deep gray matter; small uneven vacuoles w/ no inflammatory infiltrate |
| Bacterial infections: Gram Positive | Staphylococcal, Streptococcal, Diptheria, Lysteriosis |
| Bacterial Infections: Gram Negative | Neisserial, Whooping Cough |
| Bacterial Infections: Mycobacteria | Tuberculosis, Mycobacterium Avium intracellulare |
| Bacterial Infections: Obligate Intracellular Bacteria | Chlamydial, Rickettsial |
| Bacterial Infections: Anaerobic | Syphilis, Lyme Disease |
| Bacterial Infections: Spirochetes | Abscesses, Clostridial |
| Staph Infection: 3 Major Pathogenic Species | S. aureus (not normal skin flora), S. epidermidis (normal skin flora), S. saprophyticus |
| Staph infection: Coag +, Gram +, Clustered cocci | S. aureus |
| Staph infection: Coag -, G +, clustered | S. epidermidis or S. saprophyticus |
| Staph Aureus: general | skin and soft tissue infxn: localized erythema and induration; abscess formation; culture of wound yields organism; if symptoms suggest systemic infxn, do a blood culture; potential for endocarditis and osteomyelitis |
| Staph Aureus: osteomyelitis | pathogen in 60% of cases; commonly d/t hematogenous spread; long bones; look for fever and back pain; prolonged therapy required (4-6wks) |
| Staph Aureus: Bacteremia | readily invades the blood stream...MUST consider endocarditis and osteomyelitis |
| Staph aureus: Scalded skin syndrome | aka: Ritters disease; most common in kids w/nasopharynx or skin infx; sunburn rash all over w/bullae; split of bullae in granulosa layer; NOTE: split of TEN (toxic epidermal necrolysis or Lyell's disease) from drug hypersensitivity is at derm/epiderm jxn |
| S. aureus: Toxic Shock Syndrome | abrupt onset of N/V/D, high fever, sore throat, myalgias, headache; dec BP, renal/cardiac failure are BAD signs; 15% fatal; 90% women; non-menstrual as common as menstrual cases |
| S. aureus: Enterotoxin food poisoning | d/t release of superantigens stimulating T-lymphocytes; massive cytokine release; vomiting, capillary leaks, shock; NOTE: blood cultures are NEGATIVE b/c symptoms d/t toxins and not organ invasiveness! |
| S. aureus: Direct Organ Invasion | pneumonia, meningitis, cerebritis, brain abscess; osteomyelitis; actue endocarditis; septic arthritis (most common cause of arthritis in kids and >50); skin infxn; bacteremia/sepsis |
| S. arueus: MRSA | most staph are PCN resistant b/c they secrete PCN-ase; Methicillin, Nafcillin and others will kill most staph b/c they are not broken down by PCN-ase; MRSA strains have acquired multi-drug resistance at hospitals; Vancomycin = choice drug for MRSA infxns |
| Staphylococcus: Coagulase Negative | S. epidermidis, S. haemolyticus, S. saprophyticus; rarely present w/o IV or prosthesis; ALL are normal skin flora; Must determine if infx is from foreign body or from contamination (75%); multiple strains isolated |
| Streptococcus: divided into 3 groups | based on ability to hemolyze RBCs |
| Strep: Beta-hemolytic | completely lyse RBCs; clear ring |
| Strep: Alpha-hemolytic | partially lyse RBCs; green hue |
| Strep: Gamma-hemolytic | no lysis of RBCs; aka non-hemolytic |
| Strep: the 5 human pathogenic species | Group A, Group B, Group D, Strep pneumoniae, Viridans group Strep |
| Strep: Group A Beta-hemolytic | S. pyogenes; causes 4 types of acute disease by local invasion or exotoxin release |
| **Strep: Group A Beta-hemolytic: Strep. pharyngitis | aka: strep throat (red swollen tonsils w/purulent exudates, high fever swollen lymph nodes; Tx: Penicillin) |
| **Strep: Group A Beta-hemolytic: Strep. pyogenes | skin infxn; necrotizing fasciitis; aka: flesh eating strep; bacterial rapidly move thru tissue following fascia; 24hrs, swelling, heat, redness; next day skin red/blue w/large blisters; needs surgical removal of fascia; rapid Ab's; 50% fatal |
| **Strep: Group A Beta-hemolytic: Scarlet fever | most common btw 3-15yo; associated w/tonsilitis; rash over trunk and inner arms/legs; spares mouth if on face |
| **Strep: Group A Beta-hemolytic: Toxic shock syndrome | similar to staph infxn |
| **Case example: TSS d/t Strep anginosus | group F normal flora; producing SPEA (strep pyrogenic exotoxin A) usu from Group A strep |
| **Group A Strep Delayed Disease: Post-streptococcal glomerulonephritis | can occur after strep THROATor SKIN infxn; 1 wk after infxn; classic...kid comes in 1wk after sore throat w/swollen face; Coke-colored urine; high BP |
| **Group A Strep Delayed Disease: Rheumatic Fever | kids 5-15; rare now d/t PCN; follows untreated strep Throat NOT Skin infx; 6 manifestations (Jones - Joint swelling, myocarditis, subcut nodules, erythema marginatum, sydenham's chorea); risk of rheumatic heart yrs later (mitral/aortic valves) |
| **Group B beta-hemolytic Strep: Strep agalactiae | cause neonatal disease (<3mo); meningitis; fever, N/V, poor feeding, irritability; must act fast; lumbar puncture; pneumonia; NOTE: one of most common baby bugs for meningitis |
| 3 most common bugs for baby meningitis | E. coli, Listeria, Group B strep |
| Viridans Group alpha-hemolytic Strep | causes 3 types of infxns: Dental (S. mutans), Endocarditis (SBE), Abscesses; NOTE: if found in blood culture, do a CT and look for organ abscess (S. intermedius) |
| Group D alpha-hemolytic Strep: Enterococci | S. faecalis and S. faecium; cause UTIs, biliary tract infxns and SBE |
| Group D alpha-hemolytic Strep: Non-enterococci | S. bovis; 50% of people w/S. bovis infxn have a colonic malignancy; BOVIS in BLOOD = Cancer in Bowel! |
| Strep pneumonia alpha-hemolytic | major cause of pneumonia/meningitis in Adults (sudden; yellow-green sputum); Xray - white consolidation, lobar; (otitis media in kids; no Lancefield antigens; paired cocci; Ouellung rxn (rapid ID) and Optochin sensitivity tests (inhibited growth); |
| Diptheria | corynebacterium; G+ rods; peds infxn; DON'T scrape off lesion b/c it'll bleed; releases powerful exotoxins (damages heart/neural cells)! Aerosol transmission; DPT immunization protects against toxic effects |
| Listeriosis: 5 types of infxn | 1.3rd trimester (fever-->spont abort); 2. Granulomatosis infantisepticum (in utero; abscess/granulomas/death); 3. Bactermia (w/ or w/o spesis; neonates/immunocomp); 4. Meningitis (#3 in infants; #4 adults); 5. Focal infxn, adenitis (brain, heart, bone) |
| Anthrax | large, boxcar-shaped G+ extracellular bacteria in chains |
| Neisserial infxn | the ONLY G-negative cocci (diplococci); 2 sp cause disease in humans: N. meningitidis (meningococus) and N. gonorrhoeae |
| N. meningitidis: high risk groups | infants (during Ab-free period; 6mo - 2yrs); Army recruits, college students (13 serotypes, first time exposure w/ long hrs of physical stress; asymptomatic in nasopharynx) |
| N. meningitidis: pathology | invasion of bloodstream results in meningococcemia; can Dx from across room, but it's too late (Petechial rash - d/t endotoxin release; spiking fever/chills/arthraglia/myalgia; 10% mortality), Bilat adrenal hemorrhage (Waterhouse Friderichson Syndrome) |
| Neisseria gonorrhoeae | aka: gonococcus; 2nd most common STD behind chlamydia; pili adhere to host cell and prevent phagocytosis; |
| N. gonorrhoeae: Women | painful urination and discharge, but usu asymptomatic and contagious; Cervical infx can lead to PID (uterus, tubes, ovaries; fever/abd pain/cervical motion tenderness; serious complications sterility/ectopic preg/abscess/peritonitis); Peri-hepatitis |
| N. gonorrhoeae: Men | penetrates mucous membranes of urethra causing urethritis; some men asymptomatic; painful urination w/discharge; contagious whether symptomatic or asymptomatic; (both men and women can have gonococcal bacteremia) |
| Whooping cough | Bordetella Pertussis; G-negative coccobacillus; vaccine in US; death in others; colonizes bronchi and invades macrophages; severe cases result in mucosal erosion, hyperemia, mucopurulent exudates; attaches to ciliated cells and destroys them |
| Pseudomonas aeruginosa | infects the sick and immunocomp hospital pts; resistant to most antibiotics; obligate aerobic G-negative rods; green discoloration on bandage; smells sweet - grape-like; healthy people don't get this |
| Bubonic Plague: Yersinia pestis | 1/4 pop Europe died in 1300s; San Fran in 1900s; contact w/dead animal or infected flea bite; invades skin, then macrophages; >1wk lymph node swelling/red/painful/hot; headache/fever; skin hemorrhage black color; AZ/NM campers w/fever!! Tx: Gentomycin |
| Chancroid | Hemophilus ducreyi; STD most commonly affecting lower social economic groups (prostitutes); 3-5day incubation; painful genital ulcer; 50% unilat painful swollen lymph node; aggregated lymph nodes rupture and release pus; Tx: Erythromycin |
| Granuloma Inguinale | Calymmatobactyerium Donovani; STD; tropical, 8-12 week incubation; purulent painful foul-smelling lesion very hard to treat; lymph obstruction causes elephantiasis of external genitals; Histo Patognomonic: intracellular cysts w/ Donovan bodies; Wright's + |
| Mycobacteria | 2 Sp infecting humans: M. tuberculosis and M. leprae; thin rods, lipid walls, acid fast + |
| Tuberculosis | #1 infectious cause of death worldwide after HIV; 10 mill case/yr; 45% of US cases are immigrants; inc d/t AIDS b/c 1/3 of all HIV pts have TB; general risk is 10%; grows slowly; primarily affects lung tissue; Infxn doesn NOT = disease!! |
| Primary Tuberculosis | very 1st exposure; lower upper or upper lower airways; cell mediated immunity walls off bacteria; defeated bacteria lay dormant; small area of pneumonitis; enters macrophages and spreads via lymph and blood to LN and distant organs |
| Primary Tuberculosis: Asymptomatic primary infxn | Cell-mediated defense; bacterial walled off in caseous granuloma; Granulomas heal w/Ca scars; organisms decrease in #, but are still viable; Ca-tubercle called: Ghon focus |
| Primary Tuberculosis: Symptomatic primary infxn | less frequent; more common in kids, elderly, HIV pts |
| Secondary Tuberculosis | can occur in any organ that was seeded in primary infxn; temporary weakening of immune system precipitates reactivation; |
| TB: Ghon complex | the combo of parenchymal lung lesion (ghon focus) and nodal (hilar) involvement |
| TB: PPD Skin test (Mantoux test) | Positive PPDs seen in: active, latent and cured TB infxns; BCG pts (false +, Bacillus Calmette-Guerin vaccine for atypical mycobacteria, sarcoidosis, HD) |
| TB: PPD false negative | some don't react even if exposed in past; these pts are ANERGIC and lack normal immune response (steroid use, AIDS, malnutrition) |
| TB: systems affected | Pulmonary (most common; apices of lung, grow caseate, liquefy, cavitate, low grade fever/night sweats/wt loss/cough blood); Pleural and pericardial; lymph nodes; kindeys; bone/joints (Pott's Dx); CNS; Miliary |
| TB: Important points | a chronic disease that presents slowly w/symptoms related to the organ system affected; slow course may be confused w/ cancer; whenever you have an infxn of any organ system, TB should be in DDx! |
| TB: Rule of Fives | Droplet nuclei 5um and contain 5 bacilli; 5% reactivation risk; HIV will have 5 +5% risk of reactivation per year; HIV positive skin test is 5mm |
| Mycobacterium Avium - Intracellulare Complex | MAC or MAI; usu only infects birds but common in AIDS as a major systemic infxn; only strikes when Tcell count is very low; Results in chronic wasting and chronic watery diarrhea |
| Spirochetes: 3 important diseases | Gram-negative, slim cork-screws; Syphilis; Relapsing Fever; Lyme Disease |
| Spirochetes: Syphilis | treponema pallidum; chronic venereal disease w/multiple clinical presentations; STD; crosses placenta; active during pregnancy results in congenital syphilis; no toxins or destructive enzymes; Host immune response causes manifestations |
| Spirochetes: Syphilis epidemiology | 100,000 new cases/yr; black urban pop inc #s; enters body thru skin contact (even intact); *Even a Dr's infected hand could cause infxn; Spirochetes spread immediately thru body; 3 Stages if untreated |
| Spirochetes: Syphilis 3 Stages | 1. Latent: sero+ w/o symptoms; 25% relapse to 2* phase; after 4 years, no more relapses/non-infectious EXCEPT in pregnant women; 1/3 become 3*; 2/3 remain asymptomatic |
| Spirochetes: Syphilis - Stage 1 | chancre; painless, highly infectious |
| Spirochetes: Syphilis - Stage 2 | palmar rash, lymphadenopathy, condyloma latum; painless wart |
| Spirochetes: Syphilis - Stage 3 | Neurosyphilis (meningovascular/tabes dorsalis/general paresis); Aortitis (aneurysms/aortic regurgitation); Gummas (hepar lobatum/skin, bone, others) |
| Spirochetes: Syphilis - Congenital | Late: abortion/stillbirth; Infantile: rash, osteochondritis, periositis, liver/lung fibrosis; Childhood: interstitial keratitis, Hutchinson teeth, CNVIII deafness |
| Syphilis: labs | inc bacteria, inc PMNs, inc protein, dec glucose; TB and syphilis cause inc lymphocytes |
| Syphilis: Serologic Screening Tests: Non-specific | VDRL (venereal disease research lab) and RPR (rapid plasma reagent); screening; Abs against cardiolipin and licithin (both released during infxn w/cell damage); False + in PG, IVDA adn after immunization; Must confirm + w/specific test |
| Syphilis: Serologic Screening Tests: Specific | FTA-ABS (fluorescent treponemal antibody w/absorption); tests for antibodies against spirochetes |
| Syphilis: Serologic Screening Tests: Active Infection | (+) VDRL or RPR and (+) FTA-ABS |
| Syphilis: Serologic Screening Tests: Fals Positive | (+) VDRL or RPR and (-) FTA-ABS |
| Syphilis: Serologic Screening Tests: Successfully Treated | (-) VDRL or RPR and (+) FTA-ABS |
| Syphilis: Serologic Screening Tests: Syphilis unlikely except in early infxn or AIDS | (-) VDRL or RPR and (-) FTA-ABS |
| Nocardia asteroides | aerobic, gram-positive, acid-fast +, branched chains; found in soil; opportunistic infxn; Pulmonary involvement (malaise/fever/night sweats/cough purulent sputum/may develop pleural effusions), brain abscess and subcut nodules; Tx for >6 months |
| Hereditary and Developmental Bone Disorders (constitutional disorders of bone): Primary | dysostoses, osteochondrodysplasias |
| Hereditary and Developmental Bone Disorders (constitutional disorders of bone): Secondary Dysplasias | more common than inherited skeletal dysplasias; Common Acquired Dysplasias are d/t: Paraplegia, Quadriplegia, Chronic Inactivity from chronic disease (leukemia, juvenile chronic arthritis, hemophilia, cerebral palsy, neuromuscular diseases) |
| Most common skeletal dysplasias | achondroplasia, multiple epiphyseal dysplasia, osteogenesis imperfecta, thanatophoric dysplasia, Marfans disease, Gauchers disease, neurofibromatosis... |
| Skeletal Dysplasias: General Clinical Course and Sequelae | few a/w stillbirth or death shortly after; marked inc in scoliosis/degenerative joint disease; almost all a/w reduced life-span/functional disabilities |
| Achondroplasia: Genetics | almost all are Sporadic (de novo); point mutations in FGFR3 at 4p16.3 |
| Achondroplasia: Clinical Synopsis | normal trunk length with shortened limbs (rhizomelic shortening of proximal segments) present at birth |
| Achondroplasia: Clinical Course and Sequelae | inc incidence of forament magnum stenosis leading to: hydrocephalus/compression of brainstem or upper cervical spinal cord/ataxia/incontinence/central apnea; Increased incidence of spinal canal stenosis |
| Multiple Epiphyseal Dysplasia: Pathophysiology | disorganized endochondral ossification; epiphyseal cartilage cells are irregular w/disordered columns and areas of degeneration; epiphyseal ossification ctrs delayed w/abnormal fragments; WB joint degeneration |
| Multiple Epiphyseal Dysplasia: Clinical Synopsis/Course and Sequelae | short limbs in relation to trunk; usu rhizomelic shortening; multiple skeletal deformities d/t abnormal growth (coxa vara - hip; genu valgum - knee; genu varum - knee); early onset OA in WBJ; inc incidence of avascular necrosis of hip |
| Osteogenesis Imperfecta: Genetics | usu auto dom (some de novo); mutations in any one allele in genes for COL1A1/COL1A2 retards formation of normal Type I collagen (similar to thalassemias); Phenotypic heterogeneity - multiple types w/variable presentation from diff combo of defects |
| Osteogenesis Imperfecta: Pathology | Type I collagen is predominantly found in bone and fibrous tissue; defects result in thin trabecular bone a/w thinning of CORTEX |
| Osteogenesis Imperfecta: Clinical Synopsis | all cases present at birth or during infancy; multiple fractures/easy bruising/abnormal teeth (dentinogenesis imperfecta) |
| Osteogenesis Imperfecta: Type I | auto dom; defect in one of 2 genes results in mild dec in type I collagen; generalized osteoporosis; NORMAL STATURE; no deformities; hearing loss; minimal propensity to fx |
| Osteogenesis Imperfecta: DDx and Clinical Course/Sequelae | Inflicted injury as in Child Abuse; depends on clinical type (Type II is most severe); Types III (blue sclera) and IV have reduced life expectancy d/t inc respiratory infxns from rib fxs/progressive kyphoscoliosis |
| Osteogenesis Imperfecta on the Boards!! Structural ptns and the dom negative allele effect | Type II OI is Dom Neg Allele b/c mutated product has neg effect on non-mutated Col-I; d/t multi-unit nature of normal final product (Type I col) & illustrates how Dom Neg mutants in multimeric ptn account for auto dom inheritance pattern |
| Osteogenesis Imperfecta on the Boards!! DDx Blue Sclera | Osteogenesis Imperfecta Type III; Turner Syndrome; Paget Disease; Osteopetrosis |
| Neurofibromatosis Type I: Genetics and Pathophysiology | Auto Dom; NF-1 is tumor suppressor anti-oncogene on 17q11.2 encodes neurofibromin G-ptn that inhibits ras (aka: p21); NF-1 mutation allows uncontrolled ras-induced proliferation of neural crest cells (melanocytes/neurons/schwann cells); few w/complete LOF |
| Neurofibromatosis Type I: Clinical Synopsis | variable phenotype; childhood onset; multiple benign neurofibromas (admix fibrous/neural tissue) from periph nerves in skin/bone/organs; >5 cafe au lait spots along course of peripheral nn; bone (focal dysplasia/fibrosis/cystic lesions) |
| Neurofibromatosis Type I: Clinical Course and Sequelae | inc incidence of learning disability and ADD; scoliosis esp in F; neurofibrosarcoma transformations; inc CNS neoplasms (bilat optic n gliomas); soft tissue sarcomas; chronic myeloid leukemia; pheochromocytomas (manifest hypertension) |
| Marfan Syndrome: Genetics and Pathophysiology | auto dom; Fibrillin structural component of microfibrils which accompany elastin; mutation in FBN1 disrupts microfibril formation from normal allele (Dom Neg Effect) |
| Marfans Syndrome: Clinical Synopsis | tall w/long limbs (dolichostenomelia); ligament laxity/hypermobility (recurrent subluxation/joint injury); medial necrosis of aorta=dilation and dissection; mitral/aortic valve sclerosis and prolapse; pectus excavatum; scolios; lens dislocation |
| Marfans Syndrome: Clinical Course and Sequelae | inc incidence of scoliosis, mitral valve sclerosis and prolaps; aortic valve regurgitation; aortic dissection/rupture leading to sudden death |
| Glucoserebrosidases: Type I Gaucher Disease | marked predilection for Ashkenazi Jews; auto rec gene for beta-glucosidase on 1q21.31; multiple mutations all w/some functional enzyme activity (polymorphism variable phenotype); Mutations in type 2 and 3 abolish enzyme fxn leading to more severe symptoms |
| Glucoserebrosidases: Pathophysiology | glucosylceramide accumulates in: bone marrow/liver/spleen/lungs; presence of Gaucher cells in macrophage/monocyte - enlarged "wrinkled" stain PAS+ (periodic acid-Schiff) |
| Glucoserebrosidases: Clinical Synopsis | pancytopenia d/t marrow failure (enlarged macrophages): anemia/fatigue; thrombocytopenia/bruising; extramed hematopoiesis; hepatomegaly d/t Kupffer cell phagocytic accum/obstruction of blood flow/non-chirrotic portal hypertension/UGI bleeds |
| Glucoserebrosidases: Clinical Synopsis Continued | hepatocytes DON'T accumulate glycosylceramide; splenomegaly; diffuse infiltrative pulmonary dx leading to SOB; chronic bone pain; pathological fx of WB bones and/or ribs; immune deficiency leads to inc incidence of serious infxns |
| Glucoserebrosidases: Type I Gauchers Disease | only 30% of pts become symptomatic in childhood (the rest may present in adulthood); most common genetic disorder in Ashkenazi (eastern eruopean) Jewa |
| Glucoserebrosidases: Type I Gauchers Disease - Radiological Findings | bone changes = skeletal dysplasia; d/t progressive infiltration of Gaucher cells in marrow; generalized osteopenia/thinning of cortex; Erlenmeyer flask distal femur; bone infarction (pain/swelling/osteomyelitis-Gaucher crisis; osteosclerosis; collapse) |
| Glucoserebrosidases: Type I Gauchers Disease - Radiological Findings Continued | osteosclerosis (like sickle cell pattern) in: femoral head/distal femur/proximal tibia/proximal humerus; joint dysfxn collapse occurs at articular surface if subchondral infarction; lytic-fx lesions long bones/vertebrae/ribs/pelvis d/t Gaucher cell pop |
| Mucopolysaccharidoses | grp of 11 lysosomal storage disese d/t disorder in GAG metabolism (aka:mucopolysacc); results in abnormal presence in urine/infiltration in CT leading to defects in bone/cartilage/organs |
| Mucopolysaccharidoses: Pathology | defective acid hydrolases (no GAG degrad); accum esp skeleton; progressive; inhibits normal growth; damages tissue; cytoplasmic inclusions (esp leukocytes/hepatocytes/neurons) - metachromic granules; dysostosis multiples; hepatosplenomegaly; CT; brain |
| Mucopolysaccharidoses: Clinical Synopsis | progressive; MR; thick/inelastic skin; hepato dysmorphic features (coarse face/big head gargoyle like); dysostosis multiplex (short stature; gibbus deformity-throacolumbar kyphoscoliosis hump and flat vertebral bodies); hepatosplenomegaly |
| Mucopolysaccharidoses: Clinical Synopsis continued - dyostosis multiplex | hypoplasia of pelvis/femoral heads; oar-shaped ribs (narrow at vertebrae); diaphyseal/metaphyseal expansion of long bone w/cortical thinning; tapered proximal phalanges; macrocephaly; dislocatd hip; joint contractures; odontoid hypoplasia |
| Mucopolysaccharidoses: General Laboratory Diagnosis | granulocyes may exhibit Alder-Reilly granulations (coarse characteristic of MPS); peripheral lymphocytes may exhibit metachromatic granules w/in vacuoles |
| Mucopolysaccharidoses: Type IV (aka: Morquio Syndrome) | block in keratin sulfate (and chondroitin sulfate) breakdown; spared MR/other diseases d/t sparing of heparan/dermatan sulfate |
| keratin sulfate | mostly found in cartilage and cornea |
| heparan and dermatan sulfate | more generalized tissue distrubution |
| Mucopolysaccharidoses: MPS Type IV - Clinical Synopsis | usu present d/t skeletal deformities in young child; NO abnormal facies; NO MR; short trunk dwarfism; inc atlantoaxial instability d/t odontoid hypoplasia and acute/chronic cervical compression myelopathy; ligamentous laxity |
| Mucopolysaccharidoses on the Boards!! Type IH (Hurler Syndrome) | has shortest life-span of MPS w/ most pts dying in late childhood |
| Mucopolysaccharidoses: Type II MPS (Hunter Syndrome) | the ONLY MPS that is NOT auto recessive in inheritance |
| Mucopolysaccharidoses: Severe MR associated with: | Type IH, Type II, Type III |
| Mucopolysaccharidoses: Type IS (Scheie Syndrome) | the only MPS w/ a normal life-span |
| Osteopetrosis | hereditary bone dx of heterogeneous pathophysiology w/osteoclasts failing to reabsorb bone; leads to disruption in normal remodeling of woven bone into compact bone; results in dense/fragile/brittle bone; disrupts normal Ca and phosphate metabolism |
| Osteopetrosis: Lab Dx, Clinical Course/Sequelae | elevatd alk phos and parathyroid hormone; inc incidence of fx; osteomyelitis (d/t derangements in blood supply from abnormal remodeling esp in mandible; infantile type = low life expectancy d/t bone marrow failure |
| Craniorachischisis: Spina Bifida Occulta (Rachischisis Posterior Occulta) | mildest form; present in 10% of healthy pop; can be anywhere along spine but common at lumbosacral jxn; usu only one vertebral body; incomplete fusion of R/L half of posterior elements; NO spinal cord/membanes; most asymptomatic; may have spondylolithesis |
| Limb Reduction Defects: pathophysiology | 1. Idiopathic - most common; 2. Exogenous Agent (thalidomide/warfarin/methotrexate/hydantoin/Bendectin/Accutane/cyclophosphamide/pesticides; 3. Endogenous (blood loss to part: amniotic band; maternal meth tetrahydrofolate recuct def; diabetes; varicella) |
| Ollier's Disease: Genetics and Pathophysiology | most are congenital, but NOT hereditary; multiple circumscribed foci/masses of cartilage in interior of bone (long/short tubular extremities; NOT skull/spine) |
| Ollier's Disease: Clinical Synopsis/Course and Sequelae | youth onset; many bone deformities d/t ectopic intraocceous cartilage nests (swelled fingers/toes/long bone metaphysis/pelvis; leg discrepancies d/t disruption of normal growth; cartilage ossifies by puberty/pathological fxs; sarcomatous transformation |
| Osteoporosis | bone mass loss (demineralization usu d/t loss of gonadal fxn; fragility and inc fx risk; |
| Osteoporosis: Risk Factors | poor bone mass acquisition during growth (peak 20-30yo) - main factor is genetic; accel adult bone loss (dec estrogen/testosterone/Ca, VitD, ptn, calorie intake); lack of physical activity; smoking; chronic EtOH/CCsteroid use |
| Osteoporosis: Pathophysiology of Type I | d/t gonadal hormone deficiency which effects osteoclastic activity; Estrogen/Testosterone |
| Osteoporosis: Pathophysiology of Type II | d/t advancing age regardless of gonadal hormones; dec formation of bone/renal production of VitD; loss of both cortical and trabecular bone |
| Osteoporosis: Pathophysiology of Type III | secondary to bed-rest and inactivity; secondary to medications (glucocorticoids (CCsteroid OP); heparin; anti-convulsants; chronic EtOH); secondary to other primary dx w/ bone loss (Cushing's syndrome) |
| Osteoporosis: Clinical Synopsis and Radiological Findings | chronic bone pain; acute back pain d/t vertebral body collapse; multiple fx d/t simple falls; generalized osteopenia; vertebral compression fxs |
| Osteoporosis: Biochemical markers for bone loss | all markers are type I collagen degradation products: Hydroxylysine (aa specific to bone); Tartrate-resistant acid phosphatase (isoenzyme only in bone) |
| Osteoporosis: Corticosteroid variant | taking CCsteroids for as little as 2 wks can result in symptomatic osteoporosis; CCsteroids cause osteoporosis by many mechanisms that inhibit osteoblasts and stimulate osteoclasts |
| Adult Paget Disease of Bone: Pathophysiology | exact pathogen unknown (viral? cytokine dysfxn?); usu only one bone (monostotic); inc # of osteoclasts leads to inc bone resorption and inc # of osteoblasts form new bone randomly; Dysplastic bone formation leads to thick and brittle bone |
| Adult Paget Disease of Bone: Lab diagnosis and Clinical Course/Sequelae | Normal Ca/phosphate/PTH; Elevated Levels indicative of bone turnover: Alk Phos and Hydroxyproline in urine; Spont remission is common; inc pathologic fx/OA/radiculopathy/giant cell bone tumor/malignant sarcomatous transformation - most common neoplasm! |
| Rickets: Nutritional | inadequate intake or activation of VitD; inadequate Ca and/or phosphate intake; hypocalcemia; hypophosphatemia; elevated PTH; in adults - leads to generalized osteomalacia (softening) a/w inc pathologic fxs; in children - osteomalacia a/w growth failure |
| Rickets: Familial Hypophosphatemia (formally VitD-resistant Rickets) - Pathophysiology | genetic proximal renal tubule defect (can't reabsorb phosphate/Phosphate wasting in urine - defective regulation of Na-phosphate cotransporter in epithelial brush border); can't normally ossify bone (impairs fxn of osteoblasts); Normal Ca levels |
| Primary Hyperparathyroidism: Synopsis | autonomous production of PTH by parathyroid glands; excessive osteoclastic activity and bone resorption; inc renal tubular absorption of Ca and loss of phosphate; Hypercalcemia; Hypophosphatemia |
| Primary Hyperparathyroidism: Common Causes | 1. Adenoma (usu solitary; Chief Cell Adenoma); 2. Diffuse gland hyperplasia; 3. Malignancy (very rare) |
| Primary Hyperparathyroidism: Clinical Synopsis | most pts symptomatic; fatigue, weakness; cognitive/emotional abnormalities; osteomalacia skeletal deformity and pathologic fx; nephrocalcinosis and nephrolithiasis dt high phosphate in urine; Shortened QT interval |
| Primary Hyperparathyroidism: Xray and Lab Findings | osteopenia; subperiosteal resorp (clavicles, distal phalanges, symphysis, v-bodies); salt-n-pepper skull; Hypercalcemia; Hypophosphatemia; Hypercholoremic acidosis (loss of bicarb; acidosis; Cl neutralizes fluids; Dehydration (hi Ca inhibits ADH ) |
| Primary Hyperparathyroidism: inhibition of vasopressin (ADH) leads to | acquired nephrogenic diabetes insipidus |
| Pimary Hyperparathyrodism: Variants - Multiple Endocrine Neoplasia Type I | aka: MEN Type I; auto dom; multiple endocrine glands show abnormality including parathyroid glands; hyperparathyroidism present in almost all pts |
| Pimary Hyperparathyrodism: Variants - Multiple Endocrine Neoplasia Type 2 | aka: MEN Type 2; only a small minority exhibit hyperparathyroidsm |
| Primary Hyperparathyroidism: Levels | Elevated: Serum Calcium and PTH; Decreased: Serum Phosphate |
| Secondary Hyperparathyroidism: Levels | Decreased: Serum Calcium; Elevated: PTH; Variable: Serum Phosphate |
| Hypoparathyroidism: Levels | Decreased: Serum Calcium and PTH; Elevateed: Serum Phosphate |
| Pseudohypoparathyroidism: Levels | Decreased: Serum Calcium; Elevated: PTH; Variable: Serum phosphate |
| Bone Infarction Vs. Avascular Necrosis | infarction - lesions in metaphysis and diaphysis; AVN - lesions in epiphysis |
| Bone Infarction: Risk Factors | traumatic injury; hyperlipidemia; systemic vasculitis (SLE, etc); Chronic CCsteroid use; Sickle Cell Disease; Diabetes mellitus; Chronic EtOH |
| Bone Infarction: Common sites and pathophysiology | sites susceptible to vascular infarct (femoral head, humeral head, scaphoid); dead bone becomes more radioopaque (dense) or radiolucent (cystic defeneration); repair by layers of new bone over infarcted nidus |
| Bone Infarct: Variants - Legg-Calve-Perthe Disease | usu unilateral osteonecrosis of prox femoral epiphysis and femoral head that collapses subarticular bone; *Articular cartilage is preserved; underlying cause is insufficient blood dt idiopathic ishcemia of ligamentum teres vessesl |
| Bone Infarct: Variants - Legg-Calve-Perthe Disease Clinical Course/Sequelae | most re-vascularize to some degree of recovery; Most exhibit morbidity a/w abnormally shaped, reconstituted femoral head (coxa plana, dysfxnl apposition of head in acetabulum); Inc incidence of OA |
| Degenerative Slipped Capital Femoral Epiphysis: Risk Factors | repetitive trauma, adolescent growth spurt; obesity; congenital hip dysplasia; chronic renal failure; ChemoRx |
| Degenerative Slipped Capital Femoral Epiphysis: Pathophysiology | sheer stress thru prox femoral epiphysis causes fx (probably dt an intrinsic weakness); chondronecrosis and osteonecrosis; rarely bilateral |
| Degenerative Slipped Capital Femoral Epiphysis: Clinical course | aseptic osteonecrosis of femoral head dt disruption of blood supply; inc incidence of OA |
| Bacterial Osteomyelitis | acute/chronic inflam of bone secondary to infxn w/pyogenic bugs; common in pts w/sickle cell or diabetes mellitus; fever, pain w/movement of extremity; erythema/swelling; Leukocytosis w/left shift; xray nml for 2wks; periosteal thickening/focal osteolysis |
| Bacterial Osteomyelitis: Hematogenous Acute Osteomyelitis | usu kids; S. aureus (mc), S. pyogenes; G-neg enterics; Salmonella in sickle cell pts; source of infxn distant from site of osteomyelitis w/route of infxn being bacteremia |
| Bacterial Osteomyelitis: Direct Acute Osteomyelitis | usu polymicrobial and in adults; infxn in bone secondary to inoculation of organisms from direct trauma, spread from contiguous focus of infxn (ex: joint space); surgical procedure |
| Bacterial Osteomyelitis: Chronic - Marjolin ulcer | a draining, fistulous tract that develops an aggressive squamous cell carcinoma (aka: epidermoid carcinoma) |
| Tuberculous Osteomyelitis | occurs in 1 of 40 pts w/primary pulmonary or primary GI tuberculosis; vertebral bodies/metaphysis of long bones; secondary spread from primary focus in bowel or lung; granulomatous inflam a/w caseous necrosis |
| Tuberculous Osteomyelitis: Clinical stuff | insidious symptoms but becomes acute w/progression of infxn; low fever; erythema/swelling; localized pain; contiguous spread to adjacent soft tissue/synovial joints; inc incidence of path fx |
| Tuberculous Osteomyelitis: Variants - Tuberculous Spondylitis | aka: Pott's disease; occurs in vertebral body; low fever, general malaise a/w chronic mild back pain; vertebral collapse fx; contiguous spread leads to tuberculous meningitis &/or myelopathy (aka: Pott Paraplegia) |
| Benign Bone Tumors: Fibrous Cortical Defect and Osteochondroma (mc) | more common than primary malignant bone tumors; usu in young pts; usu not painful; slow-growing over yrs; NOT destructive to adjacent bone (no inflam or reactive bone formation); no spread to soft tissue; |
| Risk Factors for Primary Bone Malignancy | hereditary cancer syndromes (Li-Fraumeni Syndrome); osteonecrosis; osteomyelitis; Paget disease of bone; post-radiation Rx; intra-osseous metal prosthetic devices |
| Malignant Bone Tumors: Osteosarcoma, Chondrosarcoma, Ewing's sarcoma | 1 in 150,000/yr; usu young pts; Rapid growth; painful; long bones of extremities; destructive inflam (cortical thinning, reactive new bone growth, preiosteal reaction); expansive infiltrates soft tissue; metastatic tumor is more common than primary |
| Osteoid Osteoma | <2cm; combo of non-calcified & woven bone w/inc osteocytes; usu male teens; constant pain inc w/activity; better at night; relief w/ASA; prolif of nerve fibers/E2 production cause pain; Xray (radioluc w/sclerotic (reactive) margin, central nidus) |
| Osteosarcoma | usu youth; distal femor/prox tibia (mc); humerus/skull/jaw/pelvis |
| Osteosarcoma: Risks | radiation Rx; Paget disease of bone; fibrous dysplasia; enchondromatosis; hereditary multiple exostoses; retinoblastoma (germ-line form); p53 mutation (Li-Fraumeni syndrome) |
| Osteosarcoma: Clinical synopsis | pain, esp w/activity; progressively enlarging mass; pathological fx |
| Osteochondroma | usu distal ends (metaphysis) of long bones; can involve any bone; usu isolated from surface of bone; boney exostosis w/cartilaginous cap |
| Osteochondroma: Clinical course | painful peri-articular swelling; may rarely impinge on adjacent nerves/vessels |
| Osteochondroma: Variant - Hereditary Multiple Exostoses | multiple cartilage-capped outgrowths in metaphyseal region of long bones; usu bilat and symmetric; usu point away from nearest joint; may be dt aberrant foci of misplaced epiphyseal cartilage w/growth aberrantly; transformation in multiple osteochondroma |
| Chondroma/Endochondromatosis Variants - Maffucci's Syndrome, Ollier's Syndrome, Metachondromatosis | the presence of multiple endochondromas w/a high malignant transformation to chondrosarcoma |
| Chondrosarcoma | usu pelvis, prox femur, prox humerus; arises from chondrocytes, but peripheral forms arise from surface of bone (usu pelvis); contral forms arise from medullary cavity (usu femur/humerus) |
| Chondrosarcoma: Clinical synopsis | Peripheral - rapid growth, palpable mass, pain; Central - presents w/pain or pathologic fx (asymptomatic turns up on routine CXR) |
| Chondrosarcoma: Clinical course | most are low-grade (Grade I) w/good prognosis; High-grade (III) have poor prognosis; A minority of benign cartilaginous neoplasms have ability to transform into chondrosarcomas w/time |
| Chondrosarcoma: Variants - Mesenchymal Chondrosarcoma | combo of undiff benign mesenchymal tissues (usu spindle cells) admixed w/malignant cartilage; slow-growth; high recurrence rate; minority occur w/o relation to bone (ex: Extraskeletal mesenchymal chondrosarcoma) |
| Fibrous Cortical Defect/Non-Ossifying Fibroma | usu in teens; juxtaepiphyseal/metaphysis region of long bones (Femur mc; tibia, fibula, humerus); benign solitary fibrous proliferation composed of spindle cells a/w gian cells and foamy histiocytes |
| Fibrous Cortical Defect/Non-Ossifying Fibroma: clinical course | most are asymptomatic, most migrate to diaphysis or resolve spontaneously; inc incidence of path fx depending on size and location of fibroma |
| Ewing Sarcoma of Bone | usu kids/teens; metaphysis or diaphysis of long bones of extremities or pelvis; probably arises from marrow stem cells; t(11:22) is present in most tumors - joins w/EWS gene on Chrom 22 and FLI1 (friend leukemia insertion) on Chrom 11 |
| EWS/FLI1 fusion transcript | encodes a protein that is a potent transcriptional activator which can turn normal cells into malignant cells |
| Ewing Sarcoma: Xray findings | osteolytic infiltrating neoplasm that extends into adjacent soft tissue; periosteal reaction usu present often w/onionskin or sunburst patter, which indicates an aggressive process |
| Ewing Sarcoma: Variants - Primitive neuroectodermal tumor (PNET) of bone | arises from same cell as Ewing Sarcoma, but differentiates in the neural direction; manifests the same cytogenetic abnormality as Ewing Sarcoma |
| Metastasis of Tumors to Bone: Osteoblastic/sclerotic malignancy | prostate |
| Metastasis of Tumors to Bone: Osteolytic | kidney, liver, thyroid |
| Metastasis of Tumors to Bone: Others | breast; usu osteolytic: lung; usu osteoblastic: colon, melanoma, bladder, soft tissu |
| Metastasis of Tumors to Bone: Clinical synopsis | bone pain very common; path fx is common |
| Congenital Hip Dislocation: Pathophysiology | NORMAL hip development a/w laxity of supporting structures allowing easy dislocationof femoral head over lip of acetabulum; maternal hormones can cross placenta to promote ligament laxity in neonate; usu left hip |
| Congenital Hip Dislocation: Clinical Course | most develop normally w/o Rx usu resolves by 8wks; first 6wks are critical for healthy joint formation; if dislocation is chronic the femoral head and acetabulum develop a dysplastic relationship; AVN common of femoral head later in life |
| Congenital Hip Dysplasia: Pathophysiology | may develop congenitally and be present at birth; may be part of generalized osteochondrodysplastic condition; may develop postnatally dt untreated congenital hip dysplasia |
| Foot Deformities: Congenital Talipes Equinovarus Pathophysiology | Clubfoot, uni/bilat; dt abnml position inutero; fixed-idiopathic (enterovirus harms ant horn of s.c.); more severe types a/w congenital neuromuscular/skeletal syndromes; short medial tendons/ligaments (supinate-varus/plantar flex-equinus) |
| Congenital Talipes Equinovarus: Associated syndromes | spina bifida, arthrogyposis, osteochondrodysplasia |
| Rheumatoid Arthritis | hands (MCP, PIP), feet, wrists; usu symmetric polyarthropathy; chronic systemic autoimmune inflammatory; may involve extra-articular structures |
| Rheumatoid Arthritis: Lab Diagnosis | RF (IgM autoantibody directed against Fc portion of IgG); most pts have circulating RF; others are seronegative; RF can also occur in other autoimmune diseases |
| Rheumatoid Artrhitis: Extraskeletal Diseases | subcut/rheumotoid nodules; Lung/pleural inflam (nodules in lung, interstitial dx, pleuritis); Heart (pericarditis, myocarditis, valvulitis); Vessels (systemic vasculitis); Bone (osteopenia) |
| Rheumatoid Arthritis: Extraskeletal Diseases - Felty's Syndrome | Rheumatoid arthritis, granulocytopenia, splenomegaly, recurrent infxns |
| Juvenile Rheumatoid Arthritis: Synopsis | inflammatory polyarthropathy in kids <16yo, lasting >90 days, other causes excluded, minority have evanescent exanthem (rheumatoid rash) |
| Juvenile Rheumatoid Arthritis: Pathophysiology | serum RF usu negative (member of seronegative spondyloarthropathies); onset of disease is frequently preceded by viral or bacterial infxn |
| Seronegative Spondyloarthropathies: Ankylosing Spondylitis | axial skeleton (vertebral column, sacroiliac joints, costovertebral joints); hips, shoulders; most pts are HLA-B27 positive; |
| Seronegative Spondyloarthropathies: Ankylosing Spondylitis - Pathophysiology | disorder of synovial and cartilaginous articulations of vertebral column and tendons/ligament insertion into bone; inflam of disk and articular fibrocartilage followed by fibrosis, ossification and akylosis (arthrosis); dt Klebsella pneumonia (HLA-B27 seq |
| Seronegative Spondyloarthropathies: Psoriatic Arthritis Synopsis | arthritis usu has onset years after onset of psoriasis in most pts; most pts w/psoriatic arthritis and spondylitis are HLA-B27 positive |
| Seronegative Spondyloarthropathies: Enteropathic Arthritis - Post Infectious/Reactive Arthritis Pathophysiology | acute nonpurulent arthritis following infxn elsewhere in body (ex: Shigella flexner, Salmonella, Yersinia enterocolitica, Campylobacter jejuni, Clostridium difficile gastroenteritis OR Clamydia, Ureaplasma urealyticum urethritis) |
| Seronegative Spondyloarthropathies: Enteropathic Arthritis - Post Infectious/Reactive Arthritis Clinical Synopsis | onset 1-3 wks after bacterial dysentery (arthritogenic bacteria) or other infxn |
| Seronegative Spondyloarthropathies: Enteropathic Arthritis - Reiter Syndrome | most HLA-B27 positive; Clinical Triad: Arthritis, Conjunctivitis, Urethritis |
| Rheumatic Fever: Pathophysiology | usu follows GAS infxn (S. pyogenes); commonly pharyngitis (less common S. cellulitis); formation of antibodies cross-reactive w/surface capsular antigens of S. pyogenes and self antigens on myosin and troponin |
| Rheumatic Fever: Clinical Synopsis | migratory large joing polyarthiculitis is mc presentation; Myocarditis/Valvulitis (CHF, pericarditis, valvulitis heart murmur); Subcut nodules (Aschoff Bodies - painless on extsor surfaces of wrists/elbows/knees; Chorea face/limbs dt basal ganglia |
| Rheumatic Fever: Clinical Course | spontaneous resolution in most pts; only a minority develop extra-articular dx dt antibody attachment to heart |
| Tuberculosis Arthritis: Pathophysiology | hematogenous spread to joints/bones; freq a/w tuberculous osteomyelitis in same location; may be a reactivation of latent infxn esp if immunocompromised; granulomatous inflamm of synovium |
| Tuberculous Arthritis: Clinical Synopsis and Course | most MONOarticular; fever; joint erythema/pain/swelling; dec ROM; pos PPD (purified protein derivative); tuberulosis of spine (Pott's Disease) can spread contiguously causing tuberculous meningitis/myelopathy; vertebral collapse (gibbis deformity and kyph |
| Septic Arthritis: route of infection | 1. direct inoculation (diagnostic, therapeutic or surgical); 2. localized spread (contiguous osteomyelitis or cellulitis); 3. hematogenous spread (sepsis) |
| Septic Arthritis: common pathogens | N. gonorrhea (mc in teens/adults); S. aureus (mc in kids); Pseudomonas (usu IVDA) |
| Septic Arthritis: Clinical Synopsis | presents w/joint pain, edema, erythema; may present during episode of sepsis; GC usu polyarticular (knees, hips); Non-GC is MONOarticular; articular cartialge damage; periarticular osteomyelitis |
| Lyme Arthritis: Route of Infection | tick bite; Borrelia burgdorferi spirochete; localized slow spreading skin rash (erythema migrans); systemic spread via blood/lymph (heart, CNS, muscles, joints); infectious arthritis is migratory/oligoarticular; chronic arthritis dt immune rxn not infxn |
| Viral Arthritis: pathophysiology | dt deposition of immune complexes in synovium rather than direct infxn of joint space (except Rubella that infects synovial cells) |
| Viral arthritis: clinical synopsis, course | may have Hx of recent viral immunization; polyarthritis; fever; viral exanthem; regional lymphadeonpathy; false positive RF is common; arthritis resolves w/resolution of viral infxn |
| Gout | metabolic; usu first metatarsalphalangeal joint (podagra severe pain in foot); |
| Gout: Pathophysilogy of Primary Gout | idiopathic (few inherited enzyme defect); elev serum uric acid dt disorder of purine metabo (over or underproduction of uric acid); hyperuricemia forms monosodium urate crystals in joint fluid; intense inflam rxn; usu MONOarthicular; Gouty Tophi deposits |
| Gout: Pathophysiology of Secondary Gout | primary disease process usu leads to overproduction of uric acid or blockage of its excretion; accounts for 10% of gouty arthritis; usu dt malignancy |
| Gout: General Pathology | deposition of monosodium urate crystals in joints, subcut tissues, and skin; in joints crystals are yellow-brown needle-shaped; in skin/subcut tissue precipitates form gray-white amorphous solid material called tophus (uratoma) |
| Pseudogout | usu MONOarticular, mc in knee; CCPD (rhomboidal) crystals in joint fluid; phagocytosis of crystals results in acute inflam rxn; synovial hyperplasia w/chronic inflam changes; acute onset of joint pain/swelling/erythema; dec ROM; NEVER polyarticular |
| Hemochromatosis-related Arthropathy: General Pathology | nml people maintain ~1-3g total iron; in these pts, body stores up to 20-40g; excess iron produces excess free radicals (hydroxyl, superoxide); extensive tissue damage via (DNA damage, impaired ptn synth, cell membrane integrity); inflam, fibrosis |
| Hemochromatosis-Related Arthropathy: clinical course | synovial iron deposition leads to arthritis usu in 2nd/3rd MP joints; opportunistic infxns dt inc availability of iron for microbe metabolism (Yersinia sp, Listeria monocytogenes, mucormycosis) |
| Amyloid Arthropathy: Pathophysiology | all forms of amyloidosis have unique ptn: Pentraxin (other parts vary the etiology and presentation); amyloid arthropathy is more common in Secondary Amyloidosis of Multiple Myeloma |
| Amyloid Arthropathy: Multiple Myeloma | amyloid composed of immunoglobulin light chain fragments |
| Amyloid Arthropathy: Primary Amyloidosis | amyloid composed of immunoglobulin light chain fragment |
| Amyloid Arthropathy: Chronic Hemodialysis | amyloid composed of beta-2-microglobulin |
| Amyloid Arthropathy: Pathology | amyloid is a homogenous,highly refractile substance w/affinity for congo red dye; deposition in synovium; POLYarthicular, usu symmetric, joint swelling/pain, red ROM |
| Degenerative Osteoarthritis | mc in hand (DIP), PIP; definate familial tendency dt polymorphisms in type 2 collagen; |
| Osteoarthritis: General Pathophysiology | dec aggrecm/proteoglycans (less pliable, loss of water/elasticity degenerates cartilage (axial compression: fragments, fissures, softening, erosion, ulceration); degeneration of subchondral bone (osteophytosis); chronic synovitis (IL-1/TNF/MMPs/radicals) |
| Osteoarthritis: Clinical Synopsis, Xray findings | chronic joint effusion/pain; dec ROM; may become acutely inflamed; Heberden's Nodes (DIP exostoses); dec joint space; degen of subchondral bone (eburnation, sclerosis, marginal osteophytosis - compensatory bone overgrowth to "stabilize" joint) |
| Hypertrophic Osteoarthropathy: Pathophysiology | a/w pulmonary dx; subperiosteal, cancellous and new bone forms along distal diaphysis of long bones; excessive CT/subperiosteal edema elevates periosteum; arthritis; clubbing of phalanges (perivasculitis, edema, fibrous tissue in nailbed) |
| Hypertrophic Osteoarthropathy: Clinical Triad | 1. clubbing of fingers and toes; 2. periosteal new bone form in diaphysis/metaphysis of long bones (slight enlargement of extremities); arthritis w/joint effusions |
| Neoplasms: Gaglion Cyst Pathology | usu dorsal or volar wrist; GCs are <2cm; herniated structure dt tearing in soft tissue over a tendon sheath/joint capsule; filled w/viscous clear or milky-white fluid; can form from excess mucoid fluid form in tendon sheath; "pseudocyst" b.c no epithelium |
| Neoplasms: Synovial Cyst Risk Factors | Rheumatoid arthritis (mc); seronegative spondyloarthropathies; OA, CPPD disease; medial knee (mc); dt herniation of joint capsule and synovium posteriorly in respone to chronic knee effusion (synovial lined cyst) |
| Pigmented Villonodular Synovitis: Pathology of Diffuse PVS | unknown; usu larger synovial joints; thickened synovium w/combo of villous and nodular prolif; benign (lipid-laden MQs, Hemosiderin-laden (pigmented) multinuclear giant cells, fibroblasts, MNCs); synovial hyperplasia involved epiphysis = subchondral cysts |
| Synovial Sarcoma: Pathology | usu knees; most arise near joint (few w/in joint); contiguous invasion of bone common; resembles developing synovium; does NOT arise from synovium (rather, pluripotnent mesenchyme); spindle and large epithelioid polygonal cells secreting hyaluronic acid |
| Synovial Sarcoma: Cytogenics/Clinical Course | >90% of tumors have t(X;18) translocation not associated w/other sarcomas (involves SYT gene on chrom 18q11 and SSX1 or SSX2 on XpII - transcription regulators); recurrence after resection common; metastases to lung/bones common even w/Rx |
| Spinal Muscular Atrophy: SMA Type I | ska: familial SMA/infantile MA/Werdnig-Hoffmann Dx; auto recessive; mutated SMN1 gene (survival motor neuron); may also have NAIP mutation (neuronal apoptosis inhibitory ptn); degen of spinal motor neurons from motor nuclei of CNV caudally |
| Spinal Muscular Atrophy: SMA Type I - Clinical Synopsis | onset early in infancy; dec fetal movement/postural tone/hypotonia (mc cause of "floppy babies"); progressive muscle weakness never able to sit or walk; bulbar dysfxn of brainstem = abnml breathing patterns; CK level normal; hypostatic pneumonia, 8% 10YS |
| Muscular Dystrophy: General Pathophysiology | dystrophin (component of cell membrane cytoskeleton in smooth/skeletal/cardiac muscle and brain); the dystrophin-glycoprotein complex connects inner cytoskeleton (F-acti) to basal lamina; dystrophin gene 2.5mil bp prone to mutation (Xp21) |
| Muscular Dystrophy: General Pathology | dystrophin malfxn predisposes skeletal muscle to rapid degen and rapid, ineffective regenerative response from skeletal myoblasts (mononuclear satellite cells); net effect is muscle cell necrosis a/w: inflam, myocyte phagocytosis, fibrosis |
| Muscle Dystrophy: General Clinical Synopsis | progressive muscle weakness (usu prox-to-distal); various amounts of pseudohypertrophy, esp in calves |
| Duchenne Muscular Dystrophy | non-fxnl dystrophin gene; 1/3500 male; usu X-linked; skeletal m necrosis a/w chronic inflam, fibrosis, contracture; usu dx when child sits/ambulates; prox-distal weakness; paradoxical m hypertrophy; MR; elevated CK; death 20-30yo cardio/pulm scoliosis |
| Becker Muscular Dystrophy | partial fxn of dystrophin gene; 1/30,000 males; usu X-linked; skeletal m necrosis, chronic inflam, fibrosis, contracture; dilated cardiomyopathy; symptoms not as obvious as Duchenne; elevated CPK levels; later onset and slower progression than Duchenne |
| Myotonic Dystrophy | mc adult muscular dystrophy; auto dom; abnml trinucleotide repeat expansion in DMPK gene on chrom 19q; "anticipation" inc severity in successive generations dt amplificationof repeats |
| Myotonic Dystrophy: Clinical Synopsis | onset as younger adult; progressive muscle weakness and wasting of some cranial innervated muscles and distal limbs; myotonia; cataracts; hypogonadism; cardiomyopathy; frontal balding |
| Myotonic Dystrophy: Variants - Congenital Myotonic Dystrophy | severe congenital form seen in the offspring of women w/the disease; much earlier onset and severity w/ greater anticipation of the trinucleotide repeat |
| Mitochondrial Myopathies: Pathophysiology | mitochondria function in OxPhos and produce ATP; mutations common (lack of introns, dec DNA repair); meiotic separation causes variable normal and mutant mtDNA; clinical manifestation depends on ratio; CNS/myocardium have low threshold for Sx to occur |
| Traumatic Compartment Syndrome: Pathophysiology | injury leads to edema in closed anatomical space; results in tissue pressure exceeding blood perfusion pressure and vascular compromise, muscle ischemia, and infarction |
| Compartment Syndrome: Clinical Synopsis | extremity fracture is most common initiating event (tibia or radius); inc pain of an unexpected severity |
| Myasthenia Gravis: Pathophysiology | derangement of immune b-cells; autoantibodies against ACh nicotinic postsynaptic receptors at neuromuscular jxn in skeletal muscle (smooth and cardiac muslce are not affected); early pattern of progressively reduced muscle strength w/repeated use |
| Myasthenia Gravis: Pathophysiology cont'd | recovery of muscle strength after period of rest (esp in extraocular and swallowing muscles); symptomology occurs only when number of ACh receptors <25% of nml; most pts have THYMUS dx too (hyperplasia 90% - remove it to dec # of autoantibodies) |
| Myasthenia Gravis: Clinical synopsis | commonly presents w/ocular muscle weakness (ophthalmoplegia, strabismus, ptosis); generalized muscular weakness that increases with exertion |
| Polymyositis/Dermatomyositis | in adults, strong association with presence of malignancy (aka: myositis w/cancer - lung, breast, ovarian, stomach) |
| Polymyositis/Dermatomyositis: Variant - Neoplasia related polymyositis/dermatomyositis | 1 in 5 pts have occult malignancy (lung, breast, ovary); unknown pathophysiology; usu takes several years for occult malignancy to manifest |
| Lambert-Eaton Myasthenic Syndrome: Synopsis | generalized neuromuscular transmission disorder; dt defect in ACh release; usu a/w small cell carcinoma of lung |
| Lambert-Eaton Myasthenic Syndrome: Pathophysiology | dt autoantibodies directed at voltage-gated Ca channels in presynaptic motor nerve terminal leading to channelopathy |
| Lambert-Eaton Myasthenic Syndrome: Clinical Synopsis | may or may not occur in pts w/associated malignancy; insidious onset and slow progression over wks; weakness in axial/girdle muscles sparing limbs; myalgias; autonomic disturbances (dry mouth, impotence common) |
| Myositis Ossificans Circumscripta | metabolic; aka: Rider's Bone; commonly dt traumatic injury; also dt ischemia; usu arm or thigh; localized deposition of Ca leading to ossification, localized tenderness esp w/movement; spontaneous resolution in most pts |
| Drug-related Myopathy: Corticosteroid Myopathy | aka: steroid myopathy; prolonged CCsteroid usage manifest mild-severe myopathic changes; more freq w/fluorinated steroids (dexamethasone or triamcinolone); inhibits ptn synth and inc ptn degradation; same changes as Cushings (1* hypercorisolism) |
| Drug-related myopathy: Chronic Corticosteroid Myopathy | insidious onset of proximal muscle weakness progresses to generalized weakness/atrophy (type2 fibers); NORMAL serum CK |
| Drug-related myopathy: Acute Corticosteroid Myopathy | very rare; acute onset of rhabdomyolysis dt SHORT-term high dose CCsteroids; ELEVATED serum CK; myoglobinuria common |
| Drug-related myopathy: Corticosteroid - Clinical course | slow resolution after decreasing/stopping CCsteroid use; some weakness is permanent; inc incidence of associated osteopenia |
| Serotonin Syndrome: Common causes | SSRIs (sertraline-Zoloft; fluoxetine-Prozac; paroxetine-Paxil; fluvoxamine-Luvox); Tricyclic antidepressants; MAO inhibitors; methamphetamines |
| Serotonin Syndrome: Pathophysiology; Clinical Synopsis | usu dt excessive SSRI use or combo of 2 SSRIs; caused by excessive serotonin activity in spinal cord and brain; rapid onset/progression; fever; altered sensorium (hallucinations); muscle rigidity and tremors |
| Neuroleptic Malignant Syndrome: Common Causes | Butyrophenones, Lithium, major Tranquilizers (Phenothiazines, heloperidol, Thioxanthines); Atypical Antipsychotics (clorazil); Reglan |
| Neuroleptic Malignant Syndrome: Pathophysiology | probably dt dec dopamine activity in CNS (blocked D2-receptors; dec dopamine levels); inhibition of transmission in nigrostriatum and hypothalamus = muscle rigidity/alt thermoreg; dysfxn of sympNS; similar to malignant hyperthemia & serotonin syndrome |
| Neuroleptic Malignant Syndrome: Clinical Synopsis | most pts develop NMS w/in 2wks of starting neuroleptic meds; fever, altered sensorium, muscle rigidity/tremors |
| Rhabdomyosarcoma | most common soft tissue carcinoma in children (originates from muscle cells high p53 mutation rate) |
| Fibromyalgia: Pathophysiology | primarily a disease of CNS; abnormality in central pain sensation processing w/in thalamus; NT abnormalities |
| Ehlers-Danlos Syndrome: Normal Physiology of CT | 28 genes contribute to collagen ptn structure (spread out over most chromosomes); 19 different types of collagen produced as long polymers that line up to form microfibrils; proteoglycans are core ptns bound to glycosaminoglycans (MPS) glue of CT matrix |
| Ehlers-Danlos Syndrome: General Pathophysiology | gen. CT abnormalities dt collagen defects in strength, elasticity, integrity, and healing properties of soft tissue or x-linking leading to: Skin hyperextensibility, Joint hypermobility, Soft tissue fragility, Poor wound healing/"cigarette paper" scars |
| Ehlers-Danlos Syndrome: Vascular Type (Type IV) Pathophysiology | type III collagen defect leading to total absence of type III collagen |
| Ehlers-Danlos Syndrome: Clinical Course/sequelae | pregnancy is very risky for Vascular Type EDS pts; they also have shortened life expectency dt aortic rupture or to bowel rupture |
| Pseudoxanthoma Elasticum: Pathophysiology | pts may secrete abnormal glycosaminoglycan that coats elastic fibers causing calcification and fragmentation of fibers |
| Pseudoxanthoma Elasticum: Pathology | elastic and collagen fiber fragmenetation a/w calcification |
| Pseudoxanthoma Elasticum: Clinical Synopsis | chilhood/teen onset; pseudoxanthomas (yellowish plaques) and subcut yellow orange-skin rash on lateral neck, antecubital and popliteal fossas; lax skin (cutis laxis); eyes: BLUE SCLERA, retinal angoid streaks (Ca in peripapillary retina) |
| Pseudoxanthoma Elasticum: Clinical Course/sequelae | inc incidence of premature atherosclerosis, mitral valve abnormalities, hypertension, acute GI bleeding (dt mucosal Ca deposition/ulceration); retinal hemorrhages leading to ambylopia |
| Cutis Laxa: General Pathology/Pathophysiology | alterations in quantity/morphology of elastin dt few elastic fibers or fiber fragmentation; abnml x-linking of elastin |
| Cutis Laxa: Clinical Synopsis | redundant, loose, sagging deep wrinkling of skin usu on face and neck; easy bruisability; poor wound healing |
| Cutis Laxa: Causes of Secondary (acquired) Cutis Laxa | inflammatory dermatitis (eczema), erythema multiforme |
| Cutis Laxa: Clinical Course/sequelae | inc incidence of: pulmonary emphysema, aortic aneurysm, bladder diverticula |
| Marfan Syndrome: Pathophysiology | usu aut dom; Fibrillin component of microfibrils accompanying elastin; FBN1 mutation results in defective fibrillin glycoprotein; the abnml allele disrupts microfibril formation dt Dominant Negative Effect |
| Marfan Syndrome: Clinical Synopsis | tall, long limbs (dolichostenomelia); ligament laxity/joint hypermobility w/subluxation and injury; medial necrosis of aorta (dilation and dissection); mitral valve sclerosis/prolapse; aortic valve sclerosis; pectus excavatum; scoliosis; ectopia lentis |
| Marfan Syndrome: Clinical Course/sequelae | inc incidence of: scoliosis, mitral valve sclerosis and prolapse, aortic valve regurgitation, aortic dissection/rupture leading to sudden death |
| Osteogenesis Imperfecta: Genetics | auto dom; mutation in any gene coding for COL1A1 or COL1A2 retards normal type I collagen (similar to thalassemias); heterogeneity leads to phenotypic heterogenicity |
| Osteogenesis Imperfecta: Pathology/Pathophysiology | Type I collagen predominantly found in bone and fibrous tissue; results in thin trabecular bone a/w thinning of cortex |
| Osteogenesis Imperfecta: Clinical Synopsis | all cases present at birth/infancy; multiple fx, easy bruising, abnml teeth (dentinogenesis imperfecta) |
| Osteogenesis Imperfecta: Type I | auto dom; defect in only 1 of the 2 genes; mild decrease in type I collagen; generalized osteoporosis, normal stature, no deformities, hearing loss, minimal propensity to fracture |
| Osteogenesis Imperfecta: DDx, Clinical course/sequelae | inflicted injury (child abuse); depends on clinical type; Types III and IV ahve reduced life expectancy dt inc incidence of respiratory infxn from insufficiency dt multiple rib fractures and progressive kyphoscoliosis |
| Dystrophic Calcinosis Cutis | acconts for 90% of all soft tissue calcifications dt trauma/scarification, cellulitis, skin neoplasia, systemic inflam (scleroderma); NORMAL serum Ca and phosphate; may progress to ossification (heterotropic bone formation) |
| Metastatic Calcinosis Cutis | dt: chronic renal failure, hyperparathyroidism, sarcoidosis, milk-alkali syndrome; ELEVATED serum Ca and phosphate; vascular calcif may cause ischemia/necrosis of skin or organ; finely speckled calcification throughout soft tissue |
| Iatrogenic Calcinosis Cutis | dt IV calcium or phosphate; surgical trauma; tumor lysis syndrome dt chemoRx |
| Idiopathic Calcinosis Cutis | localized to an area; no known cause |
| Dystrophic Calcinosus Cutis: Variants - Tumoral Calcinosis | familial predisposition; auto recessive; hip, elbow; few have renal insufficiency a/w hyperphosphatemia; progressively enlarging calcified nodules in juxta-articular location |
| Dystrophic Calcinosus Cutis: Variants - Transplant-associated Calcinosus Cutis | occurs in relation ot different types of whole organ transplants; unknown etiology; possibly dt infusion of blood products containing citrate and Ca that create a "calcification" environment |
| Bacterial Cellulitis: Immunocompetent | S. pyogenes (usu rapid onset); S. aureus |
| Bacterial Cellulitis: Immune deficient | Gram-negative rods (Pseudomonas); anaerobes, fungi (candida) |
| Bacterial Cellulitis: clinical course and sequelae | 5% mortality; few get sepsis; few get fatal exotoxinemia (TSS); Post-streptococcal glomerulonephritis can occur; Rheumatic fever can occur; metastatic seeding (endocarditis, meningitis, osteomyelitis, septic arthritis) |
| Systemic Sclerosis: Pathology | excessive collagen deposition in dermis (atrophy of skin appendages, vascular obliteration, mononuclear cells (Tcells) in dermis/dubcutis; eosinophils present; Also deposition in organs: Lungs, heart, bowel, kidneys, muscles, joints |
| Systemic Sclerosis: Clinical Synopsis | usu older adults; Raynaud phenomenon (spasm of distal aa in digits; pain/blanching); generalized weakness; arthralgia; areas of dermal sclerosis; sclerodactyly; dysphagia |
| Systemic Sclerosis: Clinical Course/sequelae | inc incidence of: diffuse pulmonary fibrosis, congestive heart failure, renal failure |
| Soft Tissue Sarcomas in Adults: pathogenesis | small percentage are radiation-induced (~300/yr); dt radiation for another neoplasm (breast/cervical/ovarian carcinomas) |
| Soft Tissue Sarcoma in Children: Rhabdomyosarcoma | most common soft tissue sarcoma in kids (>50%); In young child - orbital/paranasal sinus/genitourinary; In Teenager: Extremities; painless enlarging mass; 65% die w/in 5yrs |
| Soft Tissue Sarcoma in Kids: Synovial Sarcoma | second most common soft tissue sarcoma in kids; lower extremity (mc); upper extremitiy; minority metastasize to lung (hematogenous) |
| Xeroderma Pigmentosum: Pathophysiology | rapid aging of exposed skin dt inability to repair UV-induced DNA damage |
| Xeroderma Pigmentosum: Clinical Synospsis | child onset; many pigmented spots (like freckles); many actinic keratoses; photosensitivity w/severe sunburn in infancy; development of skin neoplasms as young child; inc incidence of cancers as child (basal, squamou cell carcinomas, malignant melanoma) |
| Ichthyosis: General Pathophysiology | genetic abnormality in maturation of keratinocytes |
| Ichthyosis Vulgaris (ichthyosis simplex, hyperkeratosis congenita) | 1 in 250; mc ichthyosis; auto dom; defective keratine that is difficult to desquamate leading to hyperkeratosis (thick epidermis); absence of granular layer of epidermis; childhood onset; gen scaling except flexural surfaces a/w atropy; improves as adult |
| Lamellar Ichthyosis (Ichthyosis congenita, Collodion Baby, Harlequin Fetus) | 1 in 300,000; mc auto rec; mutation in gene for keratinocyte transglutaminase (TGM1) on Chrom 14q; hyperkeratosis, prominant Granular layer in epidermis |
| Lamellar Ichthyosis: Clinical synopsis/course/sequelae | large coarse scales over most of body w/thickened palms and soles; ectropion present; inc incidence of dehydration and electrolyte imbalance, failure to thrive dt ptn loss, sepsis |
| Epidermolysis Bullosa Simplex | aka: EB Epidermal type; mc type; auto dom; mutation in keratin-5 gene (KRT5) on Chrom 12q or keratin-14 (KRT14) on 17q |
| EB Simplex: Pathology | blisters form by cytolysis w/in basa or spinous layers of epidermis; keratinocytes often have abnormalities in density and organization of keratin filaments; bullous separation w/in epidermis allows lesions to heal WITHOUT SCARS |
| EB Simplex: Clinical Stuff | common on feet after traumatic injury; not a/w organ abnormalities except the skin; |
| EB Simple: Variant Weber-Cockayne Syndrome | EB simplex confined to hands and feet |
| Allergic Contact Dermatitis | inflam of skin w/varying degrees of erythema, edema, and vesiculation dt delayed type hypersensitivity rxn |
| Allergic Contact Dermatitis: Pathophysiology | small chemical molecules responsible for ACD must bind to carrier ptns on Langerhans cells (situated w/in supreabasilar layer of epidermis...the APCs in skin that interact w/CD4 helper Tcells) |
| Allergic Contact Dermatitis: Common allergens | poison ivy, nickel, latex, formaldehyde, perfumes/cosmetics... |
| Allergic Contact Dermatitis: Contact Dermatitis Variant | inflammatory rxn that is NOT immune-mediated, but rather caused by a direct toxic effect on the skin (ex: gasoline, bleach, etc) |
| Urticaria: Pathophysiology | aka: hives; urticaria dt release of serotonin, histamine, bradykinin, kallikrein, or ACh; INTRADERMAL edema from capillary and venous vasodilation; mc mechanism is IgE contacting allergin causing histamine release from mast cells (or comp-med or drug-ind) |
| Urticaria: Hereditary Angioedema variant | auto dom; deficiency of C1-esterase for complement pathway (serum level dec); episodic nonpitting edema on extremities usu; (also intesting = abdominal pain or respiratory tract = fatal asphyxia) |
| Anaphylaxis: synospsis | immunopathologic systemic allergic rxn manifested by urticaria and/or angioedema w/hypotension or bronchospasm |
| Anaphylaxis: pathophysiology | inciting agent is exposure/ingestion to allergen; generates IgE antibody; upon re-exposure, allergen binds to fixed antigen-specific IgE leading to mast cell/basophil degranulation and release of histamine, leukotriene C4, prostaglandin D2, tryptase |
| Anaphylaxis: clinical synopsis | most severe rxns occur w/in minutes or hrs of exposure (parenteral exposure via stings, IV, etc are faster and more severe); delayed anaphylaxis can occur after days; inc capillary permeability leads to urticaria, angioedema, generalized edema (mc symptom |
| Anaphylaxis: clinical synopsis cont'd | inc bronchial smooth muscle tone leads to wheezing, airway obstruction and SOB; decreased vascular smooth muscle tone leads to systemic hypotension; increaased secretion from mucous membranes |
| Acute Eczematous Dermatitis: Genetics and Pathophysiology | most pts have positive family history of: asthma, allergic rhinitis, atopic dermatitis; probably dt disordered immune response in helper Tcell lymphocytes, esp an imbalance of cytokines |
| Acute Eczematous Dermatitis: Clinical Synopsis | intensely PRURITIC erythematous and scaling plaques; most manifest other atopic symptoms (bronchial asthma, recurrent/chronic urticaria, allergic rhinitis; Elevated circulating IgE |
| Psoriasis: Pathophysiology | unknown; markedly accelerated cell cycle for keratinocytes, resulting in overproduction and hyperadhesion which forms plaque; immune dysregulation of Tcells also present (hyperplasia of epidermis a/w intense CD4Tcell lymphocyte inflammation); +/-arthritis |
| Seborrheic Dermatitis: Pathophysiology | unknown; presence of Malassezia sp is probably a contributing factor; Tcell depression/dysfunction is present; activation of alternative complement pathway |
| Lichen Planus: Pathophysiology | caused by aberrant cell-mediated immune response including IgM deposition in epidermis (wickham striae) |
| Discoid Lupus Erythematosus: Pathophysiology | UV photodamage exposes/creates a heat shock ptn w/in keratinocytes that acts as antigen for Tcell-mediated epidermal cell cytotoxicity; deposition of immunoglobulin and/or complement at the dermal-epidermal junction in most cases |
| Morphea: Pathology | lymphoplasmacytic infiltrate a/w dermal edema in early inflam stage; late stage: excessive collagen deposition in dermis (atrophy of epidermal skin appendages, vascular obliteration, mononuclear cells (Tcells) in dermis/subcutis; eosinophils) |
| Pemphigus: Pathophysiology | bound and circulating complement-fixing IgG antibody directed against surface of keratinocytes; Pemphigus autoantibodies bind desomglein1 and 3 on keratinocyte (bind desomsomes and desomosome free areas); cause loss of cell-cell adhesion = ACANTHOLYSIS |
| Pemphigus: Clinical Synopsis | onset usu older adults; mc lesion is flaccid bulla on normal skin; few have oropharyngeal lesions; Nikolsky Sign = sliding of finger across skin produces blistering |
| Pemphigus: Clinical Course/sequelae | bullous formation in epidermis (no scarring); mortality rate ~10% dt complications from mucosal ulcerations and/or secondary bacterial infxn |
| Pemphigus: Paraneoplastic Pemphigus variant | develops in pts w/malignancies: mc: non-Hodgkin lymphoma; chronic lymphocytic leukemia; Waldenstrom macroglobulinemia; thymoma, bronchogenic squamous cell carcinoma |
| Pemphigus: Paraneoplastic Pemphigus variant - Pathophysiology | tumor antigens are thought to evoke immune response leading to development of x-reactive IgG autoantibodies; usu involves skin, respiratory tract and bowel; mortality rate usu 90% dt sepsis |
| Pemphigus: Benign Familial Pemphigus variant | aka: Hailey-Hailey Disease; auto dom w/incomplete penetrance; probable defect in keratinocyte adhesion secondary to primary Ca pump ptn defect (ATP2C1 on Chrom 3); onset in 2nd-4th decade intertriginous areas (axilla and inguinal); relapses/remissions |
| Bullous Pemphigoid: Pathophysiology | IgG autoantibodies directed against hemidesomsomal BP antigens BP230 (BPAg1) and BP180 (BPAg2 - type XVII collagen) leads to complement activation and chemotaxis of neutrophils/eosinophils followed by inflammatory injury |
| Dermatitis Herpetiformis: Pathophysiology | depositionof IgA at epidermo-dermal jxn or in basement membrane of a viscus leading to complement fixation and neutrophil chemotaxis forming a vesicle |
| Dermatitis Herpetiformis: Clinical Course | all pts have underlying symptomatic or asymptomatic gluten-sensitive enteropathy (celiac disease/celiac sprue); inc incidence of other autoimmune disorders and malignant lymphoma and primary gastrointestinal lymphoma |
| Erythema Multiforme: Pathophysiology | hypersensitivity rxn triggered by variety of stimuli; immune complex deposition variable; lymphocytic infiltrate at dermal-epidermal jxn around dermal vessels a/w keratinocyte necrosis and subepidermal bullae formation; Severe: epidermal/mucosal necrosis |
| Erythema Multiforme: clinical course/sequelae | Minor form: undergoes spontaneous resolution after lasting a few weeks; Major form: has 12% mortality rate d/t sepsis |
| Erythema Multiforme Variants: Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Complex | SJS <10% of body area; SJS/TEN Overlap 11-29% of body surface; TEN >30% of body surface |
| Erythema Multiforme Variants: Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis Complex - Pathophysiology | majority of cases a/w medication use (usu sulfonamides or anti-seizure meds); dermis and epidermis begin to accumulate activated Tcells and macrophages which release large amts of cytokines (TNF, IFN-g, IL-2); full thickness epidermal necrosis at D-E jxn |
| Erythema Nodosum: Pathophysiology | unknown; probably a hypersensitivity rxn dt infxn (Strep is mc), systemic inflam disese (inflam bowel, sarcoidosis), or medication use; |
| Acne Vulgaris: Pathophysiology | presence of Proprionibacterium acnes which metabolizes FAs in sebum; abnormal sloughing of epithelial cells that line sebaceous follicles of skin leading to chronic plugging of pores |
| Hidradenitis Supprativa: Pathophysiology | recurrent bacterial infxns of apocrine sweat glands |
| Hidradenitis Supprativa: Clinical synopsis/course/sequelae | onset at puberty, inc incidence w/autoimmune disease pts; recurrent inflam furuncles (nodules) and carbuncles; chronic/recurrent; fistulous tracts can occur; scarification common; inc incidence of lymphedema dt scars; slight inc in squamous cell carcinoma |
| Drug-Induced Bullous Disease | greatest incidence w/semisynthetic PCNs and Sulfamethoxazole/trimethoprim; dt immunologically mediated inflam response; primarily acitvation of drug-specific CD8Tcells; most resolve spontaneously upon discontinuance of drug; recurrance w/repeat exposure |
| Henoch-Schonlein Purpura: Pathophysiology | Type III immunopathologic disease (immune complex deposition); vasculitis dt deposition in small blood vessels or capillaries (IgA, activated C3) |
| Laceration: Pathophysiology | tissue bridging is present |
| Incised Wound: Pathophysiology | tissue bridging is NOT present |
| Animal Bite Wounds: common pathogens from dogs | Pasteurella sp; S. aureus; Anaerobes |
| Human Bite Wounds: | if distance btw canine is >2cm, then adult inflicted the wound; if <2cm child inflicted the wound |
| Human Papilloma Virus Infection: Pathophysiology | epitheliotropic virus infects squamous epithelial cells causing proliferation and formation of hyperkeratotic papule/WART; flat warts are minimally hyperkeratotic |
| Human Papilloma Virus Infection: Clinical course/sequelae | definitavely oncogenic; cervical cancer, squamous cell cancer of skin and mouth |
| Molluscum Contagiosum: Pathophysiology | viral infxn of squamous epidermal cells leads to proliferation; multiple pearly umbilicated vesicles usu less than 5mm; progressive spread dt autoinoculation; may give rise to large lesions in immunodeficience pts (HIV,etc) |
| Impetigo: Routes of Infection | contact w/either carriers of pathogen or people w/current impetigo infxns; autoinoculation from area carrying Strep (GAS; S. pyogenes) or S. aureus such as nose |
| Bullous Impetigo: Pathophysiology | almost always S. aureus; dt exotoxin that causes layers of epidermis to separate and form bullae |
| Impetigo: Clinical Course/sequelae | If S. pyogenes is the pathogen, then either of the following can rarely occur: 1. Post-strep glomerulonephritis; 2. Rheumatic Fever; If pt has repeated episodes, they are probably a chronic carrier of S. aureus and/or S. pyogenes in nasopharynx |
| Bacterial Cellulitis: common pathogens in immunocompetent | S. pyogenes (usu rapid onset); S. aureus |
| Bacterial Cellulitis: common pathogens in immunodeficient | Gram-negative rods (Pseudomonas), anaerobes, fungi (candida) |
| Bacterial Cellulitis: Clinical course/sequelae | mortality 5%; some develop sepesis or exotoxinemia (TSS, etc); Post-strep glomerulonephritis; Rheumatic fever; metastatic bacterial seeding in internal organs occurs regularly (endocarditis, meningitis, osteomyelitis, septic arthritis) |
| Erysipelas: common pathognes | usu caused by GAS beta-hemolytic (small minority dt S.pneumoniae and other strep sp); occurs on distal upper extremities (mc) or face |
| Erysipelas: Pathophysiology/clinical synopsis | a more superficial infxn of skin than cellulitis; fever, rapidly expanding areas of intense erythema, pain and induration w/sharply demarcated border; bullae possible |
| Necrotizing Cellulitis: common pathogens in immune competent | Exotoxin-producing S. pyogenes (aka: "Flesh-eating bacteria"), or S. aureus |
| Necrotizing cellulitis: Pathophysiology | tissue hypoxia favors facultative anaerobes; O2-dependent bactericidal killing mech (Myeloperoxidase-Halide) isn't fxnl; Gases (H2, N2, H2S, CH3) accumulate in soft tissues = crepitus/radiolucency; Combo of Coag/Liquif necrosis of soft tissue |
| Necrotizing cellulitis: Gas Gangrene Variant: Pathophysiology | either spores or live bacteria of C. perfringens enter deep soft tissue and multiply; EXOTOXINS and exoenzymes digest/necrotize tissue; Formation of Gas as metabolic byproduct |
| Meningococcemia (Neisseria Meningitidis): Risk Factors - Hereditary Complement Component Deficiency | deficiency of late component(s): C5, C6 C7, C8 and C9; almost all pts will develop at least one episode of meningococcemia during lifetime (usu CH50 as a screening tool) |
| Meningococcemia (Neisseria Meningitidis): Pathophysiology of Acute Meningococcemia | 1. Directly invades endothelial cells (vascular injury; endothelial necrosis, intraluminal thrombosis, perivascular dermal bleeds); 2. Systemic Inflammatory Response dt ENDOTOXIN release (low BP Shock; disseminated IV coag (DIC); ischemic organ failure) |
| Meningococcemia (Neisseria Meningitidis): Pathology of Acute Meningococcemia | acute vasculitis w/neutrophils and nuclear dust in/around vessels; hemorrhage in surrounding tissues (purpura/petechiae); Microthrombi in dermal vessels a/w neutrophil/platelets/fibrin; Meningococci (single or diplococci) in luminal thrombi/vessel walls |
| Gonococcemia: Pathophysiology | N. gonorrhea spread from primary site (ex: endocervix, urethra, pharynx, rectum) and disseminate via blood; skin lesions caused by direct invasion of endothelial cells leading to vasculitis/hemorrhagic skin lesions |
| Gonococcemia: Clinical Course/sequelae | commonly evoles to septic arthritis; osteomyelitis, meningitis, endocarditis, septic shock (disseminated intravascular coagulation (DIC) or Acute respiratory Distress Syndrome (ARDS) |
| Leprosy (aka: Hansen Dx): Tuberculoid Leprosy Pathophysiology | immue system reacts strongly to infxn; epitheliod granulomas and Langhans Giant Cells common; acid-fast bacilli are ABSENT |
| Leprosy (aka: Hansen Dx): Tuberculoid Leprosy Clinical Synopsis | skin lesions (begin as hypopigmented macule); evolve into sharply demarcated plaques; anesthesia in relation to skin lesion peripheral nerves; does not manifest dissemination; remains relatively STABLE |
| Leprosy (aka: Hansen Dx): Lepromatous Leprosy Pathophysiology | NO granulomatous inflammation; diffuse infiltrate of foamy MQs dt acid-fast bacilli growth; FEW/NO lymphocytes or Giant Cells; acid-fast bacilli invade peripheral nerves w/o immune system rxn allowing systemic dissemination |
| Leprosy (aka: Hansen Dx): Lepromatous Leprosy Clinical Synopsis | skin lesions begin as hypopigmented macule evole into demarcated red plaques; peripheral nerve-associated skin anesthesia; disseminated to internal organs (liver, bone, larynx); infectious form dt presence of acid-fast bacilli in lesions |
| Cutaneous Atypical Mycobacteria Infections: Clinical Synopsis | erythematous nodule on hand w/vesicles or shalow ulcer; few w/ascending lymphatic infxn and inflam nodules (psorotrichosis-like); Reactive lymphadenopathy common; PPD Mantoux test negative (PPT-B may be positive) |
| Bacillary Angiomatosis | dt Bartonella henselae or quintana; subcut nodules of prolif blood vessles a/w Gram-neg bacilliary bacteria; may form nodules in organs/skin; responds to antibiotics; can be disseminated/death for AIDS pts; lesions look like Kaposi Sarcoma (dx via biopsy) |
| Cutaneous Candidiasis | heat, moisture, chronic skin irritation promotes fungal growth; usu in intertriginous locations (Intertrigo) and perineum in kids (Diaper dermatitis) |
| Cutaneous Candidiasis: risk factors | obesity, diabetes mellitus (dt combo of acquired immune def and chronically elevated blood sugars provide good fungi environment); Antibiotic Rx (disrupts normal flora); Immune deficient state |
| Candidal Paronychia and Risk Factors | erythematous/edematous nail fold areas; freq develop secondary bacterial infxn; chronic immersion in water (dishwashers, bartenders, food handlers); Diabetes Mellitus; Immune deficient state; |
| Pityriasis/Tinea Versicolor | caused by Malassezia furfur which is normal skin flora; hypopigmented or hyperpigmented skin patches usu on trunk |
| Cutaneous Mycoses/Dermatophytes: Pathogenic Species | Trichophyton, Microsporum, Epidermophyton; dt direct contact from humans or animals; remain ocnfined to keratinous zone of skin; look at KOH skin scrapes for hyphae and w/calcofluor staining under scope |
| Lice: Pathophysiology | pierce superficial dermis w/mouthpats and feed off blood; saliva has anticoagulant properties; eggs laid by femaile are attached to hair shafts (called "nits"); hatchlings are called nymphs and also have piercing mouth parts to obtain host blood |
| Lice: Clinical Course and Sequelae | chronic infestation w/o Tx; outbreaks in families/schools; pubic lice considered STD; body lice vector for Bartonella quintana (causes infective endocarditis), epidemic typhus and trench fever; infectious agents altered by specific arthopod (flea vs tick) |
| Scabies: pathophysiology/course | Gell-Coombs type IV delayer hypersensitivity rxn to parasitic infestation accounts for symptoms; if immunocompetent usu self-limiting and scratches destroy eggs/mites; chronic if deficient (human mite worse than animal); 2* bacterial infxn common |
| Ticks: Clinical Course/sequelae | major vector disease transmission to humans; Lyme disease; Rocky mountain spotted fever,etc |
| Fleas: major vectors for transmission to humans | bubonic plague, typhus, parasitic tapeworms, etc |
| Prophyria on the Boards!!: General Pathophysiology | any enzyme defect in heme biosynthesis; elevated heme precursors (porphyrins, protoporphyrins, porphobilinogen); excessive porphyrin intermediates diffuse to skin and absorb UV/generate ROS and damage skin (face/hands/chest/shoulders); CNS/liver porphyria |
| Porphyria Cutanea Tarda (uroporphyrinogen decarboxylase deficiency) | most common porphyria; auto dom; homos - child onset; hets - may be delayed/asymptomatic; elevated intermediates = severe dermal photosensitiviy (vesicle/bullae/erosions/scars/alopecia); facial melasma; dark urine; intermeds = liver injury/adenocarcinoma |
| Porphyria Lab Diagnosis | quantitative urinary porphilogen, Free erythrocyte protoporphyrin, Total plasma porphyrins, Total urine porphyrins, Total erythrocyte porphyrins (difficult), Fractionated urinary/plasma porphyrins by HPLC |
| Vitiligo: Pathophysiology | epidermal melanocytes are completely lost leading to depigmented areas; melanocyte destruction is autoimmune mediated |
| Xanthoma: Pathophysiology | composed of foamy (lipid-laden) macrophages; usu but not always a/w systemic hyperlipidemia |
| Stasis Dermatitis: pathophysiology | poor venous circulation leads to blood pooling in lower legs; venous hypertension; localized hypoxia/vessel damage; hemorrhage; long-term low grade fever |
| Stasis Dermatitis: Clinical stuff | edema, venous vericosities, diffuse red-brown discoloration representing deep dermal deposits of HEMOSIDERIN (from extravasated RBCs) and skin hyperpigmentation; skin ulcers; chronic and progressive |
| Seborrheic Keratoses: sign of lesser-Trelat variant | multiple eruptive (appearing over short period of time) seborrheic keratoses a/w and internal malignancy; usu GI adenocarcinoma |
| Melanocytic Nevus: Pathophysiology | benign prolif of melanocytes forming "nests" w/in skin; may or may not develop dark terminal hairs (hairy nevus); onset as child w/more appearing into adulthood later to regress/disappear |
| Melanocytic Nevus: Giant Congenital Melanocytic nevi Variant | high risk w/time for malignant transformation to melanoma |
| Melanocytic Nevus: Atypical Nevus Syndrome Variant | aka: dysplastic nevus syndrome, familial atypical multiple mole and melanoma syndrome (FAMMM) |
| Melanocytic Nevus: Atypical Nevus Syndrome Variant - Clinical synpsis | multiple melanocytic nevi manifest histologic dysplasia; strong family Hx; very high risk of transformation into melanoma |
| Dysplastic Nevus: Clinical Synopsis | onset usu in childhood (can develop as adult); >0.5cm; irregular borders/surface/pigmentation; numerous dysplastic nevi = higher risk of melanoma esp w/fam hx |
| Actinic Keratosis | face/neck/sun-exposed areas; neoplastic transformation of epidermal keratinocytes into carcinoma; usu <1cm, flat erythematous keratotic lesion (verrucous); 5% transform to invasive Squamous Cell Carcinoma (SCC) |
| Basal Cell Carcinoma | face/neck/sun-exposed areas; dt pluripotential cells w/in basal layer of epidermis or hair follicles; proliferation of basaloid cells (basalioma) in nests and nodules; very slow growing; metastasis does occur but is vanishingly rare |
| Nevoid Basal Cell Carcinoma Syndrome | predisposition to cancer in general; esp cutaneous basal cell carcinoma |
| Keratocanthoma | solitary, 1-2cm; rapid growth over wks; skin-colored/reddish papule progresses to dome-shaped nodule w/central crater-ulceration w/keratin plug-like horn; most spontaneously resolve; few evolve into invasive SCC; few recur after surgical excision |
| Cutaneous Squamous Cell Carcinoma | face/neck/sun-exposed areas; from epidermal cells usu from precancerous actinic keratoses lesions ; erythematous plaque evolves into nodule <1.5cm ulcer; few cutSSC are metastatic at time of diagosis (SCC on lips/ears have highest metastasis rate) |
| Cutaneous Squamous Cell Carcinoma: Variants - HPV related SCC | usu on penis, labia, or peri-anal region |
| Cutaneous Squamous Cell Carcinoma - Marjolin Ulcer | ulcerative SCC that arises in area of chronic inflammation, such as osteomyelitis |
| Malignant Melanoma: Risk Factors | chronic sun exposure (esp child/teen); fair skin; positive family Hx for melanoma; multiple atypical or congenital nevi |
| Microstaging (histologic) of Malignant Melanoma: Clark's Classifications | determined by anatomic level of invasion |
| Microstaging (histologic) of Malignant Melanoma: Clark's Classifications: Level I | confined to epidermis (mc) |
| Microstaging (histologic) of Malignant Melanoma: Clark's Classifications: Level II | invasion into superficial papillary dermis |
| Microstaging (histologic) of Malignant Melanoma: Clark's Classifications: Level III | invasion into deep papillary dermis |
| Microstaging (histologic) of Malignant Melanoma: Clark's Classifications: Level IV | invasion into reticular dermis (lower dermis) |
| Microstaging (histologic) of Malignant Melanoma: Clark's Classifications: V | invasion into subcutis |
| Clark's Level III or less: | does NOT require regional surgical dissection of lymph nodes |
| Breslow's Classification | determined by vertical thickness in millimeters; slowly replacing Clark's system |
| Malignant Melanoma: Biological Behavior | most melanomas grow radially (lentiginous) for months-yrs followed by an invasive vertical (nodular) growth w/high probability of metastasis; metastasis during radial growth is rare; |
| American Joint Committee on Cancer TNM Clinical Staging Systems | (T= tumor size; N = number of lymph nodes involved; M = presence of distant metastasis); staging of lesion predicts prognosis; includes combo of histo eval of excised neoplasm coupled w/results of radiographic studies and regional surgical dissection |
| Malignant Melanoma: Clinical Synopsis | may be de novo or from existing nevus; variability/changes in coloration; inc in size; irregular/asymm borders; presence of satellite lesions; itching; erosion/ulceration |
| Malignant Melanoma: Clinical course/sequelae | the > thickness/local depth > chance of LN/systemic metastases = worse prognosis; Clark's II or < is curable; Breslow's 1mm or <is curable; recurrance rate for cutaneous melanoma is 30%; 20% metastasis at Dx (35% 5YS); relapse risk dec w/time |
| Superficial Spreading Melanoma | most malignant melanoma cases; upper back in men/legs in women; macular lesion w/asymm borders and variable pigment w/pink halo; |
| Primary Nodular Melanoma | 2nd most common type of melanoma; 18% of cases; de novo w/rapid vertical growth w/o initial radial growth phase of superficial spreading melanomas; trunk/head/neck; highly aggressive and early metastasis |
| Cutaneous Tcell Lymphoma | malignant lymphoma dt clonal expansion of CD4 helper memory Tcells that also manifest the cutaneous lymphocyte antigen (CLA); common immunophenotype; common Tcell gene rearrangement; malignant Tcells are dermatotropic/reenter circuation via lymphatics |
| Langerhans Cell Histiocytosis: pathophysiology | widespread infiltration of tissues by Langerhans cell histiocytes admixes w/EOSINOPHHILS from tissue destruction; probably an immunopathological rxn; NOT CLONAL; NOT A NEOPLASM |
| Kaposi's Sarcoma | elderly Medit/East Europe (slow); HIV-related (fast)occurs at any age; cytokines synergistic w/HIV tat gene product to induce neoplastic prolif of endothelial cells; Human Herpesvirus Type 8 aids in neoplastic transformation (ORKF12 oncogene); skin/URT/GI |
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