1. Breast Pathology

2. Lymphatic drainage Anatomy of Breast

3. Extension of metastasis:
Cervical,
Supraclavicular,
Groin
Lymphnodes

4. Clinical Clues to Early Detection
Lump 70%
Self detection 90%
Pain/nipple discharge/ erosion/retraction/
enlargement/ itchy nipple/
red hard breast/ axillary mass
Back/bone pain/ jaundice/ weight loss
Upper and Outer Quadrant lump

5. Right breast mass with "peau d'orange" skin retraction, muscle retraction, and non tender axillary lymphadenopathy
44 yr old WF with a 1½ year history of right breast mass and pain, refused hospitalization for a probable carcinoma of the right breast when seen by her doctor six months prior to admission.
Four weeks prior to admission, the patient developed nausea, vomiting, coughing, shortness of breath, fatigue and increasing weakness.

6. Early disease:
Palpable mass
Breast pain
Nipple discharge
Ulceration
Skin- Dimpling / Edema/ Erythema
Axillary mass
Scaling of the nipple (Paget's disease)
Advanced disease:
Fixation of the mass to the chest wall
Axillary lymphadenopathy
Edema of the arm
Breast enlargement
Ulceration
Supraclavicular lymphadenopathy
Back pain
Bone pain
Jaundice
Weight loss

7. Paget’s Disease

8. Paget’sDisease of the Nipple: Manifests as an eczematous or psoriaform plaque. It is a skin manifestation of an underlying ductal adenocarcinoma of the breast.

9. A 48-year-old woman had experienced a prolonged history of chronic eczematous dermatitis of the nipple and areolar area for several years.
The lesion did not respond to topical treatment, and it progressively distorted the nipple with expansion into the surrounding skin.
Note a markedly scaly, crusted, and deformed nipple with a thickened, irregularly outlined adjacent nipple-areola complex.
An excisional biopsy confirmed the diagnosis of mammary Paget disease.
The patient developed an infiltrating ductal carcinoma of the underlying breast tissue with axillary lymph metastasis.
She was treated by mastectomy and radiation. No metastatic tumor was noted in the axillary lymph node.
She was alive and well
3 years after treatment.

10. Infiltrating Duct Carcinoma
The specimen consists of the skin of the breast (black arrows) with underlying breast tissue.
The blue arrows point to a poorly circumscribed yellow white mass which is the neoplasm.

11. Breast Cancer Incidnce:192,000/yr 10% hereditary Risk>-3-7 times
BRCA1 either inherited or somatically mutated with loss of heterozygosity may remove suppression of cell growth by gene product

12. The BRCA1 and BRCA2 (or Breast Cancer 1 and 2) genes
Responsible for all cases of familial ovarian cancer and approximately half of all cases of familial breast cancer.
Carrier of the BRCA1 and BRAC-2 Gene have a 15-45% chance of developing ovarian cancer compared to a 1.5% risk for non-carriers.
BRAC1-2 is associated with early onset breast cancer.
increase the risk of a second cancer. A woman with the mutation has an increased risk of ovarian cancer following breast cancer.
The BRCA1 and BRCA2 (or Breast Cancer 1 and 2) genes are felt to be responsible for nearly all cases of familial ovarian cancer and approximately half of all cases of familial breast cancer.
A woman that has been identified as being a carrier of the BRCA1 and BRAC-2 Gene have a 15-45% chance of developing ovarian cancer compared to a 1.5% risk for non-carriers. BRAC1-2 is associated with early onset breast cancer.
BRCA1 and BRCA2 mutations increase the risk of a second cancer. A woman with the mutation has an increased risk of ovarian cancer following breast cancer.

13. Red flags for hereditary cancers include:
A diagnosis of cancer at an early age.
Several family members with cancer.
Relatives with more than one type of cancer.
A history of bilateral cancer. This means cancer in both eyes or both breasts.
A history of multiple primary cancers in one person where one cancer was cured and another was diagnosed in later life.
Rare or unusual cancers such as male breast cancer
Ashkenazi or eastern European ancestry - these groups have been found to be at a higher risk for certain genetic mutations.

14. Cause for Concern:
Any woman family member has had both breast and ovarian cancer.
More than 3 women from the same side of the family have had breast or ovarian cancer.
Any woman family member has had breast or ovarian cancer before the age of 50.
Any man in the family has had breast cancer.

15. inherited BRCA2 mutation?
Both men and women who inherit a BRCA2 mutation have an increased chance for developing breast cancer.
Women who have an altered BRCA2 gene appear to have a similar risk of developing breast cancer compared with women with BRCA1 mutations.
The risk for ovarian cancer is also increased. Studies suggest that the ovarian cancer risk is between 16 and 27 percent.

16. ?Heredity- BrCa – 10% of all, & 40% under 30 are gene related
BRCA 1 on chr.17 (85% risk for BrCa & 50% for OvCa); also colon & prostate Ca
BRCA2 in M- male BrCa and melanomas
Identical twin sibling at risk for same Cancer

17. Epidemiology Affects 1 of 9 women in the U.S.
Increases with increasing age
More frequent in women of low parity with first child after 30
Increased in obesity
Increased in women with history of atypical hyperplasia
Increased in women with history of breast carcinoma
Increased in women with mother or sibling with breast cancer
Increased in women with mutations in BRCA1 or BRCA2 genes

18. Clinical Nature
Neoplasm spreads to regional (axillary) lymph nodes and then to distant sites including lungs, liver, and bones
Treatment and prognosis dependent on tumor size and presence of metastatic disease in lymph nodes or distant sites (stage) and estrogen and progesterone receptor status
Therapy includes local treatment (surgery and/or radiation treatment of the breast) and systemic therapy if warranted with either anti-estrogens (if the neoplasm is receptor positive) or chemotherapy

19. ? Male Breast Cancer
High prevalence in certain parts of Africa, a higher incidence of estrogen receptor positivity and more aggressive clinical behavior.*
Estimated new cases and deaths from breast cancer in the United States; American Cancer Society.: Cancer Facts and Figures 2008.
New cases:
182,460 (female)
1,990 (male)
Deaths: 40,480 (female)
450 (male) *Eur J Cancer Aug;34(9):

20. Male Breast Facts
Men with a BRCA2 mutation have a 6 percent lifetime risk of breast cancer — about 100 times more than other men's risk.
Inherited mutations in the cell-cycle checkpoint kinase 2 (CHEK-2) gene and the p53 gene
Radiation exposure
Klinefelters Syndrome (XXY syndrome)
30% cases have excess of HER2 (human epidermal growth factor receptor-2) protein expression

21. Reduced Androgen Activity
Exposure to estrogen.
Liver disease.
Excess weight. Obesity may be a risk factor for breast cancer in men, because it increases the number of fat cells in the body. Fat cells convert androgens into estrogen, increasing the amount of estrogen in your body and, therefore, your risk of breast cancer.
Excessive use of alcohol

22. FIBROCYSTIC BREAST DISEASE
Fibrocystic breast “condition” or fibrocystic breast “change.”
Estrogen-dependent, most commonly in women (still producing estrogen).
Changes are probably variants of normal: gross and microscopic cysts, papillomatosis, adenosis, fibrosis, and ductal hyperplasia.

23. Fibroadenoma/ Fibrocystic Disease
The pale grey cut surfaces show a bulging glistening appearance due to the predominant loose fibrous stroma rich in mucopolysaccharides. Note well defined outline
Benign cysts filled by serous fluid often have this blue color when viewed from the outside.

24. FIBROCYSTIC BREAST DISEASE
SIGNS / SYMPTOMS
Pain, tenderness, palpable masses, usually multiple and bilateral, worse or sometimes only present during the luteal phase.
Fluctuation in size of the cysts.
“Suspicious” masses should be biopsied.
Aspiration of a dominant cyst and / or Bx and /or MMG should be considered to assist in the Dx, although a MMG negative for malignancy does not R/O malignancy- only Bx rules out malignancy.

25. FIBROCYSTIC BREAST DISEASE
TREATMENT
Hormonal therapy theoretically the ticket, but not practical long term due to side-effects, risks, etc, although these rules can be bent for patients at the extreme end of the symptomatic spectrum.
Avoidance of caffeine, Vitamin E 440 IU/d.

26. NIPPLE DISCHARGE In the non-lactating female, the top 3 causes are:
1) Duct ectasia.
2) Intraductal papilloma.
3) Carcinoma.

27. NIPPLE DISCHARGE Evaluate:
1) The nature of the discharge- serous, bloody, purulent, milky.
2) Associated w/ a mass?
3) Unilateral or bilateral.
4) Single or multiple duct discharge.
5) Expressed or spontaneous.
6) Single site, or multiple sites.
7) Relation to menses.
8) Premenopausal or postmenopausal.
9) On estrogen or OCPs?

28. NIPPLE DISCHARGE
“A 40 year old female comes in with a 2 month history of a spontaneous bloody discharge from her right breast. On exam you are able to express blood with pressure in the upper outer quadrant of the breast. There is no palpable mass. Your DDx would include…….”

29. NIPPLE DISCHARGE GALACTORRHEA
The discharge of milk from the non-lactating breast.
Caused by hyperprolactinemia- can be due to: prolactin-producing adenoma of the pituitary, hypothyroidism, anti-psychotic medication, and other screwy things- see pg 1113.
A serum prolactin should be done. If elevated, a cause should be sought.

30. NIPPLE DISCHARGE EVALUATION
All patients should have a history and PE looking for the 9 things listed.
When localization is not possible, there is no palpable mass, the discharge is not bloody, and the MMG is normal, the patient should be followed every 3 months for a year, w/ a repeat MMG in 6-12 months if the discharge persists.

31. NIPPLE DISCHARGE EVALUATION
ALL PATIENTS W/ A UNILATERAL, BLOODY DISCHARGE SHOULD HAVE AT LEAST AN EXAM AND A MAMMOGRAM. CONSIDER REFERRAL FOR EXCISION OF THE INVOLVED DUCT.
ALL PATIENTS WITH A NEW MASS SHOULD HAVE A BIOPSY OF SOME SORT. NOT A MAMMOGRAM. A BIOPSY. REGARDLESS OF AGE.

32. BREAST CANCER Stats. Risk factors. Association w/ other malignancies.
ERT.
Genetic mutations- BrCa1, BrCa2, p53 gene.
Imaging, biopsy.

33. BREAST CANCER
“Most women w/ breast cancer have no identifiable risk factor.”
“There is no history of breast cancer among female relatives in over 75% of patients.”
1-2% of patients w/ a prior Dx of breast cancer will develop a second primary in the other breast.

34. BREAST CANCER
ALL PATIENTS WITH A NEW MASS SHOULD HAVE A BIOPSY OF SOME SORT. NOT A MAMMOGRAM. A BIOPSY. REGARDLESS OF AGE. REGARDLESS OF WHAT THE MAMMOGRAM SAYS.
A MMG NEGATIVE FOR MALIGNANCY DOES NOT R/O MALIGNANCY- ONLY BX RULES OUT MALIGNANCY

35. RANDOM CLINICAL PEARLS
BREAST CANCER
RANDOM CLINICAL PEARLS
60% of breast cancers develop in the upper-outer quadrant.
SYMPTOMS-
1) A painless lump is the presenting symptom in 70% of patients w/ breast cancer.
2) Less often: discharge, pain, skin retraction, itching of the nipple, redness, generalized hardness.

36. RANDOM CLINICAL PEARLS
BREAST CANCER
RANDOM CLINICAL PEARLS
PHYSICAL FINDINGS- hard, non-tender mass, fixed, poorly delineated margins. Skin or nipple retraction.

37. BREAST CANCER SCREENING
1)Self-breast exams for those interested in it at any age, those after age 50, and those at increased risk of breast cancer.
2)ALSO: yearly exams by a clinician and annual mammograms every 1-2 years after age 40, and yearly after age 50.
3)A breast cancer can be detected on MMG 2 years before they can be palpated.

38. WHEN TO ORDER A MAMMOGRAM
1) FOR SCREENING.
2) TO EVALUATE EACH BREAST AFTER THE Dx OF BREAST CANCER.
3) TO EVALUATE A BREAST MASS OR OTHER ABNORMALITY.
4) TO LOOK FOR A PRIMARY WHEN A METASTASIS OF ADENOCARCINOMA IS FOUND.
5) TO SCREEN PRIOR TO BIOPSY OR COSMETIC PROCEDURES.
6) FOLLOW-UP AFTER BREAST-CONSERVING SURGERY AND RADIATION.

39. DISORDERS DUE TO PHYSICAL AGENTS

40. HYPOTHERMIA, HEAT DISORDERS.
BURNS.
ELECTRIC SHOCK.
IONIZING RADIATION.

41. Hypothermia: Cold exposure
Skin temp <25°C
At 15°C skin looks pink –leads to tissue ischemia
At -4°C to -10° C frostbite (ice crystals inside tissues) occurs-neuropathic damage occurs
Keep warm/ keep dry/ keep moving
Avoid tobacco and alcohol

42. Hypothermia: Cold exposure
Superficial frostbit (frostnip) steady pressure with warm hand / Do not rub!
Deep frostbite – rapid warming immediately if safe
If danger refreeze exists do not thaw
Immerse the part in moving water bath at 40-42°C (Dry heat not recommended)

43. Heat Disorders
Heat syncope- a hypovolemia syndrome. BP <100. Usually vigorous exercise in the preceding 2 hrs precipitates the event. Cool moist skin and weak pulse.
Heat cramps- lasts 1-3 minutes. Due to sodium loss by sweat. Cool oist skin/ tender muscle. BP OK. Serum sodium low.
Keep him cool. Give saline solution

44. Heat Disorders
Heat Exhaustion- prolonged vigorous exercise with inadequate salt and fluid intake. High rectal temperature (>37.8°C) rapid pulse (> )
Exhibit nausea/ vomiting/ myalgia/ thirst/headache/ fatigue/ hysteria/ psychosis. Can progress to heat stroke.
Keep cool. Hydrate 1-2L in 2 hrs/salt/ fans/ice pack

45. Heat Disorders
Heat Stroke: Life threatening. Rectal temperature >41°C. Cerebral dysfunction/ impaired consciousness/ high fever/ Absence of sweating
At risk- very young and very old
Patients on medications- anticholinergis/antihistamines
Can be seen in marathon runners
High mortality-collapse/convulsions/coma
Reduce core temperature rapidly- ice water immersion/ evaporative cooling

46. Alpha radiation consists of helium-4 nucleus and is readily stopped by a sheet of paper.
Beta radiation, consisting of electrons, is halted by an aluminium plate.
Gamma radiation is eventually absorbed as it penetrates a dense material. Lead is good at absorbing gamma radiation, due to its density

48. Radiation Effects
Skin-Mucus membrane- redness/ loss of hair/ exfoliation/ thermal burns
BMD/ Pericarditis
Pneumonitis
Oropharyngeal ulcers
Hepatitis/ nephritis
Gonads
Radiation sickness: nausea/ anorexia/ exhaustion
Therapy- Serial lymphocyte counts/ chelation for radioisotopes

49. Classification OF BURNS
Only second- and third-degree burns are included in calculating the total burn surface area, since first-degree burns usually do not represent significant injury

50. First-degree burns affect only the outer layer of the skin
First-degree burns affect only the outer layer of the skin. They cause pain, redness, and swelling.
Second-degree (partial thickness) burns affect both the outer and underlying layer of skin. They cause pain, redness, swelling, and blistering.
Third-degree (full thickness) burns extend into deeper tissues. They cause white or blackened, charred skin that may be numb.

51. Electrical injuries - uncommon occurrence
resultant deaths occur per year
Factors- the voltage, current strength, resistance to flow, duration of contact, pathway of flow, and type of current.
Ohm's law: ‘voltage is equal to current times resistance’
high voltage above V
household appliances work at 110 V
Current is the volume of electron flow –DC or AC
Frequency 60 Hz
Resistance-impedance to electron flow and usually depends on the water content of a conducting material
low-voltage electrical injury

52. Respiratory muscle paralysis occurs at 20-50 mA.
Ventricular fibrillation may develop at mA and
Asystole, at currents greater than 2 A.
Flash burns- an electrical arc does not enter the body but just causes a severe thermal injury and singe nearby hairs
Ventricular fibrillation is more common with low-voltage AC; Delayed arrhythmias can occur up to 12 hours

53. Low-voltage burns
Thermal burns caused by prolonged contact; usually at least several seconds of contact are required.
They almost exclusively occur in the hands of adults and in the mouths of children. Children may chew on extension cords and receive an oral burn

54. About TASER! Deliver sequential DC pulses, up to 50,000 V
Deaths from TASER use have been reported
A superficial puncture wound
The most serious complications are from trauma subsequent to the shock.

55. Lightning A type of high-voltage DC electrical injury
Mild-superficial burns with associated loss of consciousness, amnesia, confusion, and tingling
Moderate injuries-may include seizures, respiratory arrest, and cardiac stunning
Severe lightning injuries-cause cardiopulmonary arrest, with a very low survival rate.

56. INFECTIOUS DISEASES

57. NOSOCOMIAL INFECTION
“Those not present or incubating at the time of hospital admission and developing hours after admission.”
5% of hospitalized patients develop one.
Carry a 5% mortality rate.
Most common are urinary tract infections.
Catheters of all types are associated w/ increased risk of an infection.
Are more often multiple drug resistant.

58. NOSOCOMIAL INFECTION
When looking at cultures, distinguish between colonization and infection.
PREVENTION- the most effective method of preventing nosocomial infections is handwashing.
Hand disinfectants.
Change central catheters every 3-4 days.
Attention to all catheters as a possible source of fever / infection.

59. INFECTIONS IN DRUG USERS
1) SKIN INFECTIONS- Staph aureus, oral flora (Strep, Pepto-sctreptococci), gram negatives, depending on injection site, practices etc.
2) HEPATITIS- B,C, AND D, ALSO A. can have multiple episodes w/ different agents
3) ASPIRATION PNEUMONIA-
4) TB-
5) PULMONARY SEPTIC EMBOLI- from venous thrombi or right-sided endocarditis.

60. INFECTIONS IN DRUG USERS
6) STDs-
7) AIDS-HIV
8) INFECTIVE ENDOCARDITIS-
9) VASCULAR INFECTIONS- septic thrombophlebitis, mycotic aneurysms.
10) OSTEOMYELITIS AND SEPTIC ARTHRITIS-

61. INFECTIONS IN DRUG USERS
TREATMENT
Work-up, cultures etc followed by broad-spectrum antibiotics effective against resistant Staph and others, nafcillin or vancomycin combined with gentamicin, depending on CXR, while awaiting culture results.

62. ACUTE INFECTIOUS DIARRHEA
1INFLAMMATORY
Presence of an invasive pathogen, parasite, or a toxin.
Colon commonly affected: frequent, bloody, small-volume stools, often fever, cramps, tenesmus, urgency.
The Bugs: Shigella, Salmonella, Campylobacter, Yersinia, invasive E coli, Entamoeba histolytica, Clostridium dificile (esp in the recently-hospitalized) .
Test for fecal leucocytes is positive.
Stool culture identifies the bug.
NON-INFLAMMATORY
Milder, small bowel disease.
Usually viral
stools are larger volume, non-bloody, watery, w/ nausea, vomiting, cramps, usually no fever.
The Bugs: Viruses: Norwalk virus, enteric adenoviruses, astrovirus, coronavirus; Vibriones: Vibrio cholera, Vibrio parahemolyticus

63. ACUTE INFECTIOUS DIARRHEA
NON-INFLAMMATORY
Bugs (cont)- enterotoxin-producing E coli, Giardia lamblia, cryptosporidium, agents causing food-borne gastroenetritis (Staph aureus, Bacillus cereus, Clostridium perfringens).
TREATMENT
Fluid replacement, electrolytes.
Most acute diarrheas resolve within 3-4 days.
Those that do not, or those that appear inflammatory, stool cultures should be done.

64. ACUTE INFECTIOUS DIARRHEA
TREATMENT
Therapy if cultures are positive for: Shigella, E coli 0157:H7, and Campylobacter.
For the rest, antibiotic treatment has not been shown to alter the natural history of the disease, and in fact may prolong the carriage of the bug and lead to relapse/recurrence.
Giardiasis treated with metronidazole (Flagyl)
Routine use of antibiotics is discouraged due to the emergence of resistant organisms.

65. ACUTE INFECTIOUS DIARRHEA
TREATMENT
TREAT THOSE:
1) WITH INVASIVE DISEASE.
2) WITH SYMPTOMS BEYOND 4 DAYS.
3) WITH > 8-10 STOOLS PER DAY.
4) WHO ARE IMMUNOCOMPROMISED.
Use anti-spasmodics (Immodium etc) only in those without invasive/inflammatory disease (fever, bloody stools).

66. TRAVELER’S DIARRHEA 80% are bacterial.
The Bugs: enterotoxigenic E coli, Campylobacter, Shigella, less frequently Aeromonas, Salmonella, Entamoeba histolytica, Giardia lamblia. Viruses: adenoviruses, rotaviruses.
Occurring within 1 week of travel, usually benign and self-limiting, resolves within 1-5 days.
Frequent, loose BM’s, watery, non-bloody, cramps, N/V, no fever

67. TRAVELER’S DIARRHEA
If stools are bloody, or fever is present → stool cultures and treatment.
Empiric treatment w/ Cipro 500 mg bid for 3-5 days, other fluoroquinolones, trim-sulfa.
Specific treatment may change w/ culture results, but often not.
See text re prophylaxis.

68. HIV INFECTION

69. Post Exposure: Early Symptoms
Flu-like illness within a month or two after exposure to the virus. This illness may include
Fever
Headache
Tiredness
Enlarged lymph nodes

70. Later Symptoms Asymptomatic 10-15 years
During the asymptomatic period, the virus is actively multiplying
Results in a decline in the number of CD4 positive T (CD4+) cells

71. Late Symptoms (?AIDS)
The first signs of infection are large lymph nodes, or swollen glands that may be enlarged for more than 3 months.
Other symptoms often experienced months to years before the onset of AIDS include:
Lack of energy
Weight loss
Frequent fevers and sweats
Persistent or frequent yeast infections (oral or vaginal)
Persistent skin rashes or flaky skin
Pelvic inflammatory disease in women that does not respond to treatment
Short-term memory loss
Frequent and severe herpes infections that cause mouth, genital, or anal sores, or shingles

72. “Opportunistic infections” = AIDS
Coughing and shortness of breath
Seizures and lack of coordination
Difficult or painful swallowing
Mental symptoms such as confusion and forgetfulness
Severe and persistent diarrhea
Fever
Vision loss
Nausea, abdominal cramps, and vomiting
Weight loss and extreme fatigue
Severe headaches
Coma

73. CD4+ (Helper) T cell Counts
Normal >
Risk increases for counts <400
AIDS if <200
Diagnosis – ‘HIV positive’- carrier of the disease
ELISA screen usually positive 1-3 months after exposure (up to 6 months)
Likely to develop antibodies to the virus-within 6 weeks to 12 months
Western blot technique required to confirm ELISA test

74. ?THERAPY No Cure! reverse transcriptase (RT) inhibitors
(Nucleoside/nucleotide inhibitors)
protease inhibitors, interrupt the virus from making copies of itself at a later step in its life cycle
fusion inhibitors - Fuzeon (enfuvirtide or T-20)
highly active antiretroviral therapy, or HAART

75. ?Side Effects Bone marrow depression Pancreatitis/ Polyneuritis
GI and Respiratory symptoms
Other severe reactions, including death

76. Therapy for opportunistic infections
Foscarnet and ganciclovir to treat CMV (cytomegalovirus) eye infections
Fluconazole to treat yeast and other fungal infections
TMP/SMX (Bactrim® or Septra®) (trimethoprim/sulfamethoxazole) or pentamidine to treat PCP (Pneumocystis carinii pneumonia)
Cancer therapy for NHL/ Kaposi’s Sarcoma

77. LYME DISEASE
Lyme borreliosis, caused by Borrelia burgdorferi, a spirochete.
The vector is the ixodid tick, of which there are 4 genomic groups.
Mostly seen in the northeast, north central, and mid-Atlantic states.
Accuracy of diagnosis is suspect, as patients are diagnosed with Lyme disease in areas where there is no known host/cycle for B burgdorferi.
Concerns about over diagnosis. See text.

78. LYME DISEASE CLINICAL 3 STAGES 1) STAGE 1- EARLY LOCALIZED INFECTION.
2) STAGE 2- EARLY DISSEMINATED INFECTION.
3) STAGE 3- LATE PERSISTENT INFECTION.

79. LYME DISEASE CLINICAL STAGE 1 - EARLY LOCALIZED INFECTION
ERYTHEMA MIGRANS.
1 week-10 days after the tick bite, at the site of the tick bite
Flat, slightly raised lesion, seen in areas of tight clothing- groin, axillae, thigh.
Classic description is the “Bull’s Eye” lesion, but a more heterogenous lesion is common.
50% have a flu-like illness.
Resolves w/ out treatment in 3-4 weeks.

80. 56,300 people were newly infected with HIV in 2006  (the most recent year that data are available).
Over half (53%) of these new infections occurred in gay and bisexual men.
Black/African American men and women were also strongly affected and were estimated to have an incidence rate than was 7 times as high as the incidence rate among whites.

81. LYME DISEASE CLINICAL STAGE 1 - EARLY LOCALIZED INFECTION
Atypical lesions or lesions that go unnoticed lead to misdiagnosis.
Asymptomatic cases not common- 7% incidence of asymptomatic seroconversion.

82. LYME DISEASE CLINICAL STAGE 2 - EARLY DISSEMINATED INFECTION
Hematogenous or lymphatic spread.
Wide variety of symptoms.
Days to weeks after the tick bite.
SKIN- secondary lesions not in the area of the tick bite, similar to the lesions in stage 1 but smaller.
CNS- headache, stiff neck.
MUSCULOSKELETAL- migratory pains in joints, muscles, tendons.
Fatigue and malaise.

83. LYME DISEASE CLINICAL STAGE 2 - EARLY DISSEMINATED INFECTION
Neurologic & musculoskeletal symptoms last hours to weeks, fatigue is persistent.
See text for what happens next- the organism sequesters itself in certain areas and produces focal symptoms: cardiac, neurologic, encephalitis, etc.

84. LYME DISEASE CLINICAL STAGE 3 – LATE PERSISTENT INFECTION
Months to years after initial infection.
Possibly an immunologic event rather than persistent infection – see pg 1490.
Again: Skin, Neurologic, and Musculoskeletal.
MUSCULOSKELETAL-
Up to 60%. Sxs are highly variable.
Arthritis, joint pain w/out objective findings, chronic synovitis.

85. LYME DISEASE CLINICAL STAGE 3 – LATE PERSISTENT INFECTION
NERVOUS SYSTEM
Both peripheral and central.
“Subacute encephalopathy”- memory loss, mood swings, sleep disturbance.
Axonal polyneuropathy.

86. LYME DISEASE CLINICAL STAGE 3 – LATE PERSISTENT INFECTION SKIN
ACRODERMATITIS CHRONICUM ATROPHICANS
Can occur up to 10 years later.
Not common in the U.S., mostly in Europe due to a different species of B burgdorferi.

87. LYME DISEASE CLINICAL Dx based on both clinical and lab findings.
Dx CRITERIA: Exposure to a “potential tick habitat” within 30 days prior to developing erythema migrans WITH:
1) Erythema migrans Dx’d by a physician, OR
2) One late manifestation, AND
3) Laboratory confirmation.

88. LYME DISEASE CLINICAL LAB
See text for details of the assay, the ELISA, western blot, etc.
Detect antibodies to B. burgdorferi.
See text for Dx criteria by the American College of Physicians. True positives vs. false positives. Read this. Really.
“Patients w/ non-specific symptoms without objective signs of Lyme disease should not have serologic testing done.” In this setting, false positives occur more commonly than true positives.

89. LYME DISEASE TREATMENT
Tetracycline, ampicillin, ceftriaxone, azithromycin, cefuroxime, imipenem.
A Dx of Erythema migrans by a physician warrants immediate treatment w/ no other diagnostic tests.
Treatment dependent on clinical manifestations, see table 34-4 pg 1492.
Again see pg 1493 for precaution about Dx (and, thus, treatment) being a clinical one w/ CONFIRMATION by serologic tests, and that the serologic tests are fraught w/ difficulty.
Beware of the patient presenting demanding treatment for his/her Lyme disease.

90. LYME DISEASE TREATMENT Oral therapy for most cases, weeks usually.
IV therapy for patients with neurologic / CNS manifestations.
Most patients will have prompt resolution of symptoms within 4 weeks of completing therapy.
“True treatment failures are uncommon.”
See pg 1493 re patients treated for Lyme Disease who have persistent symptoms, and how continuing to treat them, at least for Lyme Disease, is not productive
Life long immunity is not complete, pts are subject to re-infection.

91. 1) SYSTEMIC COMPLAINTS-
CLINICAL FINDINGS
1) SYSTEMIC COMPLAINTS-
Fever, night sweats, weight loss, even in the absence of an infection, but a work-up is in order for the patient w/ fever.
2) SINOPULMONARY DISEASE-
PNEUMOCYSTIS JIROVECI (yee row vet zee)- the “new”, though not yet universally accepted, name of Pneumocystis carinii, and its pneumonia is the most common opportunistic infection associated w/ AIDS. Formerly called PCP pneumonia.

92. 2) SINOPULMONARY DISEASE-
CLINICAL FINDINGS
2) SINOPULMONARY DISEASE-
Sxs of PCP can be vague, findings non-specific.
Dx is made based on CXR sputum cultures.
Most cases of PCP occur at CD4 counts below 200, at which point prophylaxis is given the uninfected patient.
TB- as well as atypical Mycobacteria such as Mycobacterium avium.
COMMUNITY-ACQUIRED PNEUMONIA- the most common cause of pulmonary disease in HIV.

93. 2) SINOPULMONARY DISEASE-
CLINICAL FINDINGS
2) SINOPULMONARY DISEASE-
SINUSITIS- tends to be chronic.
NONINFECTIOUS PULMONARY DISEASE- Kaposi’s sarcoma, non-Hodgkin’s lymphoma.
3) CNS DISEASE
TOXOPLASMOSIS.
LYMPHOMA.
AIDS DEMENTIA.
CRYPTOCOCCAL MENINGITIS- w/ Cryptococcus neoformans.

94. 4) PERIPHERAL NERVOUS SYSTEM
CLINICAL FINDINGS
3) CNS DISEASE
HIV MYELOPATHY.
PROGRESSIVE MULTIFOCAL LEOKOENCEPHALOPATHY (PML).
4) PERIPHERAL NERVOUS SYSTEM
INFLAMMATORY POLYNEUROPATHIES.
SENSORY NEUROPATHY.
MONONEUROPATHIES.
Treatment aimed at symptomatic relief- Neurontin (gabapentin).

95. CLINICAL FINDINGS 5) RHEUMATOLOGIC ARTHRITIS.
OTHER RHEUMATOLOGIC SYNDROMES- lupus, Reiter’s syndrome, psoriatic arthritis.
6) MYOPATHY
Proximal muscle weakness.
Need to distinguish it from the myopathy as a side effect of zidovudine therapy.

96. CLINICAL FINDINGS 7) RETINITIS
CMV- most common retinal infection in HIV.
8) ORAL LESIONS
ORAL CANDIDIASIS.
HAIRY LEUKOPLAKIA- caused by EBV.
ANGULAR CHELITIS.
APHTHOUS ULCERS.
9) GASTROINTESTINAL
ESOPHAGEAL CANDIDIASIS-

97. CLINICAL FINDINGS 9) GASTROINTESTINAL
HEPATIC DISEASE- various infections, and progression from the chronic carrier state of hepatitis B and C to cirrhosis, liver failure, and carcinoma.
BILIARY DISEASE- cholecystitis, sclerosing cholangitis.
ENTEROCOLITIS- COMMON. Bacteria: Campylobacter, Salmonella, Shigella. Viruses: CMV, adenoviruses. Protozoans: Cryptosporidium,Giardia, Entamoeba histolytica, Isospora.

98. CLINICAL FINDINGS 9) GASTROINTESTINAL
ENTEROCOLITIS- symptomati patients should have stool culture, O&P. If negative, colonoscopy, Bx. If all negative presumptive Dx of AIDS Enteropathy.
GASTROPATHY- inadequate acid production → increased susceptibility to Campylobacter, Salmonella, Shigella, poor absorption of drugs.
MALABSORPTION- idiopathic vs infection with Cryptosporidium, Mycobacterium avium.

99. CLINICAL FINDINGS 10) ENDOCRINE HYPOGONADISM.
ADRENAL INVOLVEMENT AND HYPOFUNCTION.
THYROID DYSFUNCTION.
11) SKIN MANIFESTATIONS
HERPES SIMPLEX.
HERPES ZOSTER.
MOLLUSCUM CONTAGIOSUM.
FOLLICULITIS, FURUNCULOSIS, IMPETIGO

100. CLINICAL FINDINGS 12) HIV-RELATED MALIGNANCIES
ANAL DYSPLASIA AND SQUAMOUS CELL CARCINOMA- from HPV.
CERVICAL DYSPLASIA AND CARCINOMA- from HPV.
13) GYNECOLOGIC MANIFESTATIONS
VAGINAL CANDIDIASIS.
CERVICAL DYSPLASIA AND NEOPLASIA.
PID.

101. 14) INFLAMMATORY REACTIONS
CLINICAL FINDINGS
14) INFLAMMATORY REACTIONS
IMMUNE RECONSTITUTION SYNDROMES OR “IRIS.”- as the immune system improves and CD4 count rises with initiation of antiretroviral therapy.

102. RISK TO HEALTHCARE PROFESSIONALS
Risk of HIV transmission from a single needle stick from an HIV-infected patient is about 1:300.
Risk is higher w/: deep puncture, large inoculum, high viral load.
Risk from mucous membrane exposure is too low to quantitate.
Follow universal precautions, no recapping, etc.

103. RISK TO HEALTHCARE PROFESSIONALS
NEEDLE STICK CONSELING, PROPHYLAXIS
After a needle-stick, counseling, HIV testing, baseline, retested at 6 weeks, 3 months, 6 months.
POST-EXPOSURE PROPHYLAXIS
Treatment w/ zidovudine reduces seroconversion by 79%.
Providers should be offered some form of post-exposure prophylaxis.

104. RISK TO HEALTHCARE PROFESSIONALS
POST-EXPOSURE PROPHYLAXIS
Therapy modified in the face of source-patient who has a high viral load, drug resistance.
Prophylaxis should begin ASAP, continued for 4 weeks.
Not 100% effective at reducing seroconversion.
“Safe sex” talk also needs to happen.

105. RISK TO HEALTHCARE PROFESSIONALS
POST-EXPOSURE PROPHYLAXIS AFTER SEXUAL AND DRUG USE EXPOSURE
Hard data does not exist, but there are similarities between the immune response following transcutaneous and mucosal exposure.
Regimen similar to that for needle sticks in healthcare workers.
Not recommended after 72 hours.

106. RISK TO HEALTHCARE PROFESSIONALS
POST-EXPOSURE PROPHYLAXIS AFTER SEXUAL AND DRUG USE EXPOSURE
Should occur w/ appropriate counseling re how to prevent further exposure- clean needles, “safe” sex, etc.

107. PROGNOSIS Improving. 1995- 50,610 deaths. 1999- 16,273 deaths.
The ticket is access to healthcare and appropriate antiretroviral therapy w/ ability to monitor CD4 counts, viral loads, to tailor therapy to each patient, including appropriate prophylaxis etc.

108. PREVENTION OF PERINATAL TRANSMISSION
In the absence of prophylaxis, between 13% and 40% of infants born to HIV+ women become infected.
Risk is higher w/ vaginal birth, high viral loads.
Also transmitted via breast milk- HIV+ women should NOT breast feed.
PREVENTION
Treatment antepartum, intrapartum, and postpartum reduces transmission by as much as 2/3.

109. Antimycotics Affecting Membrane Structure/Function
Ketoconazole (nizoral®)/ Itraconazole (sporanox®) / Fluconazole (diflucan®)(safest) (imidazoles):
cryptococcus, blastomycosis, candida species, dermatophytes
Amphotericin-B: toxic but useful for systemic fungal infections

110. Other Antifungal Agents
Terbinafine:
( lamisil®)
Dermatophytes, nail infections (onychomycosis)
Blocks ergosterol synthesis
GI upset/Headaches
Nystatin: (mycostatin®)
Local application to skin, mucus membranes
Candida species,- oral and vaginal thrush, intertrigo
AZOLES- clotrimazole, (lotrimin®), miconazole, (micatin®)
Vulvovaginal candidiasis
Dermatophytes,
Tinea: corporis/ pedis/ cruris
Seborrheic dermatitis
Pityriasis versicolor

111. 5-Flucytosine (ancobon®)
• analog of endogenous nucleotide
• competitively inhibits RNA synthesis
• mammalian cells unable to convert parent drug to metabolites
- bone marrow toxicity - anemia, leukopenia
• resistance due to altered metabolism of 5-flucytosine can emerge rapidly; use combination therapy
Cryptococcal meningits

112. HAART facts:
• In patients that fail to take the three drugs for a week, there is a rise in viral load.
• Non-compliance
• The HAART is very expensive, for example the combination of
zidovudine/lamivudine/protease inhibitor costs
$20,000 (US) per year
• A very effective combination therapy for HIV consists of-
zidovudine (AZT), lamivudine (3TC) and protease inhibitor (Indinavir)
•A major problem with these complicated drug regimens is compliance!
Partly related to drug side/toxic effects
• Non-compliance with protease inhibitor therapy is of serious concern as the new virus that emerges can be resistant to the inhibitor being taken and also resistant to other protease inhibitors. This is a major problem since the new resistant mutants may be transmitted to others

113. Anti-Hepatitis Agents
Hepatitis B-
Lamivudine-
cytosine analog (97% suppression in 2 weeks) recurs in 80% after ceasing therapy
Adefovir-
nucleoside analog
Interferon alfa-2b- loss of HBeAg 30% improvement
Hepatitis C-genotype 2,3
Interferon alfa-2b-
15-30% response (on no therapy) / 98% clearance on therapy
Peg* interferon alfa-2a
Peg interferon alfa-2b- increased ½ life,
less frequent dosing;
not superior to IF-alfa2b
*Peg= Poly Ethylene Glycol

114. Ribavarin (Virazole®)
Guanosine analog
Effective against influenza A, B, resp. syncytial virus, HCV, HIV-1
Avialable anti flu therapy: neuraminidase inhibitors
TamifluⓇ:(Osletamivir)
RelenzaⓇ: (Zanamivir)
?Flu vaccines-
Trivalent inactivated vaccine (TIV)
Live attenuated influenza virus (LAIV)

116. Antimycobacterial Drugs
• tuberculosis (Mycobacteria)
Overview
• among the leading causes of death from infectious disease (primarily tuberculosis)
• infections are among the most difficult to cure
Special Characteristics of Mycobacteria
• slow growth rate
- relatively resistant to antibiotics that depend on a rapid rate of division
- dormancy is possible (long-term treatment; months-years)

117. At risk group for Tb Older individuals Immune suppressed group- HIV/
Steroid & Immunosuprressant drug users
Diabetics
Alcoholics
Diagnostic tool: Manotux (tuberculin) skin test
Clinical features-
Weight loss
Night fever and sweats
Dry hacking cough
Hemoptysis
Lymphadenopathy
Tubercular meningitis

118. Standard therapy: Isoniazid Rifampin Pyrazinamide Ethambutol
All 4 Drugs for first 2 months
Drugs 1&2 only for next 4 months
Drug side effects-
Hepatitis
Neuritis
Optic neuritis/ color blindness