1 Breast Pathology. 2 Lymphatic drainage Anatomy of Breast.

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BreastBreastPathologyPathology

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Lymphatic drainage Anatomy of Breast

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Extension of metastasis:Extension of metastasis: Cervical, Cervical, Supraclavicular, Supraclavicular, GroinGroin

LymphnodesLymphnodes

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Clinical Clues to Early Detection

Lump 70%Lump 70% Self detection 90%Self detection 90% Pain/nipple discharge/ erosion/retraction/ Pain/nipple discharge/ erosion/retraction/

enlargement/ itchy nipple/ enlargement/ itchy nipple/ red hard breast/ axillary massred hard breast/ axillary mass

Back/bone pain/ jaundice/ weight lossBack/bone pain/ jaundice/ weight loss Upper and Outer Quadrant lumpUpper and Outer Quadrant lump

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Right breast mass with Right breast mass with "peau d'orange" "peau d'orange" skin retraction, skin retraction, muscle retraction, and muscle retraction, and non tender axillary non tender axillary lymphadenopathylymphadenopathy

44 yr old WF with a 144 yr old WF with a 1½ ½ year history of right breast mass and year history of right breast mass and pain, refused hospitalization for a probable carcinoma of the pain, refused hospitalization for a probable carcinoma of the right breast when seen by her doctor six months prior to right breast when seen by her doctor six months prior to admission. admission.

Four weeks prior to admission, the patient developed nausea, Four weeks prior to admission, the patient developed nausea, vomiting, coughing, shortness of breath, fatigue and increasing vomiting, coughing, shortness of breath, fatigue and increasing weakness. weakness.

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Early disease: Early disease: 1.1. Palpable mass Palpable mass 2.2. Breast pain Breast pain 3.3. Nipple discharge Nipple discharge 4.4. Ulceration Ulceration 5.5. Skin- Dimpling / Edema/ Skin- Dimpling / Edema/

Erythema Erythema 6.6. Axillary mass Axillary mass 7.7. Scaling of the nipple Scaling of the nipple

(Paget's disease)(Paget's disease)

Advanced disease: Advanced disease: 1.1. Fixation of the mass to the chest Fixation of the mass to the chest

wall wall 2.2. Axillary lymphadenopathy Axillary lymphadenopathy 3.3. Edema of the arm Edema of the arm 4.4. Breast enlargement Breast enlargement 5.5. Ulceration Ulceration 6.6. Supraclavicular lymphadenopathy Supraclavicular lymphadenopathy 7.7. Back pain Back pain 8.8. Bone pain Bone pain 9.9. JaundiceJaundice10.10. Weight loss Weight loss

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Paget’s Disease

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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.

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A 48-year-old woman had experienced a prolonged history of A 48-year-old woman had experienced a prolonged history of chronic eczematous dermatitis of the nipple and areolar area for chronic eczematous dermatitis of the nipple and areolar area for several years. several years.

The lesion did not respond to topical treatment, and it progressively The lesion did not respond to topical treatment, and it progressively distorted the nipple with expansion into the surrounding skin. distorted the nipple with expansion into the surrounding skin.

Note a markedly scaly, crusted, and deformed nipple with a Note a markedly scaly, crusted, and deformed nipple with a thickened, irregularly outlined adjacent nipple-areola complex. thickened, irregularly outlined adjacent nipple-areola complex.

An excisional biopsy confirmed the diagnosis of mammary Paget An excisional biopsy confirmed the diagnosis of mammary Paget disease.disease.

The patient developed an infiltrating ductal carcinoma of the The patient developed an infiltrating ductal carcinoma of the underlying breast tissue with axillary lymph metastasis. underlying breast tissue with axillary lymph metastasis.

She was treated by mastectomy and radiation. No metastatic tumor She was treated by mastectomy and radiation. No metastatic tumor was noted in the axillary lymph node. was noted in the axillary lymph node.

She was alive and well She was alive and well 3 years after treatment. 3 years after treatment.

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Infiltrating Duct Carcinoma

The specimen consists of the skin of the breast (black arrows) with underlying The specimen consists of the skin of the breast (black arrows) with underlying breast tissue. breast tissue.

The blue arrows point to a poorly circumscribed yellow white mass which is the The blue arrows point to a poorly circumscribed yellow white mass which is the neoplasm. neoplasm.

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Breast Cancer

Incidnce:192,000/yrIncidnce:192,000/yr 10% hereditary10% hereditary Risk>-3-7 timesRisk>-3-7 times BRCA1 either inherited or somatically mutated with loss of BRCA1 either inherited or somatically mutated with loss of

heterozygosity may remove suppression of cell growth by heterozygosity may remove suppression of cell growth by gene product gene product

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The BRCA1 and BRCA2 (or Breast Cancer 1 and 2) genes Responsible for all cases of familial ovarian cancer and Responsible for all cases of familial ovarian cancer and

approximately half of all cases of familial breast cancer. approximately half of all cases of familial breast cancer. Carrier of the BRCA1 and BRAC-2 Gene have a 15-45% chance of 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-developing ovarian cancer compared to a 1.5% risk for non-carriers.carriers.

BRAC1-2 is associated with early onset breast cancer. BRAC1-2 is associated with early onset breast cancer. increase the risk of a second cancer. A woman with the mutation increase the risk of a second cancer. A woman with the mutation

has an increased risk of ovarian cancer following breast cancer. has an increased risk of ovarian cancer following breast cancer.

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Red flags for hereditary cancers include:

A diagnosis of cancer at an early age. A diagnosis of cancer at an early age. Several family members with cancer. Several family members with cancer. Relatives with more than one type of 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 bilateral cancer. This means cancer in both eyes or both breasts. A history of multiple primary cancers in one person where one cancer was A history of multiple primary cancers in one person where one cancer was

cured and another was diagnosed in later life. cured and another was diagnosed in later life. Rare or unusual cancers such as male breast cancer Rare or unusual cancers such as male breast cancer Ashkenazi or eastern European ancestry - these groups have been found to be Ashkenazi or eastern European ancestry - these groups have been found to be

at a higher risk for certain genetic mutations. at a higher risk for certain genetic mutations.

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Cause for Concern: Any woman family member has had both breast and ovarian Any woman family member has had both breast and ovarian

cancer. cancer. More than 3 women from the same side of the family have had More than 3 women from the same side of the family have had

breast or ovarian cancer. breast or ovarian cancer. Any woman family member has had breast or ovarian cancer Any woman family member has had breast or ovarian cancer

before the age of 50. before the age of 50. Any man in the family has had breast cancer. Any man in the family has had breast cancer.

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inherited BRCA2 mutation? Both men and women who inherit a Both men and women who inherit a BRCA2BRCA2 mutation have an mutation have an

increased chance for developing breast cancer. increased chance for developing breast cancer. Women who have an altered Women who have an altered BRCA2BRCA2 gene appear to have a similar gene appear to have a similar

risk of developing breast cancer compared with women with risk of developing breast cancer compared with women with BRCA1BRCA1 mutations. mutations.

The risk for ovarian cancer is also increased. Studies suggest that the The risk for ovarian cancer is also increased. Studies suggest that the ovarian cancer risk is between 16 and 27 percent.ovarian cancer risk is between 16 and 27 percent.

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?Heredity- BrCa – 10% of all, & 40% under 30 are gene ?Heredity- BrCa – 10% of all, & 40% under 30 are gene relatedrelated

BRCA 1 on chr.17 (85% risk for BrCa & 50% for OvCa); also BRCA 1 on chr.17 (85% risk for BrCa & 50% for OvCa); also colon & prostate Cacolon & prostate Ca

BRCA2 in M- male BrCa and melanomasBRCA2 in M- male BrCa and melanomas Identical twin sibling at risk for same CancerIdentical twin sibling at risk for same Cancer

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Epidemiology

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

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Clinical Nature

Neoplasm spreads to regional (axillary) lymph nodes and then to distant Neoplasm spreads to regional (axillary) lymph nodes and then to distant sites including lungs, liver, and bones sites including lungs, liver, and bones

Treatment and prognosis dependent on tumor size and presence of Treatment and prognosis dependent on tumor size and presence of metastatic disease in lymph nodes or distant sites (stage) and estrogen metastatic disease in lymph nodes or distant sites (stage) and estrogen and progesterone receptor status and progesterone receptor status

Therapy includes local treatment (surgery and/or radiation treatment of Therapy includes local treatment (surgery and/or radiation treatment of the breast) and systemic therapy if warranted with either anti-estrogens the breast) and systemic therapy if warranted with either anti-estrogens (if the neoplasm is receptor positive) or chemotherapy (if the neoplasm is receptor positive) or chemotherapy

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? Male Breast Cancer

High prevalence in certain parts of Africa, a higher incidence of estrogen receptor High prevalence in certain parts of Africa, a higher incidence of estrogen receptor positivity and more aggressive clinical behavior.* positivity and more aggressive clinical behavior.*

Estimated new cases and deaths from breast cancer in the United States; Estimated new cases and deaths from breast cancer in the United States; American Cancer Society.: Cancer Facts and Figures 2008. American Cancer Society.: Cancer Facts and Figures 2008.

New cases: New cases: 182,460 (female)182,460 (female)1,990 (male)1,990 (male)

Deaths: 40,480 (female)Deaths: 40,480 (female) 450 (male)450 (male)

*Eur J Cancer. 1998 Aug;34(9):1341-7. *Eur J Cancer. 1998 Aug;34(9):1341-7.

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Male Breast Facts

Men with a BRCA2 mutation have a 6 percent lifetime risk of breast Men with a BRCA2 mutation have a 6 percent lifetime risk of breast cancer — about 100 times more than other men's risk. cancer — about 100 times more than other men's risk.

Inherited mutations in the cell-cycle checkpoint kinase 2 (CHEK-2) gene Inherited mutations in the cell-cycle checkpoint kinase 2 (CHEK-2) gene and the p53 geneand the p53 gene

Radiation exposureRadiation exposure Klinefelters Syndrome (XXY syndrome)Klinefelters Syndrome (XXY syndrome) 30% cases have excess of HER2 (human epidermal growth factor receptor-30% cases have excess of HER2 (human epidermal growth factor receptor-

2) protein expression2) protein expression

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Reduced Androgen Activity Exposure to estrogen. Exposure to estrogen. Liver disease. Liver disease. Excess weight. Obesity may be a risk factor for breast cancer in men, 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 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 androgens into estrogen, increasing the amount of estrogen in your body and, therefore, your risk of breast cancer. and, therefore, your risk of breast cancer.

Excessive use of alcohol Excessive use of alcohol

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FIBROCYSTIC BREAST DISEASE

Fibrocystic breast “condition” or fibrocystic breast “change.”Fibrocystic breast “condition” or fibrocystic breast “change.” Estrogen-dependent, most commonly in women 30-50 (still producing Estrogen-dependent, most commonly in women 30-50 (still producing

estrogen).estrogen). Changes are probably variants of normal: gross and microscopic cysts, Changes are probably variants of normal: gross and microscopic cysts,

papillomatosis, adenosis, fibrosis, and ductal hyperplasia.papillomatosis, adenosis, fibrosis, and ductal hyperplasia.

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Fibroadenoma/ Fibrocystic Disease The pale grey cut surfaces show a The pale grey cut surfaces show a

bulging glistening appearance bulging glistening appearance due to the predominant loose due to the predominant loose fibrous stroma rich in fibrous stroma rich in mucopolysaccharides. Note well mucopolysaccharides. Note well defined outline defined outline

Benign cysts filled by serous fluid Benign cysts filled by serous fluid often have this blue color when often have this blue color when viewed from the outside.viewed from the outside.

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SIGNS / SYMPTOMSSIGNS / SYMPTOMS Pain, tenderness, palpable masses, usually multiple and bilateral, Pain, tenderness, palpable masses, usually multiple and bilateral,

worse or sometimes only present during the luteal phase.worse or sometimes only present during the luteal phase. Fluctuation in size of the cysts.Fluctuation in size of the cysts. ““Suspicious” masses should be biopsied.Suspicious” masses should be biopsied. Aspiration of a dominant cyst and / or Bx and /or MMG should be Aspiration of a dominant cyst and / or Bx and /or MMG should be

considered to assist in the Dx, although a MMG negative for considered to assist in the Dx, although a MMG negative for malignancy does not R/O malignancyonly Bx rules out malignancy.malignancy does not R/O malignancyonly Bx rules out malignancy.

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TREATMENTTREATMENT Hormonal therapy theoretically the ticket, but not Hormonal therapy theoretically the ticket, but not

practical long term due to side-effects, risks, etc, practical long term due to side-effects, risks, etc, although these rules can be bent for patients at the although these rules can be bent for patients at the extreme end of the symptomatic spectrum.extreme end of the symptomatic spectrum.

Avoidance of caffeine, Vitamin E 440 IU/d.Avoidance of caffeine, Vitamin E 440 IU/d.

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NIPPLE DISCHARGE

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

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

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NIPPLE DISCHARGE

““A 40 year old female comes in with a 2 month history of a spontaneous 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 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 blood with pressure in the upper outer quadrant of the breast. There is no palpable mass. Your DDx would include…….”palpable mass. Your DDx would include…….”

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NIPPLE DISCHARGE

GALACTORRHEAGALACTORRHEA The discharge of milk from the non-lactating breast.The discharge of milk from the non-lactating breast. Caused by hyperprolactinemia- can be due to: prolactin-Caused by hyperprolactinemia- can be due to: prolactin-

producing adenoma of the pituitary, hypothyroidism, anti-producing adenoma of the pituitary, hypothyroidism, anti-psychotic medication, and other screwy things- see pg 1113.psychotic medication, and other screwy things- see pg 1113.

A serum prolactin should be done. If elevated, a cause should A serum prolactin should be done. If elevated, a cause should be sought.be sought.

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NIPPLE DISCHARGE

EVALUATIONEVALUATION All patients should have a history and PE looking for the 9 All patients should have a history and PE looking for the 9

things listed.things listed. When localization is not possible, there is no palpable mass, When localization is not possible, there is no palpable mass,

the discharge is not bloody, and the MMG is normal, the the discharge is not bloody, and the MMG is normal, the patient should be followed every 3 months for a year, w/ a patient should be followed every 3 months for a year, w/ a repeat MMG in 6-12 months if the discharge persists.repeat MMG in 6-12 months if the discharge persists.

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NIPPLE DISCHARGE

EVALUATIONEVALUATION ALL PATIENTS W/ A UNILATERAL, BLOODY DISCHARGE ALL PATIENTS W/ A UNILATERAL, BLOODY DISCHARGE

SHOULD HAVE AT LEAST AN EXAM AND A MAMMOGRAM. SHOULD HAVE AT LEAST AN EXAM AND A MAMMOGRAM. CONSIDER REFERRAL FOR EXCISION OF THE INVOLVED DUCT.CONSIDER REFERRAL FOR EXCISION OF THE INVOLVED DUCT.

ALL PATIENTS WITH A NEW MASS SHOULD HAVE A BIOPSY OF ALL PATIENTS WITH A NEW MASS SHOULD HAVE A BIOPSY OF SOME SORT. NOT A MAMMOGRAM. A BIOPSY. REGARDLESS SOME SORT. NOT A MAMMOGRAM. A BIOPSY. REGARDLESS OF AGE.OF AGE.

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BREAST CANCER

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

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BREAST CANCER

““Most women w/ breast cancer have no identifiable risk Most women w/ breast cancer have no identifiable risk factor.”factor.”

““There is no history of breast cancer among female relatives There is no history of breast cancer among female relatives in over 75% of patients.”in over 75% of patients.”

1-2% of patients w/ a prior Dx of breast cancer will develop a 1-2% of patients w/ a prior Dx of breast cancer will develop a second primary in the other breast.second primary in the other breast.

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BREAST CANCER

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

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BREAST CANCER

RANDOM CLINICAL PEARLSRANDOM CLINICAL PEARLS 60% of breast cancers develop in the upper-outer quadrant.60% of breast cancers develop in the upper-outer quadrant. SYMPTOMS- SYMPTOMS- 1) A painless lump is the presenting symptom in 70% of 1) A painless lump is the presenting symptom in 70% of

patients w/ breast cancer. patients w/ breast cancer. 2) Less often: discharge, pain, skin retraction, itching of the 2) Less often: discharge, pain, skin retraction, itching of the

nipple, redness, generalized hardnessnipple, redness, generalized hardness..

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BREAST CANCER

RANDOM CLINICAL PEARLSRANDOM CLINICAL PEARLSPHYSICAL FINDINGS- PHYSICAL FINDINGS- hard, non-tender mass, fixed, poorly hard, non-tender mass, fixed, poorly

delineated margins. Skin or nipple retraction.delineated margins. Skin or nipple retraction.

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BREAST CANCER

SCREENINGSCREENING1)Self-breast exams for those interested in it at any age, those 1)Self-breast exams for those interested in it at any age, those

after age 50, and those at increased risk of breast cancer.after age 50, and those at increased risk of breast cancer.2)ALSO: yearly exams by a clinician and annual mammograms 2)ALSO: yearly exams by a clinician and annual mammograms

every 1-2 years after age 40, and yearly after age 50.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 3)A breast cancer can be detected on MMG 2 years before they

can be palpated.can be palpated.

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WHEN TO ORDER A MAMMOGRAM

1) FOR SCREENING.1) FOR SCREENING.2) TO EVALUATE EACH BREAST AFTER THE Dx OF BREAST 2) TO EVALUATE EACH BREAST AFTER THE Dx OF BREAST

CANCER.CANCER.3) TO EVALUATE A BREAST MASS OR OTHER 3) TO EVALUATE A BREAST MASS OR OTHER

ABNORMALITY.ABNORMALITY.4) TO LOOK FOR A PRIMARY WHEN A METASTASIS OF 4) TO LOOK FOR A PRIMARY WHEN A METASTASIS OF

ADENOCARCINOMA IS FOUND.ADENOCARCINOMA IS FOUND.5) TO SCREEN PRIOR TO BIOPSY OR COSMETIC 5) TO SCREEN PRIOR TO BIOPSY OR COSMETIC

PROCEDURES.PROCEDURES.6) FOLLOW-UP AFTER BREAST-CONSERVING SURGERY 6) FOLLOW-UP AFTER BREAST-CONSERVING SURGERY

AND RADIATION.AND RADIATION.

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DISORDERS DUE TO PHYSICAL DISORDERS DUE TO PHYSICAL AGENTSAGENTS

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

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Hypothermia: Cold exposure

Skin temp <25°CSkin temp <25°C At 15°C skin looks pink –leads to tissue ischemiaAt 15°C skin looks pink –leads to tissue ischemia At -4°C to -10° C frostbite (ice crystals inside tissues) occurs-At -4°C to -10° C frostbite (ice crystals inside tissues) occurs-

neuropathic damage occursneuropathic damage occurs Keep warm/ keep dry/ keep movingKeep warm/ keep dry/ keep moving Avoid tobacco and alcoholAvoid tobacco and alcohol

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Hypothermia: Cold exposure

Superficial frostbit (frostnip) steady pressure with warm hand / Do not Superficial frostbit (frostnip) steady pressure with warm hand / Do not rub!rub!

Deep frostbite – rapid warming immediately if safeDeep frostbite – rapid warming immediately if safe If danger refreeze exists do not thawIf danger refreeze exists do not thaw Immerse the part in moving water bath at 40-42°C (Dry heat not Immerse the part in moving water bath at 40-42°C (Dry heat not

recommended)recommended)

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Heat Disorders

Heat syncope-Heat syncope- a hypovolemia syndrome. BP <100. a hypovolemia syndrome. BP <100. Usually vigorous exercise in the preceding 2 hrs Usually vigorous exercise in the preceding 2 hrs precipitates the event. Cool moist skin and weak precipitates the event. Cool moist skin and weak pulse.pulse.

Heat cramps-Heat cramps- lasts 1-3 minutes. Due to sodium loss by lasts 1-3 minutes. Due to sodium loss by sweat. Cool oist skin/ tender muscle. BP OK. Serum sweat. Cool oist skin/ tender muscle. BP OK. Serum sodium low.sodium low.

Keep him cool. Give saline solutionKeep him cool. Give saline solution

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Heat Disorders

Heat Exhaustion-Heat Exhaustion- prolonged vigorous exercise with inadequate salt and prolonged vigorous exercise with inadequate salt and fluid intake. High rectal temperature (>37.8°C) rapid pulse (>120-140)fluid intake. High rectal temperature (>37.8°C) rapid pulse (>120-140)

Exhibit nausea/ vomiting/ myalgia/ thirst/headache/ fatigue/ hysteria/ Exhibit nausea/ vomiting/ myalgia/ thirst/headache/ fatigue/ hysteria/ psychosis. Can progress to heat stroke.psychosis. Can progress to heat stroke.

Keep cool. Hydrate 1-2L in 2 hrs/salt/ fans/ice packKeep cool. Hydrate 1-2L in 2 hrs/salt/ fans/ice pack

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Heat Disorders

Heat StrokeHeat Stroke: Life threatening. Rectal temperature >41°C. Cerebral : Life threatening. Rectal temperature >41°C. Cerebral dysfunction/ impaired consciousness/ high fever/ dysfunction/ impaired consciousness/ high fever/ Absence of sweatingAbsence of sweatingAt risk- very young and very oldAt risk- very young and very oldPatients on medications- anticholinergis/antihistaminesPatients on medications- anticholinergis/antihistaminesCan be seen in marathon runnersCan be seen in marathon runnersHigh mortality-collapse/convulsions/comaHigh mortality-collapse/convulsions/comaReduce core temperature rapidly- ice water immersion/ evaporative Reduce core temperature rapidly- ice water immersion/ evaporative coolingcooling

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Alpha Alpha radiation consists of radiation consists of helium-4 nucleus and is readily helium-4 nucleus and is readily stopped by a sheet of paper. stopped by a sheet of paper.

BetaBeta radiation, consisting of radiation, consisting of electrons, is halted by an electrons, is halted by an aluminium plate. aluminium plate.

GammaGamma radiation is eventually radiation is eventually absorbed as it penetrates a absorbed as it penetrates a dense material. Lead is good at dense material. Lead is good at absorbing gamma radiation, absorbing gamma radiation, due to its densitydue to its density

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Radiation Effects

SkinSkin--MucusMucus membrane- redness/ loss of hair/ exfoliation/ membrane- redness/ loss of hair/ exfoliation/ thermal burnsthermal burns

BMD/ PericarditisBMD/ Pericarditis PneumonitisPneumonitis Oropharyngeal ulcersOropharyngeal ulcers Hepatitis/ nephritisHepatitis/ nephritis GonadsGonads Radiation sickness:Radiation sickness: nausea/ anorexia/ exhaustion nausea/ anorexia/ exhaustion Therapy- Serial lymphocyte counts/ chelation for Therapy- Serial lymphocyte counts/ chelation for

radioisotopesradioisotopes

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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

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First-degree burns affect only the First-degree burns affect only the outer layer of the skin. They cause outer layer of the skin. They cause pain, redness, and swelling.pain, redness, and swelling.

Second-degree (partial thickness) Second-degree (partial thickness) burns affect both the outer and burns affect both the outer and underlying layer of skin. They underlying layer of skin. They cause pain, redness, swelling, and cause pain, redness, swelling, and blistering.blistering.

Third-degree (full thickness) burns Third-degree (full thickness) burns extend into deeper tissues. They extend into deeper tissues. They cause cause white or blackened, charred white or blackened, charred skin that may be numb. skin that may be numb.

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Electrical injuries - uncommon occurrence

500-1000 resultant deaths occur per 500-1000 resultant deaths occur per year year

Factors- the voltage, current Factors- the voltage, current strength, resistance to flow, strength, resistance to flow, duration of contact, pathway of duration of contact, pathway of flow, and type of current. flow, and type of current.

Ohm's law: ‘voltage is equal to Ohm's law: ‘voltage is equal to current times resistance’ current times resistance’

high voltage above 500-1000 Vhigh voltage above 500-1000 V household appliances work at 110 V household appliances work at 110 V Current is the volume of electron Current is the volume of electron

flow –DC or AC flow –DC or AC Frequency 60 Hz Frequency 60 Hz Resistance-impedance to electron Resistance-impedance to electron

flow and usually depends on the flow and usually depends on the water content of a conducting water content of a conducting material material low-voltage electrical injury

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Respiratory muscle paralysis Respiratory muscle paralysis occurs at 20-50 mA. occurs at 20-50 mA.

Ventricular fibrillation may Ventricular fibrillation may develop at 50-120 mA and develop at 50-120 mA and

Asystole, at currents greater than Asystole, at currents greater than 2 A.2 A.

Flash burns- an electrical arc does Flash burns- an electrical arc does not enter the body but just not enter the body but just causes a severe thermal injury causes a severe thermal injury and singe nearby hairs and singe nearby hairs

Ventricular fibrillation is more Ventricular fibrillation is more common with low-voltage AC; common with low-voltage AC; Delayed arrhythmias can occur Delayed arrhythmias can occur up to 12 hours up to 12 hours

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Low-voltage burns

Thermal burns caused by Thermal burns caused by prolonged contact; usually prolonged contact; usually at least several seconds of at least several seconds of contact are required. contact are required.

They almost exclusively They almost exclusively occur in the hands of adults occur in the hands of adults and in the mouths of and in the mouths of children. Children may children. Children may chew on extension cords chew on extension cords and receive an oral burnand receive an oral burn

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About TASER!

Deliver sequential DC pulses, up to 50,000 VDeliver sequential DC pulses, up to 50,000 V Deaths from TASER use have been reportedDeaths from TASER use have been reported A superficial puncture woundA superficial puncture wound The most serious complications are from trauma subsequent The most serious complications are from trauma subsequent

to the shock. to the shock.

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Lightning

A type of high-voltage DC electrical A type of high-voltage DC electrical injury injury

Mild-superficial burns with associated Mild-superficial burns with associated loss of consciousness, amnesia, loss of consciousness, amnesia, confusion, and tingling confusion, and tingling

Moderate injuries-may include seizures, Moderate injuries-may include seizures, respiratory arrest, and cardiac stunning respiratory arrest, and cardiac stunning

Severe lightning injuries-cause Severe lightning injuries-cause cardiopulmonary arrest, with a very low cardiopulmonary arrest, with a very low survival rate. survival rate.

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INFECTIOUS DISEASESINFECTIOUS DISEASES

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NOSOCOMIAL INFECTION

““Those not present or incubating at the time of hospital admission and Those not present or incubating at the time of hospital admission and developing 48-72 hours after admission.”developing 48-72 hours after admission.”

5% of hospitalized patients develop one.5% of hospitalized patients develop one. Carry a 5% mortality rate.Carry a 5% mortality rate. Most common are urinary tract infections.Most common are urinary tract infections. Catheters of all types are associated w/ increased risk of an infection.Catheters of all types are associated w/ increased risk of an infection. Are more often multiple drug resistant.Are more often multiple drug resistant.

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NOSOCOMIAL INFECTION

When looking at cultures, distinguish between colonization and infection.When looking at cultures, distinguish between colonization and infection. PREVENTION- the most effective method of preventing nosocomial PREVENTION- the most effective method of preventing nosocomial

infections is handwashing.infections is handwashing. Hand disinfectants.Hand disinfectants. Change central catheters every 3-4 days.Change central catheters every 3-4 days. Attention to all catheters as a possible source of fever / infection.Attention to all catheters as a possible source of fever / infection.

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INFECTIONS IN DRUG USERS

1) 1) SKIN INFECTIONS-SKIN INFECTIONS- Staph aureus, oral flora (Strep, Pepto-sctreptococci), Staph aureus, oral flora (Strep, Pepto-sctreptococci), gram negatives, depending on injection site, practices etc.gram negatives, depending on injection site, practices etc.

2) 2) HEPATITISHEPATITIS-- B,C, AND D, ALSO A. can have multiple episodes w/ different B,C, AND D, ALSO A. can have multiple episodes w/ different agentsagents

3) 3) ASPIRATION PNEUMONIA-ASPIRATION PNEUMONIA- 4) 4) TB-TB-5) PULMONARY 5) PULMONARY SEPTIC EMBOLI-SEPTIC EMBOLI- from venous thrombi or right-sided from venous thrombi or right-sided

endocarditis.endocarditis.

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6) STDs- 6) STDs- 7) AIDS-HIV7) AIDS-HIV8) INFECTIVE ENDOCARDITIS-8) INFECTIVE ENDOCARDITIS-9) VASCULAR INFECTIONS- 9) VASCULAR INFECTIONS- septic thrombophlebitis, mycotic aneurysms.septic thrombophlebitis, mycotic aneurysms.10) OSTEOMYELITIS AND SEPTIC ARTHRITIS-10) OSTEOMYELITIS AND SEPTIC ARTHRITIS-

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TREATMENT TREATMENT Work-up, cultures etc followed by broad-spectrum antibiotics Work-up, cultures etc followed by broad-spectrum antibiotics

effective against resistant Staph and others, nafcillin or effective against resistant Staph and others, nafcillin or vancomycin combined with gentamicin, depending on CXR, while vancomycin combined with gentamicin, depending on CXR, while awaiting culture results.awaiting culture results.

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ACUTE INFECTIOUS DIARRHEA 11INFLAMMATORYINFLAMMATORY Presence of an invasive pathogen, Presence of an invasive pathogen,

parasite, or a toxin.parasite, or a toxin. Colon commonly affected: Colon commonly affected: frequent, frequent,

bloody, small-volume stools, often bloody, small-volume stools, often fever, cramps, tenesmus, urgency.fever, cramps, tenesmus, urgency.

The Bugs: The Bugs: Shigella, Salmonella, Shigella, Salmonella, Campylobacter, Yersinia, Campylobacter, Yersinia, invasiveinvasive E E coli, Entamoeba histolytica, coli, Entamoeba histolytica, Clostridium dificile (Clostridium dificile (esp in the recently-esp in the recently-hospitalized) hospitalized) ..

Test for fecal leucocytes is positive.Test for fecal leucocytes is positive. Stool culture identifies the bugStool culture identifies the bug..

NON-INFLAMMATORYNON-INFLAMMATORY Milder, small bowel disease. Milder, small bowel disease. Usually viralUsually viral stools are larger volume, stools are larger volume,

non-bloody, watery, w/ non-bloody, watery, w/ nausea, vomiting, cramps, nausea, vomiting, cramps, usually no fever.usually no fever.

The Bugs: Viruses: Norwalk The Bugs: Viruses: Norwalk virus, enteric adenoviruses, virus, enteric adenoviruses, astrovirus, coronavirus; astrovirus, coronavirus; Vibriones: Vibriones: Vibrio choleraVibrio cholera, , Vibrio parahemolyticusVibrio parahemolyticus

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ACUTE INFECTIOUS DIARRHEA

NON-INFLAMMATORYNON-INFLAMMATORY Bugs (cont)- enterotoxin-producing Bugs (cont)- enterotoxin-producing E coliE coli, , Giardia lambliaGiardia lamblia, ,

cryptosporidium, agents causing food-borne gastroenetritis (cryptosporidium, agents causing food-borne gastroenetritis (Staph aureus, Staph aureus, Bacillus cereus, Clostridium perfringensBacillus cereus, Clostridium perfringens).).

TREATMENTTREATMENT Fluid replacement, electrolytes.Fluid replacement, electrolytes. Most acute diarrheas resolve within 3-4 days. Most acute diarrheas resolve within 3-4 days. Those that do not, or those that appear inflammatory, stool cultures Those that do not, or those that appear inflammatory, stool cultures

should be done.should be done.

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TREATMENT TREATMENT Therapy if cultures are positive for: Therapy if cultures are positive for: Shigella, E coliShigella, E coli 0157:H7, 0157:H7,

and and Campylobacter.Campylobacter. For the rest, antibiotic treatment has not been shown to alter For the rest, antibiotic treatment has not been shown to alter

the natural history of the disease, and in fact may prolong the the natural history of the disease, and in fact may prolong the carriage of the bug and lead to relapse/recurrence.carriage of the bug and lead to relapse/recurrence.

Giardiasis treated with metronidazole (Flagyl)Giardiasis treated with metronidazole (Flagyl) Routine use of antibiotics is discouraged due to the Routine use of antibiotics is discouraged due to the

emergence of resistant organisms.emergence of resistant organisms.

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TREATMENT TREATMENT TREAT THOSE:TREAT THOSE: 1) WITH INVASIVE DISEASE.1) WITH INVASIVE DISEASE. 2) WITH SYMPTOMS BEYOND 4 DAYS.2) WITH SYMPTOMS BEYOND 4 DAYS. 3) WITH > 8-10 STOOLS PER DAY.3) WITH > 8-10 STOOLS PER DAY. 4) WHO ARE IMMUNOCOMPROMISED.4) WHO ARE IMMUNOCOMPROMISED. Use anti-spasmodics (Immodium etc) only in those without Use anti-spasmodics (Immodium etc) only in those without

invasive/inflammatory disease (fever, bloody stools).invasive/inflammatory disease (fever, bloody stools).

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TRAVELER’S DIARRHEA

80% are bacterial.80% are bacterial. The Bugs: enterotoxigenic The Bugs: enterotoxigenic E coliE coli, , Campylobacter, ShigellaCampylobacter, Shigella, less frequently , less frequently

Aeromonas, Salmonella, Entamoeba histolyticaAeromonas, Salmonella, Entamoeba histolytica, , Giardia lambliaGiardia lamblia. Viruses: . Viruses: adenoviruses, rotaviruses.adenoviruses, rotaviruses.

Occurring within 1 week of travel, usually benign and self-limiting, Occurring within 1 week of travel, usually benign and self-limiting, resolves within 1-5 days.resolves within 1-5 days.

Frequent, loose BM’s, watery, non-bloody, cramps, N/V, no feverFrequent, loose BM’s, watery, non-bloody, cramps, N/V, no fever

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TRAVELER’S DIARRHEA

If stools are bloody, or fever is present → stool cultures and treatment.If stools are bloody, or fever is present → stool cultures and treatment. Empiric treatment w/ Cipro 500 mg bid for 3-5 days, other Empiric treatment w/ Cipro 500 mg bid for 3-5 days, other

fluoroquinolones, trim-sulfa.fluoroquinolones, trim-sulfa. Specific treatment may change w/ culture results, but often not.Specific treatment may change w/ culture results, but often not. See text re prophylaxis.See text re prophylaxis.

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HIV INFECTIONHIV INFECTION

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Post Exposure: Early Symptoms

Flu-like illness within a month or two after exposure to the Flu-like illness within a month or two after exposure to the virus. This illness may includevirus. This illness may include

Fever Fever Headache Headache Tiredness Tiredness Enlarged lymph nodes Enlarged lymph nodes

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Later Symptoms

Asymptomatic 10-15 yearsAsymptomatic 10-15 years During the asymptomatic period, the virus is actively During the asymptomatic period, the virus is actively

multiplying multiplying Results in a decline in the number of CD4 positive T (CD4+) Results in a decline in the number of CD4 positive T (CD4+)

cells cells

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Late Symptoms (?AIDS) The first signs of infection are large lymph nodes, or swollen glands that may be The first signs of infection are large lymph nodes, or swollen glands that may be

enlarged for more than 3 months. enlarged for more than 3 months. Other symptoms often experienced months to years before the onset of AIDS Other symptoms often experienced months to years before the onset of AIDS

include:include: Lack of energy Lack of energy Weight loss Weight loss Frequent fevers and sweats Frequent fevers and sweats Persistent or frequent yeast infections (oral or vaginal) Persistent or frequent yeast infections (oral or vaginal) Persistent skin rashes or flaky skin Persistent skin rashes or flaky skin Pelvic inflammatory disease in women that does not respond to treatment Pelvic inflammatory disease in women that does not respond to treatment Short-term memory loss Short-term memory loss Frequent and severe herpes infections that cause mouth, genital, or anal sores, or Frequent and severe herpes infections that cause mouth, genital, or anal sores, or

shinglesshingles

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“Opportunistic infections” = AIDS

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

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CD4+ (Helper) T cell Counts

Normal >800-1600Normal >800-1600 Risk increases for counts <400Risk increases for counts <400 AIDS if <200AIDS if <200 Diagnosis – ‘HIV positive’- carrier of the diseaseDiagnosis – ‘HIV positive’- carrier of the disease ELISA screen usually positive 1-3 months after exposure (up to 6 months)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 Likely to develop antibodies to the virus-within 6 weeks to 12 months Western blot technique required to confirm ELISA testWestern blot technique required to confirm ELISA test

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?THERAPY

No Cure!No Cure! reverse transcriptase (RT) inhibitors reverse transcriptase (RT) inhibitors (Nucleoside/nucleotide inhibitors)(Nucleoside/nucleotide inhibitors) protease inhibitors, interrupt the virus from making copies protease inhibitors, interrupt the virus from making copies

of itself at a later step in its life cycle of itself at a later step in its life cycle fusion inhibitors - Fuzeon (enfuvirtide or T-20)fusion inhibitors - Fuzeon (enfuvirtide or T-20) highly active antiretroviral therapy, or HAART highly active antiretroviral therapy, or HAART

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?Side Effects

Bone marrow depressionBone marrow depression Pancreatitis/ PolyneuritisPancreatitis/ Polyneuritis GI and Respiratory symptomsGI and Respiratory symptoms Other severe reactions, including death Other severe reactions, including death

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Therapy for opportunistic infections

Foscarnet and ganciclovir to treat CMV (cytomegalovirus) eye infections Foscarnet and ganciclovir to treat CMV (cytomegalovirus) eye infections Fluconazole to treat yeast and other fungal infections Fluconazole to treat yeast and other fungal infections TMP/SMX (Bactrim® or Septra®) (trimethoprim/sulfamethoxazole) or TMP/SMX (Bactrim® or Septra®) (trimethoprim/sulfamethoxazole) or

pentamidine to treat PCP (Pneumocystis carinii pneumonia) pentamidine to treat PCP (Pneumocystis carinii pneumonia) Cancer therapy for NHL/ Kaposi’s SarcomaCancer therapy for NHL/ Kaposi’s Sarcoma

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LYME DISEASE

Lyme borreliosis, caused by Lyme borreliosis, caused by Borrelia burgdorferiBorrelia burgdorferi, a spirochete., a spirochete. The vector is the ixodid tick, of which there are 4 genomic The vector is the ixodid tick, of which there are 4 genomic

groups.groups. Mostly seen in the northeast, north central, and mid-Atlantic Mostly seen in the northeast, north central, and mid-Atlantic

states.states. Accuracy of diagnosis is suspect, as patients are diagnosed Accuracy of diagnosis is suspect, as patients are diagnosed

with Lyme disease in areas where there is no known with Lyme disease in areas where there is no known host/cycle for host/cycle for B burgdorferi.B burgdorferi.

Concerns about over diagnosis. See text.Concerns about over diagnosis. See text.

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LYME DISEASE

CLINICALCLINICAL 3 STAGES3 STAGES

1) STAGE 1- EARLY LOCALIZED INFECTION.1) STAGE 1- EARLY LOCALIZED INFECTION. 2) STAGE 2- EARLY DISSEMINATED INFECTION.2) STAGE 2- EARLY DISSEMINATED INFECTION. 3) STAGE 3- LATE PERSISTENT INFECTION.3) STAGE 3- LATE PERSISTENT INFECTION.

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LYME DISEASE

CLINICALCLINICAL STAGE 1 - EARLY LOCALIZED INFECTIONSTAGE 1 - EARLY LOCALIZED INFECTION ERYTHEMA MIGRANS.ERYTHEMA MIGRANS. 1 week-10 days after the tick bite, at the site of the tick bite1 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.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 Classic description is the “Bull’s Eye” lesion, but a more heterogenous lesion is

common.common. 50% have a flu-like illness.50% have a flu-like illness. Resolves w/ out treatment in 3-4 weeks.Resolves w/ out treatment in 3-4 weeks.

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56,300 people were newly infected with HIV in 2006 (the 56,300 people were newly infected with HIV in 2006 (the most recent year that data are available). most recent year that data are available).

Over half (53%) of these new infections occurred in gay and Over half (53%) of these new infections occurred in gay and bisexual men. bisexual men.

Black/African American men and women were also strongly Black/African American men and women were also strongly affected and were estimated to have an incidence rate than affected and were estimated to have an incidence rate than was 7 times as high as the incidence rate among whites. was 7 times as high as the incidence rate among whites.

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LYME DISEASECLINICALCLINICAL

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

seroconversion.seroconversion.

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LYME DISEASE

CLINICALCLINICAL STAGE 2 - EARLY DISSEMINATED INFECTIONSTAGE 2 - EARLY DISSEMINATED INFECTION Hematogenous or lymphatic spread.Hematogenous or lymphatic spread. Wide variety of symptoms.Wide variety of symptoms. Days to weeks after the tick bite.Days to weeks after the tick bite. SKIN-SKIN- secondary lesions not in the area of the tick bite, similar to the secondary lesions not in the area of the tick bite, similar to the

lesions in stage 1 but smaller.lesions in stage 1 but smaller. CNS-CNS- headache, stiff neck. headache, stiff neck. MUSCULOSKELETALMUSCULOSKELETAL- migratory pains in joints, muscles, tendons.- migratory pains in joints, muscles, tendons. Fatigue and malaise.Fatigue and malaise.

83

LYME DISEASE

CLINICALCLINICAL STAGE 2 - EARLY DISSEMINATED INFECTIONSTAGE 2 - EARLY DISSEMINATED INFECTION Neurologic & musculoskeletal symptoms last hours to weeks, fatigue is Neurologic & musculoskeletal symptoms last hours to weeks, fatigue is

persistent.persistent. See text for what happens next- the organism sequesters itself in certain See text for what happens next- the organism sequesters itself in certain

areas and produces focal symptoms: cardiac, neurologic, encephalitis, etc.areas and produces focal symptoms: cardiac, neurologic, encephalitis, etc.

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LYME DISEASE

CLINICALCLINICAL STAGE 3 – LATE PERSISTENT INFECTIONSTAGE 3 – LATE PERSISTENT INFECTION Months to years after initial infection.Months to years after initial infection. Possibly an immunologic event rather than persistent Possibly an immunologic event rather than persistent

infection – see pg 1490.infection – see pg 1490. Again: Skin, Neurologic, and Musculoskeletal.Again: Skin, Neurologic, and Musculoskeletal. MUSCULOSKELETAL- MUSCULOSKELETAL- Up to 60%. Sxs are highly variable.Up to 60%. Sxs are highly variable. Arthritis, joint pain w/out objective findings, chronic synovitis.Arthritis, joint pain w/out objective findings, chronic synovitis.

85

LYME DISEASE

CLINICALCLINICAL STAGE 3 – LATE PERSISTENT INFECTIONSTAGE 3 – LATE PERSISTENT INFECTION NERVOUS SYSTEMNERVOUS SYSTEM Both peripheral and central.Both peripheral and central. ““Subacute encephalopathy”- memory loss, mood swings, sleep Subacute encephalopathy”- memory loss, mood swings, sleep

disturbance.disturbance. Axonal polyneuropathy.Axonal polyneuropathy.

86

LYME DISEASE

CLINICALCLINICAL STAGE 3 – LATE PERSISTENT INFECTIONSTAGE 3 – LATE PERSISTENT INFECTION SKINSKIN ACRODERMATITIS CHRONICUM ATROPHICANSACRODERMATITIS CHRONICUM ATROPHICANS Can occur up to 10 years later.Can occur up to 10 years later. Not common in the U.S., mostly in Europe due to a different species of Not common in the U.S., mostly in Europe due to a different species of B B

burgdorferi.burgdorferi.

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LYME DISEASE

CLINICALCLINICAL Dx based on both clinical and lab findings.Dx based on both clinical and lab findings. Dx CRITERIA: Exposure to a “potential tick habitat” within 30 days prior to Dx CRITERIA: Exposure to a “potential tick habitat” within 30 days prior to

developing erythema migrans WITH:developing erythema migrans WITH: 1) Erythema migrans Dx’d by a physician, 1) Erythema migrans Dx’d by a physician, OROR 2) One late manifestation, 2) One late manifestation, ANDAND 3) Laboratory confirmation.3) Laboratory confirmation.

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LYME DISEASE

CLINICALCLINICALLABLAB

See text for details of the assay, the ELISA, western blot, etc.See text for details of the assay, the ELISA, western blot, etc. Detect antibodies to Detect antibodies to B. burgdorferiB. burgdorferi.. See text for Dx criteria by the American College of Physicians. True See text for Dx criteria by the American College of Physicians. True

positives vs. false positives. Read this. Really.positives vs. false positives. Read this. Really. ““Patients w/ non-specific symptoms without objective signs of Lyme Patients w/ non-specific symptoms without objective signs of Lyme

disease disease should notshould not have serologic testing done.” In this setting, false have serologic testing done.” In this setting, false positives occur more commonly than true positives.positives occur more commonly than true positives.

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LYME DISEASE

TREATMENTTREATMENT Tetracycline, ampicillin, ceftriaxone, azithromycin, cefuroxime, imipenem.Tetracycline, ampicillin, ceftriaxone, azithromycin, cefuroxime, imipenem. A Dx of Erythema migrans by a physician warrants immediate treatment w/ no A Dx of Erythema migrans by a physician warrants immediate treatment w/ no

other diagnostic tests.other diagnostic tests. Treatment dependent on clinical manifestations, see table 34-4 pg 1492.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 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 one w/ CONFIRMATION by serologic tests, and that the serologic tests are fraught w/ difficulty.w/ difficulty.

Beware of the patient presenting demanding treatment for his/her Lyme disease.Beware of the patient presenting demanding treatment for his/her Lyme disease.

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LYME DISEASE

TREATMENTTREATMENT Oral therapy for most cases, weeks usually.Oral therapy for most cases, weeks usually. IV therapy for patients with neurologic / CNS manifestations.IV therapy for patients with neurologic / CNS manifestations. Most patients will have prompt resolution of symptoms within 4 weeks of Most patients will have prompt resolution of symptoms within 4 weeks of

completing therapy.completing therapy. ““True treatment failures are uncommon.”True treatment failures are uncommon.” See pg 1493 re patients treated for Lyme Disease who have persistent symptoms, 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 productiveand 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.Life long immunity is not complete, pts are subject to re-infection.

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CLINICAL FINDINGS

1) 1) SYSTEMIC COMPLAINTS- SYSTEMIC COMPLAINTS- Fever, night sweats, weight loss, even in the absence of an infection, but a Fever, night sweats, weight loss, even in the absence of an infection, but a

work-up is in order for the patient w/ fever.work-up is in order for the patient w/ fever.2) 2) SINOPULMONARY DISEASE-SINOPULMONARY DISEASE-

PNEUMOCYSTIS JIROVECIPNEUMOCYSTIS JIROVECI (yee row vet zee)- the “new”, though not yet (yee row vet zee)- the “new”, though not yet universally accepted, name of universally accepted, name of Pneumocystis cariniiPneumocystis carinii, and its pneumonia is , and its pneumonia is the most common opportunistic infection associated w/ AIDS. Formerly the most common opportunistic infection associated w/ AIDS. Formerly called PCP pneumonia.called PCP pneumonia.

92

CLINICAL FINDINGS

2) 2) SINOPULMONARY DISEASE-SINOPULMONARY DISEASE- Sxs of PCP can be vague, findings non-specific.Sxs of PCP can be vague, findings non-specific. Dx is made based on CXR sputum cultures.Dx is made based on CXR sputum cultures. Most cases of PCP occur at CD4 counts below 200, at which point Most cases of PCP occur at CD4 counts below 200, at which point

prophylaxis is given the uninfected patient.prophylaxis is given the uninfected patient. TBTB- as well as atypical Mycobacteria such as Mycobacterium avium.- as well as atypical Mycobacteria such as Mycobacterium avium. COMMUNITY-ACQUIRED PNEUMONIA-COMMUNITY-ACQUIRED PNEUMONIA- the most common cause of the most common cause of

pulmonary disease in HIV.pulmonary disease in HIV.

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CLINICAL FINDINGS

2) 2) SINOPULMONARY DISEASE-SINOPULMONARY DISEASE- SINUSITISSINUSITIS- tends to be chronic.- tends to be chronic. NONINFECTIOUS PULMONARY DISEASE-NONINFECTIOUS PULMONARY DISEASE- Kaposi’s sarcoma, non-Hodgkin’s Kaposi’s sarcoma, non-Hodgkin’s

lymphoma.lymphoma.3) 3) CNS DISEASECNS DISEASE

TOXOPLASMOSIS.TOXOPLASMOSIS. LYMPHOMA.LYMPHOMA. AIDS DEMENTIA.AIDS DEMENTIA. CRYPTOCOCCAL MENINGITIS- w/ CRYPTOCOCCAL MENINGITIS- w/ Cryptococcus neoformans.Cryptococcus neoformans.

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CLINICAL FINDINGS

3) 3) CNS DISEASECNS DISEASE HIV MYELOPATHY.HIV MYELOPATHY. PROGRESSIVE MULTIFOCAL LEOKOENCEPHALOPATHY (PML).PROGRESSIVE MULTIFOCAL LEOKOENCEPHALOPATHY (PML).

4) 4) PERIPHERAL NERVOUS SYSTEMPERIPHERAL NERVOUS SYSTEM INFLAMMATORY POLYNEUROPATHIES.INFLAMMATORY POLYNEUROPATHIES. SENSORY NEUROPATHY.SENSORY NEUROPATHY. MONONEUROPATHIES.MONONEUROPATHIES. Treatment aimed at symptomatic relief- Neurontin (gabapentin).Treatment aimed at symptomatic relief- Neurontin (gabapentin).

95

CLINICAL FINDINGS

5) 5) RHEUMATOLOGICRHEUMATOLOGIC ARTHRITIS.ARTHRITIS. OTHER RHEUMATOLOGIC SYNDROMES- lupus, Reiter’s OTHER RHEUMATOLOGIC SYNDROMES- lupus, Reiter’s

syndrome, psoriatic arthritis.syndrome, psoriatic arthritis.6) 6) MYOPATHYMYOPATHY

Proximal muscle weakness.Proximal muscle weakness. Need to distinguish it from the myopathy as a side effect of Need to distinguish it from the myopathy as a side effect of

zidovudine therapy.zidovudine therapy.

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CLINICAL FINDINGS

7) 7) RETINITISRETINITIS CMV- most common retinal infection in HIV.CMV- most common retinal infection in HIV.

8) 8) ORAL LESIONSORAL LESIONS ORAL CANDIDIASIS.ORAL CANDIDIASIS. HAIRY LEUKOPLAKIA- caused by EBV.HAIRY LEUKOPLAKIA- caused by EBV. ANGULAR CHELITIS.ANGULAR CHELITIS. APHTHOUS ULCERS.APHTHOUS ULCERS.

9) 9) GASTROINTESTINALGASTROINTESTINAL ESOPHAGEAL CANDIDIASIS-ESOPHAGEAL CANDIDIASIS-

97

CLINICAL FINDINGS

9) 9) GASTROINTESTINALGASTROINTESTINAL HEPATIC DISEASE- various infections, and progression from the chronic HEPATIC DISEASE- various infections, and progression from the chronic

carrier state of hepatitis B and C to cirrhosis, liver failure, and carcinoma.carrier state of hepatitis B and C to cirrhosis, liver failure, and carcinoma. BILIARY DISEASE- cholecystitis, sclerosing cholangitis.BILIARY DISEASE- cholecystitis, sclerosing cholangitis. ENTEROCOLITIS- COMMON. Bacteria: ENTEROCOLITIS- COMMON. Bacteria: Campylobacter, Salmonella, Campylobacter, Salmonella,

ShigellaShigella. Viruses: CMV, adenoviruses. Protozoans: . Viruses: CMV, adenoviruses. Protozoans: Cryptosporidium,Giardia, Entamoeba histolytica, Isospora.Cryptosporidium,Giardia, Entamoeba histolytica, Isospora.

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CLINICAL FINDINGS

9) 9) GASTROINTESTINALGASTROINTESTINAL ENTEROCOLITIS- symptomati patients should have stool ENTEROCOLITIS- symptomati patients should have stool

culture, O&P. If negative, colonoscopy, Bx. If all negative culture, O&P. If negative, colonoscopy, Bx. If all negative presumptive Dx of AIDS Enteropathy.presumptive Dx of AIDS Enteropathy.

GASTROPATHY- inadequate acid production → increased GASTROPATHY- inadequate acid production → increased susceptibility to susceptibility to Campylobacter, Salmonella, ShigellaCampylobacter, Salmonella, Shigella, poor , poor absorption of drugs.absorption of drugs.

MALABSORPTION- idiopathic vs infection with MALABSORPTION- idiopathic vs infection with Cryptosporidium, Mycobacterium avium.Cryptosporidium, Mycobacterium avium.

99

CLINICAL FINDINGS

10) 10) ENDOCRINEENDOCRINE HYPOGONADISM.HYPOGONADISM. ADRENAL INVOLVEMENT AND HYPOFUNCTION.ADRENAL INVOLVEMENT AND HYPOFUNCTION. THYROID DYSFUNCTION.THYROID DYSFUNCTION.

11) 11) SKIN MANIFESTATIONSSKIN MANIFESTATIONS HERPES SIMPLEX.HERPES SIMPLEX. HERPES ZOSTER.HERPES ZOSTER. MOLLUSCUM CONTAGIOSUM.MOLLUSCUM CONTAGIOSUM. FOLLICULITIS, FURUNCULOSIS, IMPETIGOFOLLICULITIS, FURUNCULOSIS, IMPETIGO

100

CLINICAL FINDINGS

12)12) HIV-RELATED MALIGNANCIESHIV-RELATED MALIGNANCIES ANAL DYSPLASIA AND SQUAMOUS CELL CARCINOMA- from HPV.ANAL DYSPLASIA AND SQUAMOUS CELL CARCINOMA- from HPV. CERVICAL DYSPLASIA AND CARCINOMA- from HPV.CERVICAL DYSPLASIA AND CARCINOMA- from HPV.

13)13) GYNECOLOGIC MANIFESTATIONSGYNECOLOGIC MANIFESTATIONS VAGINAL CANDIDIASIS.VAGINAL CANDIDIASIS. CERVICAL DYSPLASIA AND NEOPLASIA.CERVICAL DYSPLASIA AND NEOPLASIA. PID.PID.

101

CLINICAL FINDINGS

14) 14) INFLAMMATORY REACTIONSINFLAMMATORY REACTIONS IMMUNE RECONSTITUTION SYNDROMES OR “IRIS.”- as the immune IMMUNE RECONSTITUTION SYNDROMES OR “IRIS.”- as the immune

system improves and CD4 count rises with initiation of antiretroviral system improves and CD4 count rises with initiation of antiretroviral therapy.therapy.

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RISK TO HEALTHCARE PROFESSIONALS

RISKRISK Risk of HIV transmission from a single needle stick from an Risk of HIV transmission from a single needle stick from an

HIV-infected patient is about 1:300.HIV-infected patient is about 1:300. Risk is higher w/: deep puncture, large inoculum, high viral Risk is higher w/: deep puncture, large inoculum, high viral

load.load. Risk from mucous membrane exposure is too low to Risk from mucous membrane exposure is too low to

quantitate.quantitate. Follow universal precautions, no recapping, etc.Follow universal precautions, no recapping, etc.

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NEEDLE STICK CONSELING, PROPHYLAXIS NEEDLE STICK CONSELING, PROPHYLAXIS After a needle-stick, counseling, HIV testing, baseline, retested at 6 After a needle-stick, counseling, HIV testing, baseline, retested at 6

weeks, 3 months, 6 months.weeks, 3 months, 6 months.POST-EXPOSURE PROPHYLAXISPOST-EXPOSURE PROPHYLAXIS

Treatment w/ zidovudine reduces seroconversion by 79%.Treatment w/ zidovudine reduces seroconversion by 79%. Providers should be offered some form of post-exposure prophylaxis.Providers should be offered some form of post-exposure prophylaxis.

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POST-EXPOSURE PROPHYLAXISPOST-EXPOSURE PROPHYLAXIS Therapy modified in the face of source-patient who has a high viral load, Therapy modified in the face of source-patient who has a high viral load,

drug resistance.drug resistance. Prophylaxis should begin ASAP, continued for 4 weeks.Prophylaxis should begin ASAP, continued for 4 weeks. Not 100% effective at reducing seroconversion.Not 100% effective at reducing seroconversion. ““Safe sex” talk also needs to happen.Safe sex” talk also needs to happen.

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POST-EXPOSURE PROPHYLAXIS AFTER SEXUAL AND DRUG USE EXPOSUREPOST-EXPOSURE PROPHYLAXIS AFTER SEXUAL AND DRUG USE EXPOSURE Hard data does not exist, but there are similarities between the immune Hard data does not exist, but there are similarities between the immune

response following transcutaneous and mucosal exposure.response following transcutaneous and mucosal exposure. Regimen similar to that for needle sticks in healthcare workers.Regimen similar to that for needle sticks in healthcare workers. Not recommended after 72 hours.Not recommended after 72 hours.

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POST-EXPOSURE PROPHYLAXIS AFTER SEXUAL AND DRUG USE EXPOSUREPOST-EXPOSURE PROPHYLAXIS AFTER SEXUAL AND DRUG USE EXPOSURE

Should occur w/ appropriate counseling re how to prevent further Should occur w/ appropriate counseling re how to prevent further exposure- clean needles, “safe” sex, etc.exposure- clean needles, “safe” sex, etc.

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PROGNOSIS

Improving.Improving. 1995- 50,610 deaths.1995- 50,610 deaths. 1999- 16,273 deaths.1999- 16,273 deaths. The ticket is access to healthcare and appropriate The ticket is access to healthcare and appropriate

antiretroviral therapy w/ ability to monitor CD4 counts, viral antiretroviral therapy w/ ability to monitor CD4 counts, viral loads, to tailor therapy to each patient, including appropriate loads, to tailor therapy to each patient, including appropriate prophylaxis etc.prophylaxis etc.

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PREVENTION OF PERINATAL TRANSMISSION

In the absence of prophylaxis, between 13% and 40% of In the absence of prophylaxis, between 13% and 40% of infants born to HIV+ women become infected.infants born to HIV+ women become infected.

Risk is higher w/ vaginal birth, high viral loads.Risk is higher w/ vaginal birth, high viral loads. Also transmitted via breast milk- HIV+ women should NOT Also transmitted via breast milk- HIV+ women should NOT

breast feed.breast feed.PREVENTIONPREVENTION

Treatment antepartum, intrapartum, and postpartum reduces Treatment antepartum, intrapartum, and postpartum reduces transmission by as much as 2/3.transmission by as much as 2/3.

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Antimycotics Affecting Membrane Structure/Function

Ketoconazole (nizoral®)/ Itraconazole (sporanox®) / Fluconazole (diflucan®)Ketoconazole (nizoral®)/ Itraconazole (sporanox®) / Fluconazole (diflucan®)(safest) (imidazoles):(safest) (imidazoles): cryptococcus, blastomycosis, candida species, dermatophytescryptococcus, blastomycosis, candida species, dermatophytes

Amphotericin-B: toxic but useful for systemic fungal infectionsAmphotericin-B: toxic but useful for systemic fungal infections

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•Terbinafine:•( lamisil®)•Dermatophytes, nail Dermatophytes, nail infections (onychomycosis)infections (onychomycosis)•Blocks ergosterol synthesis•GI upset/Headaches

•Nystatin: (mycostatin®)•Local application to skin, mucus membranes•Candida species,- oral Candida species,- oral and vaginal thrush, and vaginal thrush, intertrigointertrigo

•AZOLES- clotrimazole, (lotrimin®), miconazole, (micatin®)•Vulvovaginal candidiasisVulvovaginal candidiasis•Dermatophytes, Dermatophytes, •Tinea: corporis/ pedis/ crurisTinea: corporis/ pedis/ cruris•Seborrheic dermatitisSeborrheic dermatitis•Pityriasis versicolorPityriasis versicolor

Other Antifungal Agents

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5-Flucytosine (ancobon®)

• • analog of endogenous nucleotideanalog of endogenous nucleotide• • competitively inhibits RNA synthesiscompetitively inhibits RNA synthesis• • mammalian cells unable to convert parent drug to metabolitesmammalian cells unable to convert parent drug to metabolites- bone marrow toxicity - anemia, leukopenia- bone marrow toxicity - anemia, leukopenia• • resistance due to altered metabolism of 5-flucytosine can resistance due to altered metabolism of 5-flucytosine can

emerge rapidly; use combination therapyemerge rapidly; use combination therapy- Cryptococcal meningitsCryptococcal meningits

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HAART facts:• • A very effective combination A very effective combination

therapy for HIV consists of-therapy for HIV consists ofzidovudine (AZT), lamivudine zidovudine (AZT), lamivudine (3TC) and protease inhibitor (3TC) and protease inhibitor (Indinavir)(Indinavir)

••A major problem with these A major problem with these complicated drug regimens is complicated drug regimens is compliance!compliance!

Partly related to drug side/toxic Partly related to drug side/toxic effectseffects

• • In patients that fail to take the three In patients that fail to take the three drugs for a week, there is a rise in drugs for a week, there is a rise in viral load.viral load.

• • Non-compliance Non-compliance • • The HAART is very expensive, for The HAART is very expensive, for

example the combination ofexample the combination ofzidovudine/lamivudine/protease zidovudine/lamivudine/protease inhibitor costsinhibitor costs

$20,000 (US) per year$20,000 (US) per year

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Anti-Hepatitis Agents

Hepatitis B-Hepatitis B- Lamivudine- Lamivudine-

cytosine analog (97% suppression cytosine analog (97% suppression in 2 weeks) recurs in 80% after in 2 weeks) recurs in 80% after ceasing therapyceasing therapy

Adefovir-Adefovir-nucleoside analognucleoside analog

Interferon alfa-2b- Interferon alfa-2b- loss of loss of

HBeAg 30% improvementHBeAg 30% improvement

Hepatitis C-genotype 2,3Hepatitis C-genotype 2,3 Interferon alfa-2b- Interferon alfa-2b-

15-30% response (on no therapy) / 15-30% response (on no therapy) / 98% clearance 98% clearance on therapyon therapy

Peg* interferon alfa-2aPeg* interferon alfa-2a Peg interferon alfa-2b- Peg interferon alfa-2b- increased ½ lifeincreased ½ life, ,

less frequent dosing; less frequent dosing; not superior to IF-alfa2bnot superior to IF-alfa2b

*Peg= Poly Ethylene Glycol*Peg= Poly Ethylene Glycol

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Ribavarin (Virazole®)

Guanosine analogGuanosine analog Effective against influenza A, B, resp. syncytial virus, HCV, HIV-1Effective against influenza A, B, resp. syncytial virus, HCV, HIV-1 Avialable anti flu therapy: neuraminidase inhibitorsAvialable anti flu therapy: neuraminidase inhibitors TamifluTamifluⓇⓇ:(Osletamivir):(Osletamivir) RelenzaRelenzaⓇⓇ: (Zanamivir): (Zanamivir) ?Flu vaccines-?Flu vaccines-

Trivalent inactivated vaccine (TIV)Trivalent inactivated vaccine (TIV)Live attenuated influenza virus (LAIV)Live attenuated influenza virus (LAIV)

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Antimycobacterial Drugs

• • tuberculosis (tuberculosis (Mycobacteria)Mycobacteria)OverviewOverview• • among the leading causes of death from infectious disease (primarily among the leading causes of death from infectious disease (primarily

tuberculosis)tuberculosis)• • infections are among the most difficult to cureinfections are among the most difficult to cureSpecial Characteristics of MycobacteriaSpecial Characteristics of Mycobacteria• • slow growth rateslow growth rate- relatively resistant to antibiotics that depend on a rapid rate of division- relatively resistant to antibiotics that depend on a rapid rate of division- dormancy is possible (long-term treatment; months-years)- dormancy is possible (long-term treatment; months-years)

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At risk group for Tb

Older individualsOlder individuals Immune suppressed group- HIV/ Immune suppressed group- HIV/

Steroid & Immunosuprressant Steroid & Immunosuprressant drug usersdrug users

DiabeticsDiabetics AlcoholicsAlcoholics Diagnostic tool: Manotux Diagnostic tool: Manotux

(tuberculin) skin test(tuberculin) skin test

Clinical features-Clinical features- Weight lossWeight loss Night fever and sweatsNight fever and sweats Dry hacking coughDry hacking cough HemoptysisHemoptysis LymphadenopathyLymphadenopathy Tubercular meningitisTubercular meningitis

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Standard therapy:

1.1. IsoniazidIsoniazid2.2. RifampinRifampin3.3. PyrazinamidePyrazinamide4.4. EthambutolEthambutolAll 4 Drugs for first 2 monthsAll 4 Drugs for first 2 monthsDrugs 1&2 only for next 4 monthsDrugs 1&2 only for next 4 months

Drug side effects-Drug side effects- HepatitisHepatitis NeuritisNeuritis Optic neuritis/ color blindnessOptic neuritis/ color blindness

1 Breast Pathology. 2 Lymphatic drainage Anatomy of Breast.

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Transcript of 1 Breast Pathology. 2 Lymphatic drainage Anatomy of Breast.