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Reproductive Pathophysiology Delayed Puberty Secondary sex characteristics have not appeared in girls by age 13 Secondary sex characteristics have not appeared in boys by age 14 95% of cases are simply a physiologic delay – hormonal levels are normal and the HPG axis is intact, maturation is happeni...

Reproductive Pathophysiology Delayed Puberty Secondary sex characteristics have not appeared in girls by age 13 Secondary sex characteristics have not appeared in boys by age 14 95% of cases are simply a physiologic delay – hormonal levels are normal and the HPG axis is intact, maturation is happening slowly; greater in boys and tends to be familial 5% are caused by some type of disruption of the hypothalamic-pituitary-gonadal axis – chronic condition that delays bone aging; celiac disease, anorexia, hypothyroidism Precocious puberty Sexual maturation before age 6 in black girls and age 7 in white girls Sexual maturation before age 9 in boys More common in girls Complete – sex appropriate; onset of all pubertal features Mixed – not sex appropriate; virilization of a girl or feminization of a boy Partial – development of one secondary sex characteristic only; can be in combination Disorders of the Female Reproductive System Primary dysmenorrhea – painful menstruation associated with prostaglandin release in ovulatory cycles but not with pelvic disease; related to the duration and amount of menstrual flow Secondary dysmenorrhea – painful menstruation related to pelvic pathology; can occur any time in the menstrual cycle Amenorrhea is the lack of menstruation – most common cause is pregnancy ○ Primary amenorrhea – absence of menstruation by age 14 without development of secondary sex characteristics and by age 16 regardless of the presence of secondary sex characteristics ○ Secondary amenorrhea – absence of menstruation for a time equivalent to three or more cycles or 6 months in women who have previously menstruated; associated with anovulation Dysfunctional uterine bleeding (DUB) – heavy or irregular bleeding in the absence of organic disease; perimenopausal women are most affected Polycystic ovarian syndrome (PCOS) – oligo-ovulation or anovulation and elevated levels of androgens or clinical signs of hyperandrogenism and polycystic ovaries ○ Leading cause of infertility in the United States; result of prolonged anovulation ○ Hyperandrogenic state is cardinal feature ○ Glucose intolerance/insulin resistance (IR) and hyperinsulinemia are also common, and aggravate the hyperandrogenic state, therefore further contributing to symptoms; individuals are commonly obese which adds to IR ○ Results in infertility, menstrual bleeding disorders, hirsutism, acne, endometrial hyperplasia, CV disease, and DM, obesity common ○ The high levels of insulin stimulates androgen secretion by the ovarian stroma and reduces hormone-binding globulin; net effect is increase in free testosterone levels Premenstrual syndrome (PMS) – cyclic physical, psychological, or behavioral changes that impair interpersonal relationships or interfere with usual activities ○ Occurs in luteal phase of menstrual cycle ○ Emotional symptoms include depression, anger, irritability, and fatigue ○ Physical symptoms less problematic; water retention, bloating, weight gain; result of sex steroid interacting with RAAS ○ Biologic response triggered by fluctuating estrogen and progesterone levels ○ Serotonin, GABA, and noradrenaline may have mediating roles on symptom manifestation Pelvic inflammatory disease (PID) ○ Acute inflammatory disease caused by infection ○ May involve any organ of the reproductive tract Salpingitis – inflammation of the fallopian tubes Oophoritis – inflammation of the ovaries ○ Sexually transmitted diseases migrate from the vagina to the upper genital tract; chlamydia and Gonorrhea most common ○ Patho – failure of numerous defense mechanisms Vaginitis – infection of the vagina ○ Sexually transmitted pathogens, bacterial vaginosis, and Candida albicans ○ Acidic nature of the vagina provides some protection; maintained by cervical secretions, normal flora, and lactobacillus acidophilus ○ Development is related to the overall health of a woman and local defense mechanisms (vaginal pH very important) ○ Antibiotics, douching, soaps, feminine hygiene sprays, and pregnancy alter vaginal pH and predispose women to infection Bartholinitis – also called Bartholin cyst ○ Inflammation of one or both ducts that lead from the vaginal opening to the Bartholin glands ○ Caused by microorganisms that infect the lower female reproductive tract or trauma ○ Inflammation narrows the distal portion of the ducts ○ Leads to obstruction and stasis of glandular secretions Pelvic Relaxation Disorders Cystocele and rectocele – descent of a portion of the posterior bladder wall and trigone into the vaginal canal. ○ Usually a result of trauma of childbirth Urethrocele – sagging of the urethra ○ Commonly associated with cystocele, especially with women with urinary stress incontinence ○ Caused by shearing effect of fetal head on the urethra during childbirth Cystourethrocele – may occur in nulliparous women ○ Caused by congenital weakness and relaxation Enterocele – herniation of the rectouterine pouch into the rectovaginal septum Vaginal prolapse – vaginal walls herniate through vaginal opening Uterine prolapse – descent of the cervix or entire uterus into the vaginal canal Benign Growths and Proliferative Conditions Benign ovarian cysts – develop from mature ovarian follicles that do not release their ova (follicular cysts) or from a corpus luteum that persists abnormally instead of degenerating (corpus luteum cyst) ○ Unilateral ○ The more solid (less fluid filled) a follicular cyst is the more likely malignancy is ○ Cysts usually regress spontaneously ○ Some corpus luteum cyst are highly vascular – larger cyst can rupture and cause hemorrhage ○ Cysts can cause ovarian torsion Follicular Cysts – dominant follicle fails to rupture, or one or more of the nondominant follicles fail to regress. Corpus Luteum Cysts – formed by the granulosa cells left behind after ovulation; can cause hemorrhage Dermoid Cysts – growths may contain mature tissue, including skin, hair, sebaceous and sweat glands, muscle fibers, cartilage, and bone. Endometrial polyp – benign mass of endometrial tissue. ○ Contains a variable amount of glands, stoma, and blood vessels. ○ Common cause of intermenstrual or excessive menstrual bleeding. ○ Malignancy is rare. Leiomyomas – commonly called uterine fibroids ○ Benign tumors of smooth muscle cells in the myometrium (muscle layer of the uterus) ○ Incidence in women 30-50 ○ Most are small and asymptomatic ○ Cause abnormal uterine bleeding, pain, and symptoms related to pressure on nearby structures Adenomyosis – islands of endometrial glands surrounded by benign endometrial stroma within the myometrium ○ Asymptomatic, or abnormal bleeding, dysmenorrhea, uterine enlargement, and tenderness Endometriosis – presence of functioning endometrial tissue (responds to hormonal stimulation) implants outside the uterus ○ Responds to hormone fluctuations of the menstrual cycle ○ Possible causes: Retrograde menstruation Spread through vascular or lymphatic systems Stimulation of multipotential epithelial cells on reproductive organs Depressed Tc cells tolerate ectopic tissue Genetic predisposition ○ Causes inflammatory reaction at the site of implantation ○ Clinical manifestations can mimic other disease processes such as PID, IBS, ovarian cysts, dysmenorrhea Most commonly infertility and pain, dysmenorrhea, dyschezia, dyspareunia Less common = constipation, abnormal vaginal bleeding Cervical Cancer Risk factors: ○ Infection with high-risk HPV is necessary precursor to developing CIN and cervical cancer ○ HPV vaccination substantially reduces risk ○ Smoking, immunosuppression and poor nutrition are cofactors ○ Multiple sexual partners increases risk Progressively serious neoplastic alterations are: ○ Cervical intraepithelial neoplasia (cervical dysplasia) Replacement of some epithelial cells by atypical , neoplastic cells Staged depending of depth of epithelial involvement ○ Cervical carcinoma in situ Precancerous dysplasia More common in younger women ○ Invasive cervical carcinoma Direct invasion into adjacent tissues; ureters, structures of the lateral pelvic wall, vaginal stroma and epithelium, lower uterine segment and myometrium Vaginal Cancer Arise from epithelium Rare, and most are secondary in nature Risk factors are in utero exposure to DES (non steroidal estrogen) Vulvar Cancer Majority are squamous cell carcinomas Some melanomas, bartholin gland carcinoma, sarcoma, and adenosquamos carcinoma h/o HPV infection is risk factor Endometrial Cancer Most common pelvic region cancer Risk factors = unopposed estrogen exposure, obesity, infertility, failure to ovulate, early menarche or late menopause, and tamoxifen Oral contraceptive use protects against endometrial and ovarian cancers Ovarian Cancer Cause of the most deaths of any other genital cancer in women Risk factors include early menarche, late menopause, nulliparity, use of fertility drugs, and associations with breast cancer susceptibility genes Infertility Inability to conceive after 1 year of unprotected intercourse with the same partner Fertility can be impaired by factors in the man, woman, or both ○ Male factors include; diminished quality and production of sperm ○ Female factors are associated with malfunctions of the fallopian tubes, ovaries, or reproductive hormones Disorders of Male Reproductive System Urethritis – inflammation of the urethra usually, but not always, caused by a sexually transmitted disease ○ Nonsexual origins can be caused by urologic procedures, insertion of foreign objects, anatomic abnormalities, or trauma ○ Symptoms include dysuria, frequency , urgency, urethral tingling or itching, and clear or purulent discharge Urethral strictures – fibrotic narrowing of the urethra caused by scarring which is either acquired or congenital ○ Commonly a result of trauma or untreated or severe urethral infections ○ Primary symptom is diminished force and caliber of the urinary stream; other symptoms include urinary frequency and hesitancy, mild dysuria, double urine stream or spraying, and post voiding dribbling Phimosis – inability to retract foreskin over the glans of the penis (distal to proximal) ○ Caused by poor hygiene or chronic infections ○ Can lead to paraphimosis Paraphimosis – inability to replace or cover the glans with the foreskin (proximal to distal) ○ Can constrict the penile blood vessels, preventing circulation to the glans Peyronie disease – “Bent nail syndrome”; slow development of fibrous plaques (thickening) in the erectile tissue of the corpus cavernosa ○ Fibrosis prevents engorgement on the affected side, causing a lateral curvature of the penis during erection ○ Occurs in middle-aged men and causes painful erections and intercourse Priapism – condition of prolonged painful penile erection, not stimulated by sexual arousal ○ Urologic emergency ○ Corpus cavernosa fills with blood that does not drain out, because of venous obstruction ○ Associated with spinal cord trauma, sickle cell disease, leukemia, and pelvic tumors; can be idiopathic Penile cancer ○ Carcinoma of the penis is rare; mostly squamous cell carcinomas ○ Risk factors include HPV, smoking and consequences of treatment of psoriasis ○ Penile carcinoma in situ involves the glans ○ Invasive carcinoma involves the glans and the shaft ○ 5-year survival rate 50% Balanitis – inflammation of the glans penis ○ Usually associated with foreskin inflammation (posthitis) ○ Accumulation under the foreskin (smegma) causes irritation of the glans ○ Associated with phimosis, skin disorders, and infections Varicocele – inflammation/dilation of veins in the spermatic cord ○ Caused by inadequate or absent valves in the spermatic veins Hydrocele – scrotal swelling caused by collection of fluid within the tunica vaginalis ○ Imbalance between fluid secretion and reabsorption Spermatocele – painless diverticulum of the epididymis located between the head of the epididymis and the testis ○ Contains milky fluid that contains sperm and does not cover the entire anterior scrotal surface Cryptorchidism – congenital condition in which one or both of the testes fail to descend from the abdominal cavity into the scrotum ○ Treated or untreated cryptorchidism is associated with infertility and a significantly increased risk of testicular cancer Orchitis – acute inflammation of the testes ○ Complication of a systemic disease or related to epididymitis ○ Pathogenic organisms may reach the testes by ascending through the vas deferens and epididymis ○ Mumps most common cause ○ Complications include hydrocele and atrophy Torsion of the testes – rotation of the testis ○ The rotation causes the twisting of the blood vessels in the spermatic cord ○ Painful and swollen testis ○ Condition may be spontaneous or follow physical exertion or trauma ○ Surgical emergency; needs to be corrected within 4-6 hours, otherwise necrosis and atrophy of testicular tissues Cancer of the testes ○ Among the most curable of cancers ○ Common in men between ages 15 and 35 ○ Causes painless testicular enlargement ○ Cause is unknown, high androgen levels, genetic predisposition, and a history of cryptorchidism, trauma, or infection may contribute to tumor genesis ○ Most are germ cell tumors Epididymitis – inflammation of the epididymis ○ Common in sexually active young men ○ The pathogenic microorganism reaches the epididymis by ascending the vas deferens from an already infected bladder or urethra Benign prostatic hyperplasia – enlargement of the prostate gland ○ Symptoms associated with urethral compression ○ LUTS symptoms (Lower Urinary Tract Symptoms) Irritative – frequency, urgency, nocturne, and urge incontinence Obstructive – hesitancy or difficulty initiating the stream, straining to void, a reduced flow, intermittent stream or sensation of incomplete emptying ○ Relationship to aging ○ Involves a complex pathophysiology Circulating androgens are associated with BPH and enlargement ;DHT converted testosterone by type II 5-alpha-reducatse and then DHT works locally not systemically Growth-promoting and tissue remodeling microenvironment supported; theses interactions lead to increase in prostate volume Cancer of the prostate ○ Most common cancer in American males; 3rd most common worldwide ○ Prostatic cancer is asymptomatic until its advanced stages ○ Symptoms are similar to BPH ○ Risk factors: Dietary factors – especially if it affects hormone levels High intake of fat, increased calcium intake, low intake of dietary fiber, high intake of protein Hormones – androgen sensitive cancer; anabolic steroid use Vasectomy – by elevating circulating androgens; immunologic mechanisms involving antisperm antibodies, reduction of seminal fluid levels of the active metabolite of testosterone in the prostate Chronic inflammation increases risk Familial factors are involved Prostatitis – inflammation of the prostate Normal protective barriers that protect the lower urogenital tract from infection: ○ Urethral length ○ Micturition ○ Ejaculation ○ Antimicrobials in prostatic fluid (PAF) = prostatic antibacterial factor – most important chemical defense ○ Structural malformations and instrumentation weaken these defenses Similar symptoms to UTI with acute prostatitis Chronic nonbacterial prostatitis more like symptoms of BPH Common bacteria = Enterobacter, E. coli, enterococcus, Klebsiella, and Pseudomonas Acute bacterial – ascending infection of the urinary tract ○ Inflammatory response causes prostate to enlarge, become tender, and firm or boggy ○ Clinical manifestations similar to acute cystitis or pyelonephritis – sudden onset of malaise, low back and perineal pain, high fever, and chills, dysuria, inability to empty bladder, nocturia, and urinary retention. Chronic bacterial – recurrent urinary symptoms and persistence of pathogenic bacteria (usually gram negative) in urine or prostatic fluid ○ Most common recurrent UTI in men ○ Frequency, urgency, dysuria, perineal discomfort, low back pain, and sexual dysfunction ○ Prostate only slightly enlarged or boggy ○ Fibrosis caused by repeated infections lead to it to become firm and irregular in shape Nonbacterial – most common, prostatic inflammation without evidence of bacterial infection ○ Prostadynia is pain in the prostate. Considered type of nonbacterial ○ Thought to be caused by reflux of sterile urine into the ejaculatory ducts as a result of high-pressure voiding Benign Breast Lesions Nonproliferative breast lesions ○ Used to discriminate from the proliferative changes commonly associated with increased risk for breast cancer ○ Fibrocystic changes (FCC) – physiologic nodularity and breast tenderness that wax and wane with the menstrual cycle ○ Cysts – fluid filled sacs; type of lump that commonly occurs in women 30-50s Proliferative breast lesions without atypia: ○ Characterized by proliferation of ductal epithelium and/or stroma without cellular signs of malignancy ○ Types: Epithelial hyperplasia Florid hyperplasia Sclerosing adenosis Complex sclerosing lesion Papillomas Proliferative breast lesions with atypia: ○ Some abnormal structure or atypia ○ Atypical hyperplasia (AH) Increase in the number of cells with some variation in cellular structure Studies show 4x increase risk of breast cancer in those women with AH ○ Ductal hyperplasia (ADH) Increased number of cells mostly within the lumen of the terminal ducts Includes continuum of changes – cell structure and placement- ranging from an increase in cellularity to features of ductal carcinoma in situ Cells do not completely fill ductal spaces as compared to DCIS ○ Lobar hyperplasia Proliferation of small, uniform cells in the lumen of lobular units Atypical lobular hyperplasia (ALH) and lobular carcinoma in situ are identical but the cells in ALH do not distend more than 50% within the lobule ALH can extend into the ducts and is associated with increased risk of invasive carcinomas Breast Cancer Reproductive factors ○ Pregnancy ○ Young age of at 1st pregnancy decrease lifetime risk ○ Increasing parity associated with long-term reduction ○ Lobular involution – parenchymal elements progressively atrophy and disappear ○ Lobular involution is associated with reduced risk of breast cancer ○ Researchers proposed that delayed involution (persistent grandular epithelium) is a major risk factor for breast cancer Hormonal factors ○ Vast majority of breast cancers are hormone dependent initially ○ Estrogen- receptor positive and/or progesterone-receptor positive ○ Estrogen normally important in cellular proliferation, differentiation, and apoptosis ○ Carcinogenicity of estrogens involves ○ Receptor-mediated hormonal activity shown to stimulate cellular proliferation resulting in increased opportunities for accumulation of genetic damage ○ Oxidative catabolism of estrogens mediated by various cytochrome P-450 complexes that eventually activate and generate reactive oxygen species that can cause oxidative stress and genomic damage directly ○ Estrogens function as inducers of aneuploidy (gain or loss of chromosomes) Environmental factors and lifestyle ○ Radiation ○ Diet – only statistically significant factor is alcohol intake, being overweight, and weight gain after menopause ○ Chemicals (xenoestrogens) – synthetic chemicals that mimic the actions of estrogens and are found in many pesticides, fuels, plastics, detergents, and drugs ○ PCBs, pesticides, BPA, tobacco smoke, metals, food additives, HRT ○ Physical activity – regular physical activity may decrease risk ○ Familial factors and tumor-related genes – first degree relatives increases a woman's risk 2-3 times; increasing if 2 first-degree relatives are involved especially if the disease occurred before menopause and was bilateral Mainly BRCA 1 and BRCA 2 – autosomal dominant transmission Also CHEK2 (Li-Fraumenia syndrome), ataxia telangiectasia (AT), and STK11 (Peutz-Jeghers syndrome Ductal carcinoma insitu (DCIS) – malignant heterogeneous group of lesions limited to ducts and lobules Invasive breast carcinoma – malignant invasive epithelial lesion derived from the terminal duct lobular unit ○ Can arise anywhere in the breast parenchyma or accessory breast tissue; most common in upper outer quadrant ○ Exact molecular events leading to invasion are complex and not completely understood Male breast cancer – most commonly seen after age 60, generally uncommon but incidence is increasing ○ Tumors resemble carcinomas of the breast in women ○ Most are ER+ (estrogen receptor positive) ○ Crusting and nipple discharge are common clinical manifestations ○ ○ Poor prognosis because men delay treatment Risk factors: Gynecomastia Radiation of the chest wall Germline mutations in BRCA 1 and BRCA 2 FH of breast cancer Klinefelter syndrome Testicular disorders Obesity Sexually Transmitted Infections – general term for any disease that can be spread by intimate and/or sexual contact Bacterial STIs ○ Gonorrhea – Neisseria gonorrhoeae Complications include PID; sterility; and disseminated infection, which is spread from the bloodstream to the skin, joints, and heart Passed from mother to fetus typically manifests as an eye infection and develops 1-12 days after birth Common sites: Endocervical canal (inner portion of the cervix) – most common site for women Urethra Skene and/or Bartholin glands Urethra or rectum – most common site for men Clinical manifestations: Men – sudden onset of painful urination or purulent penile discharge, or both Women – asymptomatic, dysuria, increased vaginal discharge, increased flow or dysmenorrhea, dyspareunia, lower abdominal and/or pelvic pain, fever; mucopurulent discharge from the cervical os Disseminated gonococcal infection (DGI) – rare systemic complication brought about by the spread of infection through the bloodstream; life-threatening condition causing a generalized rash and severe joint pain Perihepatitis – spread of N. gonorrhoeae to the liver Ophthalmia neonatorum – gonococcal eye infection in an infant from an infected mother ○ Syphilis – Treponema pallidum Higher incidence among men who have sex with men; in urban and poverty-stricken areas and prison population Transmitted most often during first few years of infection – most transmissible in the primary and secondary stages of the disease Can be transmitted to fetus during pregnancy – maternal-fetal transmission can occur as early as 9 weeks’ gestation Congenital syphilis contributes to prematurity of the newborn with bone marrow depression, CNS involvement, renal failure, and intrauterine growth retardation Primary syphilis: Local manifestations – 12 days to 12 weeks after exposure; avg: 3 weeks Granulomatous tissue reaction – hard chancre at site of infection (eroded, painless, firm, and indurated [hard] ulcer) Firm, enlarged, and nontender regional lymph nodes accompany chancres Microorganisms drain with the lymphatic fluid Secondary syphilis: Systemic manifestations – 6 weeks after appearance of hard chancre Fever, malaise, sore throat, hoarseness, anorexia, joint pain, skin rash, and lesions (condylomata lata) Latent syphilis – as short as 1 year or as long as a lifetime; medical evidence of the infection, asymptomatic individual Tertiary syphilis – appearing after latent phase Usually asymptomatic yet most severe stage Destructive systemic manifestations Formation of gummas: Destructive skin, bone, and soft-tissue lesions Within the CV system infection may cause aneurysms, heart valve insufficiencies, and heart failure Within the CNS infection in the CSF may cause neurosyphilis ○ Chancroid – Haemophilus ducreyi Painful, tender, soft chancre Women: Asymptomatic but can have dysuria, dyspareunia, vaginal discharge, pain on defecation, or rectal bleeding Men: Unilateral, painful genital ulcers, local lymphadenopathy, inguinal buboes ○ Granuloma inguinale – Klebsiella granulomatis Mildly contagious; repeated exposure required Concurrent infection with syphilis is common Very rare in the United States; more prevalent in India, New Guinea, Africa, and central Australia Donovan bodies – bacteria-filled vacuoles within white cells Symptoms – painful nodule with itching, ulcers on penis or labia ○ Bacterial vaginosis – Gardnerella vaginalis Sexually associated condition, but not always an STI Characterized by increased, thin, gray-white vaginal discharge with a strong “fishy” odor ○ Chlamydia – Chlamydia trachomatis Most common STI in the United States Untreated or undertreated chlamydial infections are the primary cause of preventable infertility and ectopic pregnancy Leading cause of blindness worldwide – passes from infected mother to the eyes of newborn infants during birth Transmitted by oral, anal, or vaginal intercourse; mother-to-child transmission during vaginal delivery Manifestations: Men – clear, mucous discharge or mild burning with urination Women – leading cause of tubal infertility; acute urethral syndrome (dysuria, urinary frequency, and presence of sterile pus in the urine); yellow mucopurulent discharge with cervicitis Newborn – conjunctivitis and pneumonia Viral STIs ○ Human Papillomavirus (HPV) Most common viral STI in United States Associated with cervical and vulvar cancer in females and anorectal and squamous cell carcinoma of the penis in men High-risk strains of HPV (HR-HPV) do not cause genital warts Infants can be infected during delivery Clinical manifestations Condylomata acuminata (genital warts) Soft, skin-colored, whitish pink–to–reddish brown benign cauliflower painless growths ○ Genital Herpes Two serotypes – genital lesions can be caused by either Herpes simplex virus type 1 Herpes simplex virus type 2 Can remain in latent stage until reactivated; cause of reactivation unknown but may be related to stress, sun exposure, hormonal fluctuations, or illness Clinical manifestations: First-episode primary genital infection – no antibodies, small vesicular lesions with fever and malaise First-episode non primary HSV – pre existing antibodies, systemic symptoms fewer Recurrent infections – mild local symptoms Newborn – local infection of eyes, skin, or mucous membranes to severe disseminated infection with CNS involvement ○ Molluscum contagiosum Benign infection of the skin that infects the face, hands, lower abdomen, and genitalia Taken into epithelial cells by phagocytosis; replicates to produce molluscous bodies Lesions often spontaneously heal after several months but are contagious until completely healed Parasitic Infections ○ Scabies – Sarcoptes scabiei Has lifespan of 30 days; once deposited on human skin, it burrows through the horny layer of the stratum granulosum Transmission of scabies requires prolonged, close skin-to-skin contact ○ Trichomoniasis – T. vaginalis Common cause of lower genital tract infection; found in both partners; urethra most common site of infection in men, primarily involves vagina in women Clinical Manifestations – range from none to severe, including pain on intercourse, dysuria, copious frothy malodorous vaginal discharge, and internal pruritus; rarely small, punctuate red marks called strawberry spots are visible; most men remain asymptomatic; possible clinical manifestations include scant intermittent discharge, slight pruritus, and mild dysuria ○ Pediculosis Pubis “crabs” – Phthirus pubis Transmission – intimate sexual contact or contact with infected bed linens or clothing Clinical manifestations – mild-to-severe itching, allergic sensitization, and secondary infections from scratching

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