14 1 Inflammation

Inflammation of the Female Reproductive Tract

Self-cleansing (lactobacillus) Mucus

1. Vulvitis ( 外阴炎 ) Bartholinitis/Bartholin’s cyst ( 前庭大腺炎／前庭大腺囊肿 ) 2. Vaginitis ( 阴道炎 ) 3. Cervicitis ( 宫颈管炎 ) 4. Pelvic inflammatory disease (PID) ( 盆腔炎 )  Genital tuberculosis ( 生殖器结核 )  Sexually transmitted diseases (STD) ( 性传 播疾病 )

Inflammed, Congestion

Vulvitis ( 外阴炎 )

Clinical Manifestation Vulvar pruritus ( 瘙痒 ) Pain Burning sensation Congestion ( 充血 ) Swelling 肿胀 Eczema ( 湿疹 ) Profuse frothy greenish

Etiology Specific organisms or non-infective dermatitis ( 皮炎 ) • Irritation from vaginal discharge ( 分泌物 ) or menses • Lack of vulvar hygiene • Glycouria

Treatment • Keep the vulva clean and dry • Remove the cause • 1/5000 KMnSO4 (potassium permanganate, PP) solution bath • Antibiotics ointment

Bartholinitis ( 前庭大腺炎 ) Infection of the major vestibular glands ( 前庭大腺 ) (Bartholin’s glands) ( 巴氏腺 )

Bartholin’s Cyst ( 前庭大腺囊肿 )

Major vestibular glands (Bartholin’s glands)

Bartholinitis （前庭大腺炎） Etiology Staphylococcus, E.coli, streptococcus, enterococcus, gonococcus, and polymicrobial infection is common. Clinical manifestation Symptoms of a local infection Abscess of Bartholin gland: a painful red swelling Treatment Antibiotics (Ampicillin) in the early stage Drain the abscess (excision of an elliptical piece of skin)

Bartholin’s Cyst ( 前庭大腺囊肿 )

• Marsupialization ( 造口术 ) for preservation of the gland function • Excision for recurrent cases

Vaginitis • • ) • • •

Trichomonal vaginitis ( 滴虫性阴道炎 ) Candidal Vulvovaginitis ( 假丝酵母菌性外阴阴道炎 Bacterial Vaginosis (BV) ( 细菌性阴道病 ) Senile vaginitis ( 老年性阴道炎 ) Infantile vulvovaginitis ( 婴幼儿外阴阴道炎 )

Trichomonal Vaginitis 滴虫性阴道炎 (Trichomoniasis)

Etiology Trichomonad ( 毛滴虫 ) ： A flagellate protozoan ( 有鞭毛原虫 ) Best living environment : Moist, anaerobic 厌 氧的 , pH value: 5.2-6.6, 25℃-42 ℃

滴虫性阴道 炎 (trichomonal vaginitis)

• 一种由 阴道毛 滴虫 引起的 常见的 阴道 炎。

临床表现 典型

Typical symtom

症状 稀薄 的泡沫 状白 带增多 persistent discharge+ 外阴 瘙痒 pruritus vulvae

正常图像 虫图像

滴

Transmission 传播 1. Sexual contact (70% male infection, asymptomatic 无症状的 carrier) 2. Nonsexual transmission (iatrogenic 医源性的 )

Pathogenesis • The trichomonad lives on glycogen and iron of the host cell • Direct contact and damage of the target cell • Induction of immune reaction resulting in inflammation

Clinical Picture

Latent period 潜伏期 : 4-28 days Asymptomatic: 25-50% Symptoms ： Main: Profuse 大量的 vaginal discharge and pruritus Occasional: odor, pain, dyspareunia , dysuria 排尿困难 infertility （ sperm ）

Characteristics of the vaginal discharge Copious ( 大量的 ) , Purulent ( 脓性的 ), Gray to yellow color, Malodorous ( 恶臭的 ), Frothy ( 起泡沫的 ) Strawberry cervix: Tiny, punctate hemorrhages ( 点状出血 ) grossly visible on the mucosa

滴虫的“草莓状宫颈 strawberry cervix”

Tiny, punctate hemorrhages ( 点状出 血 )

Diagnosis 1. Microscopic (wet mount 湿涂 片 ) identification of the trichomonad (sensitivity: 60%-70%) 2. Precautions for the examination Avoid : intercourse 1-2 days before examination washing and medication lubricant 润滑剂 heat preservation 3. Culture for suspected 可疑 cases 4. PCR (Polymerase chain reaction)

Treatment (1) 1. Systemic therapy (First choice,90-95% effective) Oral metronidazole ( 甲硝唑，灭滴灵） a) 2g single dose b) 400mg, twice or 3 times a day, for 7 days. 2. Topical application 局部 应用 (≤50%effective) a) Effervescent tablets ( 泡腾片 )of metronidazole 200mg/day, 7-10 days b) Metronidazole gel c) Acidification 酸化 of vagina with 1% lactic acid or 0.5% acetic acid 醋酸

Treatment (2) Criterion for cure: Negative finding in postmenstrual examination of the vaginal discharge for three times Failure rate: 5%-10% Poor compliance 顺从性 Repeated infection To avoid repeated infection: Sterilization 杀菌 of underwear, towels 毛巾 , etc Treatment of the sexual partner Metronidazole is still effective in recurrent cases.

Candidal Vulvovaginitis 假丝酵母菌性外阴阴道炎 (Vulvovaginal Candidiasis)

Etiology 1. Very common a) About 1/3 of vaginitis cases are caused by fungal 霉菌 infection. b) About 75% of women develop candidiasis at least once in life. 2. The etiologic agent is Candida ( 假丝酵母菌 / 念珠 菌 ). Candida albicans ( 白假丝酵母菌 ) is responsible for 80-90% of vulvovaginal candidiasis.

3. Candida albicans is an opportunistic pathogen 条件致病菌 1) Suitable environment: acidic ( ＜ 4.5), warm, and moist 2) Candida albicans can be isolated from 10-20% nonpregnant and 30% pregnant asymptomatic women.

Treatment is not indicated unless symptoms are present.

Predisposing factors 易感 因素 1. Pregnancy 2. Diabetes mellitus 3. Immunosuppressants 免疫抑制剂 4. Broad-spectrum antibiotics suppressing the vaginal normal flora 菌丛 (esp. lactobacillus) 5. Others: restrictive synthetic underwear, obesity, contraceptive medication

Transmission 1) Endogenous infection (most often) vagina, oral cavity, intestinal tract 2) Sexual contact 3) Contacting fomites ( 污染物 )

Pathogenesis

Two phases of candida albicans 1) Yeast 酵母 spores ( 芽孢相 ): Asymptomatic parasitism 2) Pseudohyphae ( 菌丝相 ): Pathogenic 3) Mechanism: a) Candida at the pseudohypha phase penetrate vaginal epithelium for nutrients b) Growing candida albicans release proteolytic 蛋白水 enzymes and toxins etc. resulting in inflammation reaction

Clinical Picture 1. Vulvovaginal pruritus (main) usually intense, coincident with menses or intercourse 2. Increased vaginal discharge The classic finding is white, thick,curd-like 凝乳状的 discharge forming patches 斑 adherent to the vaginal walls.

Diagnosis 1. Wet mount microscopic identification of candida albicans in the discharge Saline: 30-50% 10% KOH: 70-80% 2. Gram’s stain 革兰氏染色 : 80% 3. Culture: higher sensitivity and drug test 4. Measurement of pH value may be useful for discovering cases of complicated infection (4.0-4.7). a pH<4.5 simple infection a pH>4.5 combined infection

临床表现

典型症 状 • 白色稠厚豆渣样 白带增多 • + • 外阴剧烈瘙痒

霉菌性阴道炎 TCT 图像 Yeast spores

Pseudohyphae

Treatment 1. Elimination 除去 of predisposing factors 2. Topical application of antifungal agents 抗真菌剂 Vaginal suppositories ( 栓剂 ) ： 1) Miconazole ( 咪康唑 / 达克宁 ) a) 200mg/day for 7days b) 400mg/day for 3 days 2) Clotrimazole ( 克霉唑 ) a) 150mg/day for 7 days b) 150mg, twice a day for 3 days c) 500mg single dose

3) Nystatin ( 制霉菌素 / 米可定 ) 100,000units/day for 10-14 days 4) Methyl violet ( 龙胆紫 ) 0.5-1% , 3-4 times/week for 2 weeks.

3. Systemic medication Oral agents are used only for cases that can not be treated with topical application of antifungal drugs. 8) Fluconazole ( 氟康唑 / 大扶康 ) 150mg, single use. 2) Itraconazole ( 伊曲康唑 / 斯皮仁诺 ) a) 200mg/day for 3-5 days b) 400mg for 1 day divided in two doses

3) Ketoconazole ( 酮康唑 ) 200mg, once or twice/day until culture result is negative Hepatotoxicity may occur. Points of note for treating VVC • Treatment should be followed-up with a premenstrual examination of the vaginal discharge. • Approximately 10% of cases will not respond to initial therapy. • Prolongation of treatment up to 14 days may cure some patients. • Identification and elimination of predisposing factors is important. • Recurrent VVC should be treated with oral therapy followed by prophylactic doses.

Treatment of sexual partner? No treatment for asymptomatics. 15% should be treated

Bacterial Vaginosis 细菌性阴道病

Etiology 1. Imbalance of normal vaginal flora Diminution 减少 of Doderlein lactobacillus and increase in other bacteria, in particular, anaerobic bacteria. 2. Causative factors of the imbalance are unknown Gardnerella vaginalis ( 加德纳菌 )

Clinical Picture Symptoms: 1. 10-40% asymptomatic 2. Mild pruritus or burning sensation 3. Increased vaginal discharge and fishy odor

Signs: Discharge: thin, greyish-white, homogenous, but not sticky No inflammation reaction (No epithelial edema 水肿 or erythema 红斑 )

Diagnosis Identification of clue cells *(wet mount in saline) together with 3 of the following 4 items 1. Vaginal discharge: homogenous, thin and white 2. pH>4.5: in virtually all cases, usu. 5.0-5.5 3. Positive Whiff test (with 10% KOH) 4. Clue cells * Clue cells are desquamated 脱屑的 epithelial cells covered with clumps 丛，簇 of coccobacili 球杆 菌 esp. Gardnerella vaginalis ( 加德纳菌 ), which gives the cells a speckled ( 有小斑点 ) appearance.

Whiff test Ammonia odor

诊 •

1. Vaginal discharge: homogenous, thin and white fishy odor

•

2. pH>4.5: in virtually all cases, usu. 5.0-5.5

•

3. Positive Whiff test (with 10% KOH) 胺臭 味试 验阳性

•

4. Clue cells 线索 细胞阳

性

断

细菌 性阴 道病 索细胞

线

Treatment (1) 1. Systemic therapy (oral) (80%) 1) Metronidazole 400mg, 2-3 times a day for 7 days 2) Clindamycin ( 克林霉素 / 氯林霉素 / 氯洁霉 素) 300mg, twice a day for 7 days 2. Topical therapy (80%) 1) Effervescent tablets of metronidazole 200mg/day, for 7-10 days 2) 2% Clindamycin cream, once a day for 7 days 3. Vaginal washing 1-3% H2O2 , 1% lactic acid, 0.5% acetic acid

Treatment (2) 1. Systemic or topical treatment has the same cure rate (80%). 2. Patients who are asymptomatic, but scheduled to have a gynecologic surgical procedure should be treated. 3. Patients who are pregnant can be treated with oral metronidazole. 4. Follow-up examination should be given 1-2 and 3-4 weeks (postmenstrual) after the treatment. Criteria for cure: Absence of clue cells with at least 1 of the following items: a) Normal vaginal discharge b) pH≤4.5 c) Whiff test negative

Other forms of vulvovaginitis 1. Senile vaginitis ( 老年性阴道炎 ) Atrophic vaginitis( 萎缩性阴道炎 ) • Infantile vulvovaginitis ( 婴幼儿外阴阴道炎 )

Differential Diagnosis of vaginitis Bacterial Vaginosis Candidiasis

Trichomoniasis

Complaints

discharge↑m ild pruritus

severe pruritus discharge↑ burning mild pruritus

Vaginal discharge

white homogenous fishy

white curd-like

thin purulent frothy

normal

edema erythema

punctate hemorrhage

＞ 4.5 (4.7-5.7)

＜ 4.5

＞ 5 (5.66.5)

Vaginal epithelium ＋ Vaginal pH Whiff test Microscopic

－ Clue cells WBC rare

Candida WBC some

Trichomonad WBC many

Inflammation of the Cervix 1. Common: 50% women of reproductive age 2. May lead to pelvic infection 3. Need to identify a venereal disease and differentiate from malignancies

Cervicitis: Vaginal portion of the cervix (Ectocervix 宫颈阴道 Mucosa of the cervical canal (Endocervix 宫颈内

Acute Cervicitis

Etiology 2. Neisseria gonorrhoeae ( 淋病奈瑟菌 ) Chlamydia trachomatis ( 沙眼衣原体 ) causing superficial infection of the cervical columnar mucosa

2. Staphylococcus ( 葡萄球菌 ) Streptococcus ( 链球菌 ) Enterococcus ( 肠球菌 ) causing infection after an abortion, puerperium 产褥期 , cervical injury, foreign bodies

Clinical Picture Symptoms 1. Asymptomatic 2. Mucopurulent 粘液脓性的 vaginal discharge Vaginal irritation symptoms:pruritus, burning sensation Lumbosacral 腰骶部 pain, Intermenstrual bleeding, postcoital bleeding Symptoms of the lower urinary tract Signs Inflammation of the cervix with mucopurulent discharge (MPC for mucopurulent cervicitis)

Diagnosis 1. Gram’s stain of the cervical discharge for leukocyte ≥30/HP or ≥10/×1,000 2. Tests for gonococcus 淋球菌 and chlamydia 衣原体 3. Wet mount microscopy for trichomonads 毛滴虫

Management

ystemic medication hoice of drugs depends on the pathogens. xamples: Gonorrhea infection ： Third generation Cephalosporins Ceftriaxone Sodium ( 头孢曲松钠 / 头孢三嗪 / 菌必治 / 罗氏芬 Spectinomycin ( 大观霉素 / 壮观霉素 / 淋必治 ) hlamydia trachomatis Doxycycline ( 多西环素 ) Azithromycin ( 阿奇霉素 ) Erythromycin ( 红霉素 ) Ofloxacin ( 氧氟沙星 )

Chronic Inflammation of the Cervix

细胞 学检 查

治疗前常规检查

治疗

Cervical Erosion Etiology 3. When the stratified epithelium ( 复层上皮 ) which normally covers the vaginal portion of the cervix is replaced by columnar epithelium which is continuous with that of the cervical canal. 2. Most erosion are not infected, nor they are the result of inflammation. 3. Occurs in the newborns, pregnancy, oral contraceptives

Clinical Features Symptoms The only symptom is a mucoid discharge. A slight postcoital bleeding (but malignancy should be excluded)

Signs A red area is seen around the external os.

Classification Depends on the depth and area of the lesion Types: simple, granular, papillary Grades: I ( ＜ 1/3), II (1/3-2/3), III ( ＞ 2/3)

Treatment • Erosion found on routine examination should not be treated unless it is causing troublesome discharge. • A cervical smear is needed before the treatment, and if necessary, colposcopy ( 阴道镜 ) and biopsy. • Cervical ectropion ( 宫颈外翻 ) Physical therapy Thermal cauterization, Cryotherapy, Laser therapy

Cervical Polyps Small pedunculated neoplasms of the cervix • Endocervical polyp: Originating from the endocervix • Ectocervical polyp: Originating from the vaginal portion

Pathology Gross appearance: Endocervical polyp: Red or pink, rounded or tongue-like Ectocervical polyp: Pale, flesh-colored, smooth, rounded with a broad pedicle Microscopic: Vascular connective tissue stroma covered with columnar or squamous epithelium or both. Congestion, edema or leukocytein filtration may be present.

Clinical Features Some are asymptomatic. Slight postcoital bleeding

Treatment Cervical polyp should be treated. • Malignant change (<1%) • Polypoid cervical cancer Twisting off a polyp without an anesthetic and cauterizing the base. Recurrent cases are treated with canal dilation and cauterization of the stalk.

Chronic Endocervicitis ( 宫颈粘膜炎 ) (Infection) Etiology Pathogens: Normal cervical and vaginal flora

Pathology • Thickened endocervix that produces a whitish pus • A cervical os surrounded by a reddish area • Hypertrophy of the lacerated cervix

Clinical Features 1. Persistent leukohrrea usu. mucopurulent 2. Slight postcoital staining 3. Pains lower abdominal discomfort, lumbosacral backache, dysmenorrhea, dyspareunia 4. Infertility 5. Urinary symptoms frequency, urgency, dysuria due to subvesical lymphangitis not to cystitis

Diagnosis • The characteristic discharge from external os of the cervix. • Cytologic and colposcopic studies are helpful, but only biopsy is definitive. • Cultures are not so helpful.

Treatment Even if chronic endocervicitis is asymptomatic, it should be treated. 1. Medical treatment Systemic rather than topical Based on culture and sensitivity test 2. Surgical treatment A note of caution: postoperative bleeding, infection, stricture formation, infertility. Methods: thermal therapy, cryotherapy, laser therapy conization, hysterectomy.

Nabothian Cysts Retention cysts of the cervical glands caused by obstruction of the gland orifices by the growth of squamous epithelium. The cysts may be infected and contain pus.

Cervical Hypertrophy

Pelvic Inflammatory Disease (PID) Infection of the upper genital tract Terms: Endometritis ( 子宫内膜炎 ) Salpingitis ( 输卵管炎 ) Oophoritis ( 卵巢炎 ) Myometritis ( 子宫肌炎 ) Pyosalpinx ( 输卵管积脓 ) Hydrosalpinx ( 输卵管积水 ) Peritonitis ( 腹膜炎 ) Tubal ovarian abscess (TOA) ( 输卵管卵巢脓肿 )

Epidemiology Sexual activity A disease of sexually active, menstruating women. Acute PID occurs in 1-2% of young sexually active women annually. Age The peak incidence occurs in their late teens and early twenties. The most common serious infection in women of 16-25 years of age

Contraceptive practices Contraceptive methods

No.of PID/woman-years

Sexually active, using no contraception: 3.42 Oral contraceptives:

0.91

Barrier methods

1.39

Intrauterine devices (IUD)

5.21

Financial cost In USA, $3.5 billion annually in 1990s Medical sequelae Ectopic pregnancy: 6-10 fold increase PID accounts for 50% Chronic pain: 4 fold increase Infertility: acute PID account for 5-60% of cases Tubal obstruction: 11.4%, 23.1%,54.3% from 1, 2, 3 episodes of infection Mortality: septic shock and death

Etiology Pathogens that are sexually transmitted 1) Neisseria gonorrhoeae: in USA, 40-50% cases of PID 2) Chlamydia trachomatis: in USA, 10-40% cases of PID The two pathogens may account for 2/3 of the PID 3) Mycoplasma ( 支原体 ) Recovered from the pus in 2-20% cases of salpingitis Endogenous bacteria 1) Aerobic: streptococci, staphylococci, Escherichia coli 2) Anaerobic: Bacteroides fragilis ( 脆弱类杆菌 ), peptococcus ( 消化球菌 ) ， peptostreptococcus ( 消化链球菌 )

Spreading Route of Infection 1. Ascending along the reproductive tract For non-pregnant and non-puerperal women Gonococcus, C. trachomatis, staphylococcus 2. Lymphatic vessels In puerperal infection, post-abortion infection and IUD associated infection Streptococcus, E.coli, anaerobic bacteria 3. Blood vessels Tuberculosis 4. Direct spreading Infection from other visceral organs.

Acute PID

Predisposing Factors 1. Intrauterine manipulation e.g. artificial abortion , IUD, etc. 2. Infection in the lower reproductive tract, esp. STD 3. Sexual activity 4. Bad hygiene 4. Direct spreading from adjacent viscera 6. Acute onset of a chronic PID

Pathology 1. Acute endometritis and myometritis 2. Acute salpingitis, pyosalpinx and tubo-ovarian abscess (TOA) 3. Acute pelvic peritonitis 4. Acute inflammation of the peritoneal connective tissue (parametritis)( 宫旁结缔组织炎 ) 5. Septicemia ( 败血症 ) and pyemia ( 脓毒血症 ) 6. Fitz-Hugh-Curtis syndrome

Fitz-Hugh-Curtis syndrome Perihepatitis: inflammation of Glisson’s capsule without involvement of the liver parenchyma. Suppurative ( 脓性 ) and fibrous exudation of the capsule occurs causing adhesion between the capsule and the anterior peritoneum. • It happens in 5-10% cases of salpingitis. • It is caused by gonococcus or Chlamydia trachomatis. • Edema and adhesion of the capsule may lead to pain in the upper abdominal region.

Clinical Features Symptoms Vary depending on severity and extent of the infection and types of pathogens Most common: lower abdominal pain, fever, increase in vaginal discharge. Gonorrhea/Chlamydia Trichomatis Signs Variable Typical: Bimanual examination:

Diagnosis Criteria for the diagnosis of PID Minimum: 4) Pain on compression of uterine body or the adnexal region 2) Tenderness of the cervix Specific: 1) Biopsy of the endometrium showing endometritis 2) Ultrasound/MRI identification of liquid-filled enlarged oviducts or TOA 3) Laparoscopic examination Additional:

Differential Diagnosis Appendicitis Rupture or abortion of tubal pregnancy Torsion or rupture of an ovarian tumor

Treatment (1)

1. Systemic medication (Ideal) Based on drug sensitivity test (Empirical) Combination use of drugs Patient’s condition and possible pathogens 1) Oral: Ofloxacin ( 氧氟沙星 ) Metronidazole for 14 days 2) Intravenous: Penicillin or Erythromycin ( 红霉素 ) Gentamycin ( 庆大霉素 ) or Amikacin ( 阿米卡星 / 丁胺卡那霉 素) Metronidazole for endogenous bacteria 3) Cefuroxime sodium ( 头孢呋辛钠 / 西力欣 ) for gonococcus 4) Doxycycline ( 多西环素 / 强力霉素 ) or Azithromycin ( 阿奇霉 素) for chlamydia or mycoplasma

Treatment (2) 2. Surgical treatment for TOA or peritoneal abscesses that can not be controlled by drugs (2-3 days) Indications: 1) Failure of drug therapy 2) Persistent existence of abscesses (2-3 weeks) 3) Rupture of the abscess 3. Traditional Chinese medicine

Chronic PID

Etiology 1. Incomplete treatment of the acute PID 2. Infection from certain pathogens such as Chlamydia trachomatis 3. Residual lesions from previous acute PID Characteristics of chronic PID: 1. Persistence of the condition 2. Difficult to identify the pathogens

Pathology 1. Chronic endometritis 2. Chronic salpingitis and hydrosalpinx 3. Salpingo-oophoritis and tubo-ovarian cyst 4. Chronic inflammation of pelvic connective tissue

Clinical Features 1. Chronic pelvic pain 2. Infertility (20-30%) and ectopic pregnancy 3. Abnormal menstrual cycle 4. Systemic symptoms 5. Signs

Diagnosis Based on history of acute PID, symptoms and signs Differential diagnosis Pelvic congestion or varicosity ( 静脉曲张 ) Endometriosis Tumors Ultrasound and laparoscopic examination is helpful

Treatment According to place of the lesion and the patient’s complaint Usu. comprehensive treatment is required. 1. Physical 2. Traditional Chinese medicine ( 赤丹丸 ) 3. Antibiotics ( 抗炎 II 号栓 ) 4. Drugs that dissolve and absorb inflammatory lesions 5. Surgical treatment