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Pelvic Inflammatory Disease (PID) - 20 Marks

Definition

• Harrison's Principles of Internal Medicine 22E, 2025

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Etiology

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Epidemiology and Risk Factors

• Endocervical infection (gonorrhoea/chlamydia) or bacterial vaginosis (BV)
• History of prior PID (strongest predictor of recurrence)
• Recent IUD insertion (within 1 month)
• Multiple sexual partners; history of STIs
• Frequent vaginal douching
• Recent invasive uterine procedures (D&C, termination of pregnancy, hysterosalpingography)
• Onset during or just after menstruation
• Young age / adolescence

• Oral contraceptive pill use (decreases symptomatic PID)
• Tubal sterilisation (prevents intraluminal spread)

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Pathogenesis

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Clinical Features

Symptoms

• Lower abdominal/pelvic pain - bilateral, dull/aching, of <3 weeks duration
• Abnormal vaginal discharge - yellow or malodorous (mucopurulent cervicitis, MPC)
• Abnormal uterine bleeding (precedes or coincides with pain in ~40%)
• Dysuria (urethral involvement, ~20%)
• Nausea, vomiting, fever if peritonitis develops
• Right upper quadrant (RUQ) pain in 3-10% = Fitz-Hugh-Curtis syndrome (perihepatitis)

Signs

• Cervical motion tenderness (CMT) - pathognomonic clinical sign
• Uterine tenderness (endometritis)
• Adnexal tenderness - usually bilateral
• Adnexal swelling/mass in ~50%
• Fever >38°C in only ~1/3 of patients
• Speculum: MPC (yellow discharge, easily-induced endocervical bleeding)

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Diagnosis

CDC Minimum Criteria (any ONE of the following in a sexually active woman with pelvic pain):

1. Cervical motion tenderness, OR
2. Uterine tenderness, OR
3. Adnexal tenderness

"Treatment appropriate for PID must not be withheld from patients with an equivocal diagnosis - it is better to err on the side of overdiagnosis and overtreatment." - Harrison's 22E

Additional criteria (increase specificity):

• Temperature >38°C
• Elevated ESR (>15 mm/h) or CRP
• Elevated WBC count
• Palpable adnexal mass
• Laboratory confirmation of N. gonorrhoeae or C. trachomatis (NAAT)
• Evidence of MPC on speculum exam
• PMNs outnumbering epithelial cells on vaginal wet prep

Investigations

• NAAT of endocervical/vaginal swab for N. gonorrhoeae and C. trachomatis
• Wet preparation: PMNs in vaginal fluid
• Gram stain: PMNs and gram-negative diplococci
• ESR, CRP, CBC (leucocytosis in up to 60%)
• Urine beta-hCG (to exclude ectopic pregnancy)
• Pelvic USS: identifies TOA, free fluid, tubal thickening - first-line imaging
• MRI: more sensitive - shows increased tubal diameter, intratubal fluid, tubal wall thickening
• CT pelvis (contrast-enhanced): endometrial enhancement, bilateral tubal thickening >5mm, pelvic fat stranding
• HIV screening for all women with PID

Differential Diagnosis

• Ectopic pregnancy (must exclude first with beta-hCG)
• Appendicitis (favoured by anorexia/vomiting early, onset after day 14, unilateral RIF pain)
• Endometriosis
• Ovarian cyst/torsion
• Corpus luteum haematoma

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Imaging in PID

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Treatment

Indications for Hospitalisation (Parenteral Therapy)

1. Diagnosis uncertain - cannot exclude surgical emergency (appendicitis, ectopic)
2. Pregnancy
3. Suspected pelvic abscess (TOA)
4. Severe illness / nausea and vomiting precluding oral therapy
5. HIV infection
6. Patient unable to tolerate or comply with outpatient regimen
7. Failure to respond to outpatient therapy within 72 hours

CDC Recommended Regimens (from Harrison's 22E / CDC MMWR 2021):

• Ceftriaxone 500 mg IM single dose PLUS
• Doxycycline 100 mg PO twice daily x 14 days PLUS
• Metronidazole 500 mg PO twice daily x 14 days

• Parenteral therapy continued for at least 48 hours after clinical improvement
• Then transition to oral therapy to complete 14 days total
• In cases with TOA: prefer clindamycin (not doxycycline) to complete oral therapy (better anaerobic coverage)

Follow-up

• Outpatients: re-evaluate at 72 hours - if not improving, hospitalise
• Sex partners must be empirically treated for gonorrhoea and chlamydia
• NAAT for persistent/recurrent infection after treatment if symptoms recur

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Fitz-Hugh-Curtis Syndrome (Perihepatitis)

• Occurs in 3-10% of PID cases
• Pleuritic RUQ pain and tenderness
• "Violin-string" adhesions between liver capsule and parietal peritoneum on laparoscopy
• Liver function tests and RUQ USS are nearly always normal
• Now most cases attributed to chlamydial (not gonococcal) salpingitis
• Diagnosed clinically: RUQ pain + MPC + adnexal tenderness in a young woman with normal gallbladder USS

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Surgery

• Rupture or threatened rupture of a tubo-ovarian abscess (TOA)
• Drainage of an abscess not responding to antibiotics
• Options: posterior colpotomy (for pelvic abscess drainage) and peritoneal lavage for generalised peritonitis

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Complications and Sequelae

Tubo-Ovarian Abscess (TOA)

• Most serious acute complication
• Develops in ~15% of hospitalised PID patients
• Requires parenteral antibiotics; surgical drainage if no response

Long-term Sequelae (from the Swedish salpingitis study):

• Ectopic pregnancy: 7-fold increased risk after PID (University of Washington data)
• Chronic pelvic pain: persistent in 20-30%
• Recurrent salpingitis
• Hysterectomy rate: 8-fold increased after PID

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Prevention

• Annual NAAT screening for C. trachomatis in all sexually active women ≤25 years (CDC / US Preventive Services Task Force recommendation)
• Screening reduces PID incidence by 56% (RCT evidence)
• Safe sex practices; prompt treatment of STIs
• Careful aseptic technique during intrauterine procedures

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Summary Table

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Anaemia in Pregnancy - 20 Marks

Definition

• <11 g/dL in the 1st and 3rd trimesters
• <10.5 g/dL in the 2nd trimester
• <10 g/dL is considered moderate; <7 g/dL is severe; <5 g/dL is very severe/critical

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Physiological Basis - Normal Haematologic Changes in Pregnancy

Key point: In physiological dilutional anaemia, MCV and MCHC remain normal. In true iron deficiency anaemia (IDA), both indices progressively decrease. This serial evaluation differentiates the two.

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Classification

By Aetiology (most practical for exam):

• Iron deficiency anaemia (IDA) - most common
• Megaloblastic anaemia (folate or B12 deficiency)
• Combined iron + folate deficiency

• Antepartum haemorrhage
• Hookworm infestation (chronic blood loss)

• Malaria (most common haemolytic cause in India)
• Sickle cell disease
• Thalassaemia
• Autoimmune haemolytic anaemia
• G6PD deficiency

• Aplastic anaemia
• Leukaemia

By Severity (WHO/India NFHS classification):

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Iron Requirements in Pregnancy

• The estimated daily requirement is 22-23 mg/day but median dietary intake in pregnancy is only ~15 mg/day
• Without supplementation, IDA will develop in most women
• Iron supplementation with 60 mg elemental iron/day reduces anaemia incidence by up to 73%

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Iron Deficiency Anaemia (IDA) - Stages

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Megaloblastic Anaemia in Pregnancy

• Second most common nutritional anaemia in pregnancy
• Usually due to folate deficiency; rarely due to B12 deficiency (fetus preferentially takes B12 from mother)
• Folate deficiency defined as serum level <2.5-3 ng/mL; RBC folate <140-150 ng/mL
• Risk increased by: multiple pregnancy, haemolytic anaemia, poor diet, anticonvulsants, OCP use, alcohol, sulfa drugs (all reduce conjugase activity in intestine)
• Peripheral smear: macro-ovalocytes, hypersegmented neutrophils (>5 lobes or any 6-lobed cell), megaloblastic change in marrow
• Treatment: Folic acid 1-5 mg/day orally; prevention: 0.4-0.5 mg folic acid daily from pre-conception (4 mg/day if prior NTD history)

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Risk Factors for Anaemia in Pregnancy

• Poor dietary iron and folate intake (low socioeconomic status)
• Repeated pregnancies at close intervals
• Menstrual losses (poor pre-pregnancy iron stores)
• Hookworm infestation (blood loss from gut)
• Malaria (haemolysis)
• Adolescent pregnancies
• Multiple gestation (increased demand)
• Prior history of anaemia

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Clinical Features

Symptoms:

• Fatigue, weakness, pallor, exertional dyspnoea, palpitations
• Headache, dizziness, tinnitus
• Pica (craving non-food items like clay, chalk - classic in IDA)
• Glossitis, angular stomatitis, koilonychia (IDA specific)
• Glossitis, peripheral neuropathy (B12 deficiency specific)

Signs:

• Pallor (conjunctival, mucosal, palmar)
• Tachycardia, wide pulse pressure
• Systolic flow murmur
• Oedema (in severe cases - "nutritional oedema")
• Splenomegaly (haemolytic causes)

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Investigations

• Hb at first antenatal visit, then at 28 and 36 weeks

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Effects on Mother and Fetus

Maternal effects:

• Increased risk of maternal mortality (RR 3.5 with Hb <5 g/dL)
• Postpartum haemorrhage (poor myometrial contraction + decreased blood reserve)
• Cardiac failure (high-output cardiac failure in severe anaemia)
• Increased risk of infection (iron deficiency impairs cellular immune function)
• Reduced work capacity and productivity
• Increased risk of preeclampsia

Fetal and neonatal effects:

• Preterm birth (>50% with Hb <5 g/dL in third trimester)
• Low birth weight / SGA neonates
• Stillbirth (with severe anaemia)
• Reduced fetal iron stores (cord blood ferritin correlates with maternal ferritin)
• Infant anaemia: 5.7-fold increased risk of anaemia at 1 year if mother was anaemic at delivery
• Neural tube defects (folate deficiency - hence periconceptional folic acid is mandatory)

Note: Paradoxically, very HIGH maternal Hb (>14.5 g/dL) is also associated with adverse outcomes (stillbirth, LBW, SGA) - thought to reflect inadequate plasma volume expansion and reduced intervillous blood flow.

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Treatment

Oral Iron Therapy

• First-line treatment for mild to moderate IDA
• Ferrous sulphate 200 mg (65 mg elemental iron) TDS = 195 mg elemental iron/day
• Or ferrous fumarate / ferrous gluconate equivalent
• Take on empty stomach with Vitamin C (enhances absorption); avoid with tea, milk, antacids
• Expected response: Hb rises ~1 g/dL per week
• Reticulocytosis peaks at 7-10 days after starting therapy
• Continue for 3 months after Hb normalises to replenish stores

• IFA tablet: 100 mg elemental iron + 0.5 mg folic acid daily
• If Hb 10-12 g/dL: supplementation
• If Hb <10 g/dL: refer to PHC

Parenteral (IV) Iron Therapy

• Indications: oral iron intolerance, malabsorption, severe anaemia near term (<34 weeks), non-compliance, failure of oral therapy
• Iron sucrose is most commonly used (safest profile in pregnancy)
• Dose formula: Weight (kg) × (Target Hb - Actual Hb) × 0.24 + 500 mg
• Target Hb = 11-12 g/dL; max daily infusion 200 mg (split over alternate days)
• IV iron superiority over oral: meta-analysis of 11 RCTs (>600 patients per group) showed significantly higher Hb and more patients achieving target Hb at 4 weeks
• Six parenteral forms approved in USA: iron sucrose, iron isomaltoside, ferric gluconate, low-MW iron dextran, ferumoxytol, ferric carboxymaltose
• Test dose required only for low-MW iron dextran (anaphylaxis risk)

Blood Transfusion

• Indications: Hb <7 g/dL with severe symptoms, Hb <5 g/dL regardless of symptoms, Hb <8 g/dL near term (>36 weeks), cardiac failure due to anaemia
• Packed RBCs preferred over whole blood
• 1 unit packed cells raises Hb by ~1 g/dL

Erythropoietin

• Used in cases where oral iron has failed and Hb <8.5 g/dL
• Normalises Hb in ~2 weeks in 73% of cases when added to oral iron
• Risk of thromboembolism to be considered

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Prevention

Antenatal:

• Routine IFA supplementation from first antenatal visit (100 mg elemental iron + 0.5 mg folic acid daily)
• Dietary counselling: increase iron-rich foods (green leafy vegetables, jaggery, meat), Vitamin C
• Deworming with albendazole 400 mg single dose (after first trimester)
• Malaria chemoprophylaxis in endemic areas

Preconceptional:

• Folic acid 0.4-0.5 mg/day from at least 1 month before conception (reduces NTD risk by ~70%)
• 4 mg/day if previous NTD-affected pregnancy
• Treat pre-existing anaemia before conception

Population level (India):

• National Nutritional Anaemia Prophylaxis Programme (NNAAP) - IFA tablets to pregnant women, lactating mothers, children
• Iron fortification of salt (National Institute of Nutrition, Hyderabad) - ferric orthophosphate or ferrous sulphate added to salt
• Screening at first ANC visit and at 28 and 36 weeks

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Summary Table

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