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Period-Delaying Medicines

1. Norethisterone (Most Common Option)

• Dose: 5 mg (1 tablet) three times a day
• Start taking it 3 days before your expected period
• Continue until you want your period to begin
• Can be used for up to 17-27 days (per most prescribing guidance)
• Your period will usually arrive 2-3 days after stopping

• It is not a contraceptive - it will not prevent pregnancy
• Requires a prescription in most countries
• Not suitable if you have a history of blood clots, liver disease, or are pregnant

• Nausea
• Breast tenderness
• Bloating
• Headaches
• Mood changes
• Spotting/breakthrough bleeding

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2. Combined Oral Contraceptive Pill (COC)

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3. Medroxyprogesterone Acetate (Provera)

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Comparison at a Glance

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Who Should Not Use These Medicines

• Pregnant or possibly pregnant women
• Those with a history of blood clots (DVT/PE)
• History of breast or hormone-sensitive cancer
• Severe liver disease
• Unexplained vaginal bleeding
• Those with migraine with aura (COC is especially contraindicated)

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Disclaimer: These medicines require a doctor's prescription. Always consult a healthcare professional before starting, as suitability depends on your medical history, current medications, and individual circumstances. Do not self-medicate.

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Fibroadenosis (Benign Breast Disease / ANDI)

Nomenclature

ANDI - Aberrations of Normal Development and Involution

• Bailey and Love's Short Practice of Surgery, 28th Ed., p. 940
• S Das Manual on Clinical Surgery, 13th Ed., p. 432

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Definition

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Epidemiology

• Affects women between 20-50 years (reproductive age)
• Incidence falls sharply after menopause (unlike breast carcinoma)
• More common in:
  • Nulliparous women (spinsters, childless married women)
  • Women who have not breastfed their children
• Higher incidence in western countries (England, Wales)

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Aetiology

• Cyclical hormonal imbalances
• Oral contraceptives and HRT
• Diet and smoking
• High caffeine intake (proposed, not strongly proven)

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Pathology

Microscopic Features:

• Adenosis - increase in number of acini per lobule
• Cyst formation - micro- and macrocysts (kinking/narrowing of ductules causes secretion accumulation)
• Epithelial hyperplasia - >2 cell layers lining ducts/acini
  • With atypia: Atypical Ductal Hyperplasia (ADH) or Atypical Lobular Hyperplasia (ALH)
• Papillomatosis
• Fibrosis
• Lymphocytic infiltration

Key: If ADH involves >2 ducts or the lesion is >2 mm, the term DCIS is used. - Bailey & Love, p. 940

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Clinical Features

Symptoms

1. Breast pain (Mastalgia) - the dominant symptom
   • Cyclical (premenstrual): starts around day 14, worsens until day 27-28, relieved by onset of menses
   • Both breasts usually involved; may radiate to the upper arm
   • Non-cyclical: persistent, well-localised, not related to the cycle
2. Nodularity / Lump - often multiple lumps, bilateral, upper and outer quadrant predominance
   • Lumps become larger and more tender premenstrually
   • Size fluctuates with the cycle - this almost excludes carcinoma
3. Nipple discharge - greenish or serous

Signs

• Multiple, firm, rubbery nodules - best felt by fingers and thumb (not palmar surfaces)
• Usually bilateral, upper outer quadrant
• Nodules are not fixed to skin or pectoralis fascia
• Cysts - smooth, round, variable consistency; very tense cysts may feel hard and non-fluctuant
• Axillary lymph nodes: occasionally slightly enlarged and tender
• "Blue-domed cyst of Bloodgood" - appearance of a solitary breast cyst

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Investigations

Triple Assessment (the cornerstone):

1. Clinical examination
2. Imaging
   • Mammography (women >35 years)
   • Ultrasound (younger women with dense breasts)
3. Fine Needle Aspiration Cytology (FNAC)
   • Aspirate from cyst: if non-blood-stained, no residual lump after aspiration, cyst does not refill, and cytology is benign → benign diagnosis confirmed

Criteria for a benign cyst on aspiration:

1. Aspirate is not blood-stained
2. No residual lump after aspiration
3. Cyst does not refill
4. Cytology shows no malignant cells

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Cancer Risk

• Simple fibroadenosis: no significantly increased risk
• Epithelial hyperplasia without atypia: RR ~1.5-2x
• Atypical ductal/lobular hyperplasia: RR ~4-5x
• Papillomatosis (5+ papillomas): RR ~3x
• Positive family history of breast cancer further increases lifetime risk

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Treatment

1. Reassurance and Explanation

• Most important step - the patient must be reassured that the condition is benign
• Explain the cyclical nature of symptoms

2. Mastalgia Management

• Well-fitted, supportive bra (worn 24 hours/day if needed)
• NSAIDs / analgesics
• Evening primrose oil (gamma-linolenic acid) - first-line non-hormonal option

• Danazol (anti-gonadotropin) - effective but androgenic side effects (acne, hirsutism, voice changes)
• Tamoxifen (anti-oestrogen) - effective; used in low doses (10-20 mg/day)
• Ormeloxifene (selective oestrogen receptor modulator)
• Bromocriptine (dopamine agonist / prolactin inhibitor) - less used now due to side effects
• GnRH analogues - for severe refractory cases

3. Cyst Management

• Aspiration - both diagnostic and therapeutic
• If cyst recurs after 2-3 aspirations or cytology is atypical → surgical excision

4. Surgical Treatment

• Dominant, discrete lump that is uncertain after triple assessment
• Atypia on cytology/histology
• Patient preference

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Differential Diagnosis

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Key Points to Remember

• Fibroadenosis = ANDI = benign mammary dysplasia - all refer to the same spectrum
• It is the most common cause of a breast lump in reproductive-aged women
• The cyclical fluctuation in lump size is almost pathognomonic and effectively excludes carcinoma
• Triple assessment (clinic + imaging + FNAC) is mandatory before labelling any breast lump as benign
• Epithelial hyperplasia with atypia carries a significantly elevated cancer risk and warrants close follow-up

Sources: Bailey and Love's Short Practice of Surgery, 28th Ed., pp. 939-944; S Das Manual on Clinical Surgery, 13th Ed., pp. 432-434

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Viral Hepatitis A - Treatment Protocol

First: Interpreting This Patient's Values

• Prothrombin time / INR (most important prognostic marker)
• Hepatic encephalopathy (confusion, flapping tremor)
• Serum albumin
• Blood glucose (hypoglycemia = poor sign)
• Serum creatinine

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Core Principle

There is NO specific antiviral treatment for Hepatitis A. HAV infection is self-limited. Management is entirely supportive. - Goldman-Cecil Medicine, p. 1568

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Treatment Protocol

Step 1 - Confirm Diagnosis

• Anti-HAV IgM (ELISA) - peaks in the second month; diagnostic for acute infection
• IgM anti-HAV disappears after 4-12 months; IgG persists for life
• HAV RNA PCR in stool (not routinely necessary)
• Exclude Hep B (HBsAg, anti-HBc IgM) and Hep C (anti-HCV)

Step 2 - Assess Severity and Decide Admission

• Bilirubin >10 mg/dL ✓ (patient has 13.2)
• Inability to maintain oral intake (nausea, vomiting)
• Signs of dehydration
• PT/INR prolonged (>1.5)
• Any encephalopathy
• Age >50 years or underlying chronic liver disease
• Immunocompromised state

"In severe cases, patients may need to be hospitalized. If liver function is deteriorating, patients may need to be assessed for liver transplantation." - Goldman-Cecil Medicine, p. 1568

"About 3-8% of FHF cases are caused by HAV; however, only 1-2% of HAV infections in adults lead to FHF." - Medscape/Emedicine

Step 3 - Supportive In-Hospital Care

A. Rest and Activity

• Bed rest during the acute symptomatic phase
• Return to work/school only after fever and jaundice have cleared
• Restrict physical exertion until symptoms resolve

B. Diet and Nutrition

• High-calorie, high-carbohydrate, low-fat diet
• Small, frequent meals (better tolerated when nauseated)
• Encourage oral fluids - aim for adequate hydration
• If oral intake is severely impaired: IV fluids (Normal saline or Dextrose-saline)
• Avoid fatty foods (worsens nausea)

C. Medications - STRICT RESTRICTIONS

D. Symptomatic Treatment

E. Monitoring (Daily in Severe Cases)

• Liver function tests (bilirubin, ALT, AST) - every 2-3 days
• Prothrombin time / INR - daily (key prognostic marker)
• Blood glucose - daily
• Serum electrolytes - daily
• Serum creatinine and urea
• Full blood count
• Mental status assessment (for encephalopathy)

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Red Flags - Fulminant Hepatic Failure (FHF)

• Hepatic encephalopathy (confusion, drowsiness, flapping tremor/asterixis)
• PT >3 seconds above control / INR >1.5 and rising
• Serum bilirubin rapidly rising (>1 mg/dL/day)
• Hypoglycemia (falling blood sugar)
• Falling transaminases WITH worsening bilirubin and INR = "enzyme burn-out" - a sinister sign
• Oliguria / renal failure
• Metabolic acidosis

"Acute liver failure (ALF) is a clinical syndrome of liver injury (elevated transaminases), hepatic encephalopathy, and coagulopathy (elevated PT/INR) in patients without preexisting liver disease." - Sabiston Textbook of Surgery

1. Transfer immediately to a liver transplant centre
2. ICU-level monitoring
3. Lactulose 20-30 mL TDS (for encephalopathy - to reduce ammonia)
4. Rifaximin 550 mg BD (adjunct for encephalopathy)
5. Vitamin K IV (for coagulopathy)
6. Fresh Frozen Plasma (FFP) if active bleeding or invasive procedure planned
7. Correct hypoglycemia aggressively with IV dextrose
8. Avoid sedatives/opioids (worsen encephalopathy)
9. Assess for liver transplantation using King's College Criteria

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King's College Criteria (Transplant Referral - Non-Acetaminophen Cause)

• PT >100 seconds (INR >6.5), OR
• Any 3 of the following:
  • Age <10 or >40 years
  • Aetiology: non-A, non-B hepatitis / drug reaction / Wilson's disease
  • Jaundice >7 days before encephalopathy
  • PT >50 seconds
  • Serum bilirubin >300 µmol/L (>17.5 mg/dL)

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Isolation and Infection Control

• HAV is faecal-oral transmission - highly contagious during the prodrome and early icteric phase
• Enteric (contact) precautions during hospitalization
• Hand hygiene is essential
• Stool and blood precautions
• Patient is most infectious 2 weeks before jaundice appears and for ~1 week after

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Post-Exposure Prophylaxis for Contacts

• HAV vaccine (within 2 weeks of exposure) - ~98% effective
• Immunoglobulin (Ig) 0.1 mL/kg IM (within 2 weeks) - if vaccine contraindicated or patient is immunocompromised/elderly
• Both can be given together without reducing vaccine efficacy

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Prognosis for This Patient

• Acute HAV is entirely self-limited - no progression to chronic hepatitis, cirrhosis, or cancer
• Typically resolves in 3-4 weeks
• Transaminases will fall first, bilirubin normalizes last
• Fulminant HAF occurs in <0.1% of cases overall; risk increases with age >50 and pre-existing liver disease
• Mortality from uncomplicated hepatitis A is very low
• Cholestatic HAV (as suggested by bilirubin 13.2) has a good prognosis with full recovery within weeks

"Acute hepatitis A infection generally resolves without complications in 3 to 4 weeks and never evolves to chronic infection." - Goldman-Cecil Medicine, p. 1568

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Summary Card for This Patient

Sources: Goldman-Cecil Medicine International Edition, p. 1568; Sabiston Textbook of Surgery; Merck Manual Professional Ed. (updated Apr 2025); Medscape - Hepatitis A Treatment & Management

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Fulminant Hepatic Failure (FHF) - Diagnosis

Terminology

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Definition

ALF = Acute liver injury (elevated transaminases) + Hepatic Encephalopathy + Coagulopathy (INR ≥ 1.5) in a patient WITHOUT pre-existing liver disease.

• Sabiston Textbook of Surgery
• Yamada's Textbook of Gastroenterology, 7th Ed.

"The combination of coagulopathy and encephalopathy is unique provided that underlying cirrhosis has been excluded." - Yamada's Textbook of Gastroenterology

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Classification by Time (Onset of Jaundice to Encephalopathy)

"Shorter duration to encephalopathy (hyperacute) more commonly leads to cerebral edema; longer duration leads to portal hypertension." - Sabiston Textbook of Surgery

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Causes of ALF

• Sleisenger & Fordtran's GI and Liver Disease

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Clinical Features

1. Encephalopathy (GRADING - West Haven Criteria)

"Mental alterations may be subtle initially - agitation and confusion - then rapid progression to deeper coma. In a young person, agitation may be mistaken for CNS stimulant ingestion; sedation is inappropriate as the liver cannot metabolize CNS depressants." - Yamada's Textbook of Gastroenterology

2. Jaundice

• Usually present (deep jaundice)
• May be absent or mild in hyperacute cases (especially acetaminophen)
• Cholestatic pattern in subacute disease

3. Coagulopathy

• Prolonged PT/INR (most reliable prognostic marker)
• Bleeding tendency (GI bleed, intracranial bleed)
• DIC may develop in late disease

4. Cerebral Oedema

• Almost unique to ALF (rarely seen in cirrhosis)
• Causes >20% of deaths in ALF
• Manifests as: rising BP, bradycardia, abnormal pupil reflexes, decerebrate posturing
• Leads to herniation and brain death if untreated

5. Haemodynamic Instability

• Hypotension + vasodilation + low systemic vascular resistance (resembles gram-negative sepsis)
• Compensatory tachycardia

6. Other Organ Failures

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Diagnostic Investigations

Mandatory at Presentation

Aetiology-Specific Tests

Imaging

"Liver enlargement in ALF is unusual except in Budd-Chiari; should trigger consideration of malignant infiltration or alcohol-associated hepatitis." - Sleisenger & Fordtran's

"CT/MRI are relatively insensitive for detection of cerebral oedema but can exclude intracranial haemorrhage as a cause of deterioration." - Yamada's Textbook of Gastroenterology

Liver Biopsy

• Not routinely performed in ALF
• Findings of confluent necrosis and parenchymal collapse are non-specific
• Indicated when: suspicion of malignant infiltration or alcohol-associated hepatitis - especially if transplant listing is under consideration
• Can support diagnosis of: autoimmune hepatitis, Wilson disease, AFLP, Budd-Chiari

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Prognostic Scoring

King's College Criteria (1989)

For NON-Paracetamol Causes:

• INR > 6.5 (PT >100 sec) at any time, OR
• Any 3 of the following:
  • Age <10 or >40 years
  • Aetiology: non-A/non-B hepatitis, drug-induced liver injury, Wilson disease
  • Duration of jaundice >7 days before encephalopathy
  • PT > 50 sec (INR >3.5)
  • Serum bilirubin >300 µmol/L (>17.5 mg/dL)

For Paracetamol (Acetaminophen) Causes:

• Arterial pH < 7.30 after resuscitation, OR
• All 3 of:
  • PT > 100 sec (INR > 6.5)
  • Serum creatinine > 3.5 mg/dL (>292 µmol/L)
  • Grade III or IV hepatic encephalopathy

"Specificity of King's College Criteria: 82% for non-acetaminophen, 95% for acetaminophen ALF. Sensitivity ~58% (relatively low - do not use to rule out)." - Sleisenger & Fordtran's

Clichy Criteria (France)

• Factor V < 20% in patients < 30 years, OR
• Factor V < 30% in patients ≥ 30 years
• With grade 2 or greater encephalopathy
• Limitations: not effective for acetaminophen ALF

MELD Score

• MELD = 3.78×ln[bilirubin mg/dL] + 11.2×ln[INR] + 9.57×ln[creatinine mg/dL] + 6.43
• Has been validated for ALF but not superior to King's College Criteria

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Prognosis

"Trends over time in mentation and PT/INR are the best indicators of overall prognosis at the bedside." - Yamada's Textbook of Gastroenterology

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Diagnostic Algorithm Summary

Acute illness → Jaundice + Rising PT/INR
        ↓
Assess for Encephalopathy (mandatory for ALF diagnosis)
        ↓
If encephalopathy present:
  → Confirm NO pre-existing liver disease/cirrhosis
  → Classify timing (hyperacute / acute / subacute)
  → Run full aetiology workup (IgM serology, paracetamol level, autoimmune, Wilson)
  → Assess organ failure (renal, metabolic, cerebral)
  → Apply King's College Criteria
  → If criteria met → IMMEDIATE transfer to liver transplant centre
        ↓
Monitor: PT/INR, glucose, ammonia, creatinine, GCS/encephalopathy grade DAILY

Sources: Sleisenger & Fordtran's GI and Liver Disease; Yamada's Textbook of Gastroenterology 7th Ed.; Sabiston Textbook of Surgery; Mulholland & Greenfield's Surgery 7th Ed.

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Herpetic Ulcer of the Lower Lip (Herpes Labialis) - Treatment Protocol

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Background

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Clinical Stages and Appearance

Key fact: Treatment is ONLY effective if started in the prodrome or erythema stage - once frank ulceration occurs, benefit is minimal.

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Diagnosis

• Clustered vesicles/ulcers at the vermilion border of the lip
• History of recurrence in the same location
• Prodrome of tingling/burning

• Direct Fluorescent Antibody (DFA) test - fastest, results in hours (preferred)
• Viral culture from vesicle base - gold standard but takes 2-5 days
• Tzanck smear - shows multinucleated giant cells (not HSV-specific, but suggestive)
• PCR - most sensitive, used in atypical or severe cases
• Serology (HSV IgM/IgG) - not useful for acute disease; only establishes serostatus

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Treatment Protocol

A. Recurrent Herpes Labialis (Most Common Presentation)

1. Topical Therapy (First-Line for Mild Cases)

"Penciclovir 1% cream every 2 hours while awake for 4 days - when initiated within 1 hour of first symptoms, speeds healing (4.8 vs 5.5 days) and decreases pain duration." - Fitzpatrick's Dermatology

2. Oral Antiviral Therapy (For Moderate-Severe or Faster Resolution)

"For herpes labialis, 1 day of therapy with oral valacyclovir improves time to healing and reduces pain, whereas acyclovir ointment has no consistent clinical benefit." - Goldman-Cecil Medicine

"A single dose of famciclovir (1500 mg) reduced time to healing of herpes labialis lesions by approximately 2 days compared with placebo." - Fitzpatrick's Dermatology

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B. Primary (First Episode) Herpetic Gingivostomatitis

"The pediatric dose is 15 mg/kg of acyclovir suspension orally 5 times a day for 7 days. When started within 3 days of onset, this regimen decreases the duration of oral and extraoral lesions, fever, and eating and drinking difficulties." - Fitzpatrick's Dermatology

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C. Suppressive Therapy (For Frequent Recurrences ≥6/year)

• Review annually - take a "holiday" each year to reassess whether suppression is still needed
• Sunscreen to lips helps prevent UV-triggered recurrences (benefit shown in some trials)

"The use of suppressive acyclovir for herpes labialis is controversial. Suppressive valacyclovir reduces recurrence frequency and severity in those with frequent episodes." - Fitzpatrick's Dermatology

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D. Immunocompromised Patients (HIV, Transplant)

• Lesions are larger, more numerous, more persistent, more frequent
• First-line: oral famciclovir, valacyclovir, or acyclovir for 7 days
• Severe lesions: IV acyclovir (5-10 mg/kg every 8 hours)
• Daily suppressive therapy should be considered for frequent/severe recurrences
• If lesions persist despite adequate treatment: culture for acyclovir resistance
• Acyclovir-resistant HSV: IV foscarnet is the treatment of choice
• Cummings Otolaryngology

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Symptomatic / Supportive Care

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Infection Control / Patient Advice

• Avoid kissing or direct contact during active lesions
• Avoid touching lesions and then touching eyes (risk of herpetic keratitis - sight-threatening)
• Wash hands frequently
• Do not share lip balm, utensils, towels, or cups during active outbreak
• Lesions are most contagious from prodrome through ulceration (before crust forms)
• Sunscreen/lip balm with SPF - apply daily to prevent sun-triggered recurrences

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When to Refer / Escalate

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Summary: Quick Treatment Decision Guide

Lower lip herpetic ulcer
       ↓
Prodrome / erythema only (caught early)?
  YES → Penciclovir 1% cream q2h × 4 days
        OR Valacyclovir 2g BD × 1 day
        OR Famciclovir 1500mg single dose
        + Paracetamol for pain
        + Lip balm SPF
  NO (already ulcerated/crusted) →
        Supportive care only (antivirals have minimal benefit at this stage)
        Topical anaesthetic for pain relief
        Keep clean, prevent secondary infection
       ↓
Frequent recurrences (≥6/year)?
  → Add suppressive Acyclovir 400mg BD or Valacyclovir 500mg OD
       ↓
Immunocompromised / severe disease?
  → Oral antivirals × 7-10 days or IV Acyclovir
  → Check for acyclovir resistance if not responding
  → Foscarnet IV if resistant

Sources: Fitzpatrick's Dermatology, Vol 1; Goldman-Cecil Medicine International Edition; Washington Manual of Medical Therapeutics; Textbook of Family Medicine 9th Ed.; Cummings Otolaryngology Head & Neck Surgery