(a) A 25 year old female has presented to the medicine OPD with complaints of excessive tiredness, cold intolerance and menstrual…

(a)(i) Thyroid disorder

Tiredness, cold intolerance and menstrual irregularity (menorrhagia or oligomenorrhoea) in a young woman indicate primary hypothyroidism, most often due to autoimmune (Hashimoto) thyroiditis.

(a)(ii) Cardiovascular features: hypothyroidism versus hyperthyroidism

• Heart rate and rhythm: sinus bradycardia, versus sinus tachycardia and atrial fibrillation (especially in the elderly).
• Blood pressure: diastolic hypertension with narrow pulse pressure (raised peripheral resistance), versus systolic hypertension with wide pulse pressure and collapsing pulse.
• Cardiac output and contractility: reduced stroke volume and output, versus hyperdynamic circulation with raised output.
• Heart sounds and murmurs: soft heart sounds, versus loud S1, ejection flow murmur and Means–Lerman scratch.
• Pericardium and failure: pericardial effusion and, rarely, heart failure, versus high-output heart failure and thyrotoxic cardiomyopathy.
• Lipids and coronary disease: hypercholesterolaemia and accelerated atherosclerosis, versus low cholesterol and angina from increased demand.
• ECG: low voltage, prolonged QT and flat T waves, versus tachycardia, atrial fibrillation and short PR.

(a)(iii) Drug treatment and monitoring

Hypothyroidism: levothyroxine (T4) once daily on an empty stomach 30–60 minutes before breakfast, full dose about 1.6 μg/kg/day in young healthy adults, starting low (12.5–25 μg) in the elderly or those with heart disease, adjusted by 12.5–25 μg every 6–8 weeks. Monitor serum TSH 6–8 weeks after each change, then yearly (target in the reference range, roughly 0.5–2.5 mIU/L). In central hypothyroidism, follow free T4 instead. Hyperthyroidism:

• Antithyroid drugs: carbimazole or methimazole (10–40 mg/day, titration or block-and-replace) for 12–18 months. Propylthiouracil in the first trimester of pregnancy and in thyroid storm.
• β-blockers (propranolol 20–40 mg three to four times daily) for symptoms.
• Definitive: radioactive iodine (¹³¹I) or thyroidectomy for relapse, large goitre or toxic nodular disease. Monitoring: free T4 and free T3 every 4–6 weeks during titration, since TSH may stay suppressed for months, then TSH. Baseline and symptom-driven CBC (agranulocytosis) and liver function tests, and TSH receptor antibodies to predict relapse before stopping.

(b)(i) IMNCI assessment and classification of a young infant (up to 2 months)

Ask: convulsions, ability to feed. Look and listen: count breaths in one minute (repeat if 60 or more), severe chest indrawing, nasal flaring, grunting, bulging fontanelle, umbilicus (red or draining pus, redness extending to skin), skin pustules (number and severity), temperature (axillary 37.5 °C or more, or below 35.5 °C), and movement (only when stimulated or none).

• Possible serious bacterial infection (PSBI): any one of not able to feed, convulsions, fast breathing (60 or more per minute), severe chest indrawing, nasal flaring or grunting, bulging fontanelle, fever or hypothermia, umbilical redness extending to skin, 10 or more or severe pustules, lethargy or reduced movement.
• Local bacterial infection: umbilicus red or draining pus, or skin pustules few in number, with none of the above signs.
• Infection unlikely: none of these. This 6-week-old is sick-looking, so careful assessment usually places the baby in PSBI.

(b)(ii) Treatment as per IMNCI

PSBI:

• First dose of intramuscular antibiotics: ampicillin (50 mg/kg) or benzylpenicillin with gentamicin (5 mg/kg for term babies).
• Treat or prevent hypoglycaemia (breast milk, expressed milk or sugar water by spoon or nasogastric tube).
• Keep warm (skin-to-skin contact) and refer urgently, with advice to continue breastfeeding.
• If referral is not possible: gentamicin intramuscularly once daily for 7 days with oral amoxicillin twice daily for 7 days, with follow-up. Infants aged 7–59 days with fast breathing as the only sign may be treated with oral amoxicillin for 7 days without referral. Local bacterial infection:
• Oral amoxicillin twice daily for 5 days.
• Clean the umbilicus or pustules and apply gentian violet (0.5%) twice daily, teach the mother to do so at home.
• Continue exclusive breastfeeding, keep the infant warm, and follow up in 2 days, returning at once if danger signs appear.

(c)(i) Differential diagnosis

• Stevens–Johnson syndrome / toxic epidermal necrolysis (most likely): lamotrigine, 1–4 weeks after starting, tender purpuric macules and bullae with mucosal involvement of lips, mouth and eyes. Positive Nikolsky sign. Classified by detached area.
• DRESS (rash, fever, eosinophilia, organ involvement, longer latency).
• Erythema multiforme major (target lesions on extremities, usually after HSV or Mycoplasma).
• Staphylococcal scalded skin syndrome (mostly children, no mucosal involvement).
• Autoimmune bullous disease (pemphigus vulgaris, paraneoplastic pemphigus) and generalised bullous fixed drug eruption.

(c)(ii) Management

• Stop lamotrigine immediately and permanently, record the reaction, avoid re-challenge. Use a structurally unrelated antiseizure drug (for example levetiracetam or valproate), avoiding aromatic anticonvulsants (carbamazepine, phenytoin, phenobarbital) which can cross-react.
• Assess severity with SCORTEN and admit to an ICU or burn unit: barrier nursing, warm environment (30–32 °C), IV fluids guided by urine output, nutrition, analgesia, and non-adherent dressings without aggressive debridement.
• Eye care with ophthalmology (lubricants, topical antibiotics, preventing symblepharon), oral care (antiseptic mouthwash, analgesic gels), and genital and urinary care.
• Watch for sepsis, treating infections according to cultures without routine prophylaxis.
• Immunomodulation in selected cases: ciclosporin (3–5 mg/kg/day), IVIG, or etanercept, as per local protocol.