Immune Checkpoint Inhibitor Toxicity — DCE Clinical Case

The patient

Mr K is a 64-year-old retired engineer who was diagnosed with metastatic melanoma (BRAF wild-type, PD-L1 positive) eight months ago. He commenced combination ipilimumab and nivolumab four months ago and has tolerated the first three cycles well, with a partial response on the most recent CT. Three weeks ago he developed loose stools, which have progressed to eight bloody bowel motions per day with mucus, abdominal cramps and urgency. Over the same period he has noticed a diffuse itchy rash over his trunk, profound fatigue, and dizziness on standing. He has lost 4 kg. He is otherwise well, takes no regular medications, and has no prior autoimmune disease. ^[1]

Examination findings

• General: alert but fatigued, mildly jaundiced. Diffuse maculopapular rash over the trunk, confluent, involving approximately 25 per cent of body surface area. No mucosal involvement.
• Vital signs: heart rate 108, blood pressure 104/62 lying and 88/54 standing, respiratory rate 20, oxygen saturation 96 per cent on room air, temperature 37.4.
• Abdomen: diffuse tenderness, no peritonism, bowel sounds hyperactive, no organomegaly.
• Respiratory: fine bibasal crackles.
• Cardiovascular: no murmur, no rub, no raised JVP.
• Neurological: no ptosis, no fatigability, no focal deficit, GCS 15.
• Endocrine: no thyroid bruit, no hyperpigmentation; confrontation visual fields show a mild bitemporal restriction. ^[1]

Investigations

• Sodium 126, potassium 5.1, urea 9.2, creatinine 140 (baseline 88).
• ALT 260, AST 210, ALP 180, bilirubin 58, INR 1.3, albumin 28.
• Haemoglobin 112, white cells 14.6, eosinophils 0.4, platelets 230.
• TSH 16.4 mU/L (high), free T4 6 pmol/L (low), random cortisol 70 nmol/L (low), ACTH 5 ng/L (low), FSH low, LH low, testosterone low, prolactin mildly raised.
• Troponin normal. ECG normal sinus rhythm.
• Stool culture, C. difficile toxin, ova cysts and parasites sent, results pending.
• Hepatitis A, B, C and E serology, CMV and EBV PCR, autoimmune markers — pending.
• Abdominal ultrasound with Doppler — pending. ^[1]