Multimorbid woman in her sixties with abdominal pain and dark stools

A woman in her sixties was admitted to hospital as an emergency with abdominal pain, low haemoglobin, dark stools and suspected gastrointestinal bleeding. She had been living in Norway for decades but was originally from Southeast Asia, and had visited her country of origin regularly. She was known to have α-thalassemia, gout, diet-controlled type 2 diabetes and hypertension. She had been hospitalised the preceding year with cerebral haemorrhage. A brain MRI three months later found regression of the haemorrhagic lesions and a small sequela of cerebral infarction, after which treatment with clopidogrel and atorvastatin was initiated. Due to repeated flares of gout and a history of presumed allergic reaction to allopurinol, the patient's general practitioner had intermittently prescribed 5 mg prednisolone and probenecid tablets. The patient had recently been started on treatment with daily 20 mg prednisolone tablets due to an episode of gout.

In the emergency department, the woman was hypertensive with blood pressure of 187/81 mmHg. Other vital signs were normal. A faecal occult blood test was positive, and the patient's haemoglobin was 9.8 g/dL (reference range 11.7–15.3). Since there was no suspicion of an acute life-threatening haemorrhage, she was started on a proton-pump inhibitor and received an iron infusion. She was discharged and referred for rapid outpatient gastroscopy due to a presumed gastric ulcer caused by the combination of prednisolone and clopidogrel. The clopidogrel was paused for five days, and the prednisolone was discontinued without tapering.

The woman was re-admitted two days later with non-specific twitching in her extremities, but she was not otherwise uncomfortable or feverish. She reported that her general condition had been poor in the previous few days, with pollakiuria and a slight cough over the preceding 2–3 weeks, but no other specific symptoms. Her haemoglobin was 9.1 g/dL (11.7–15.3), CRP 94 mg/L (< 5), leukocytes 9.87 × 10⁹/L (3.5–10.0 × 10⁹) and eosinophils 0.24 × 10⁹/L (< 0.4 × 10⁹). Creatinine was 109 µmol/L (45–90), sodium 132 mmol/L (137–145) and potassium 4.7 mmol/L (3.5–5.0). She had high plasma glucose of 24 mmol/L (fasting 4.0–6.0) and HbA1c of 82 mmol/mol (20–42). A chest X-ray showed a small retrocardiac opacity, unchanged from previous imaging. A urine dipstick was positive for nitrite, protein 1+, ketones 2+, glucose 4+, but she did not have pyuria or dysuria.

Unfortunately, urine was not sent for culturing before the initiation of ampicillin and gentamicin adjusted for renal function to treat a suspected respiratory or urinary tract infection. Half a day later, blood cultures were found to be positive for Klebsiella pneumoniae.

A short while later, the woman started to vomit and passed a large amount of melena. She became hypotensive (blood pressure 94/38 mmHg), tachycardic (heart rate approximately 120 bpm), somnolent and exhibited an inadequate response when addressed. She did not have hypoxemic respiratory failure or dyspnoea, but arterial blood gas analysis revealed metabolic acidosis with respiratory compensation and pH 7.44 (7.36–7.44), pCO₂ 2.1 kPa (4.5–6.1), pO₂ 13.1 kPa (9.6–12.4), HCO₃ 11 mmol/L (20–26) and base excess −13.1 mmol/L (± 3.0). In addition, capillary blood beta-hydroxybutyrate (ketones in blood) was found to be elevated at 5.3 mmol/L (< 0.6). Her blood pressure increased with intensive fluid therapy, and the antibiotic treatment was changed to cefotaxime. A brain MRI demonstrated small subacute cerebral infarctions, but the patient had no neurological deficits. Lumbar puncture was not performed due to recent treatment with clopidogrel, and she had a fluctuating level of consciousness associated with severe infection/sepsis. It emerged that, prior to admission, the patient had been on 5 mg prednisolone for longer than previously thought. Due to circulatory failure and suspected iatrogenic adrenal insufficiency as a result of prolonged steroid use and sudden discontinuation of prednisolone, the patient was administered 50 mg intravenous hydrocortisone four times a day.

Gastroscopy on day two revealed a 2 × 4 cm antral ulcer with no stigmata of bleeding or signs of perforation. It was assumed that a bleeding ulcer was the cause of the decrease in haemoglobin, and no biopsy was taken due to the risk of haemorrhage.

There was a gradual improvement in the patient's condition. On day 13, she was discharged to a nursing home with 500 mg ciprofloxacin tablets twice daily for three days and follow-up gastroscopy arranged for two weeks later. Prednisolone was tapered and discontinued before discharge. The woman was in a fatigued and weakened condition, but she appeared stable and without signs of infection.

She was re-admitted three days later due to elevated CRP, low blood pressure, cardiac arrhythmia, abdominal pain, frequent loose stools and presumed therapeutic failure. She had pitting oedema, was subfebrile (body temperature 37.7°C), tachycardic (heart rate 103 bpm) and hypotensive (blood pressure 77/54 mmHg), but responded well to fluid resuscitation. She had acute renal failure with creatinine of 211 µmol/L (45–90), as well as hyponatraemia 127 mmol/L (137–145) and potassium 4.4 mmol/L (3.5–5.0). The patient's albumin was 18 g/L (32–43), and she was presumed to have intravascular volume depletion. Leukocytes, eosinophils and CRP were elevated at 16.1 × 10⁹/ L, 1.23 × 10⁹, and 176 mg/L, respectively. Intravenous piperacillin/tazobactam was initiated in the emergency department, but this was rapidly discontinued due to a suspected Clostridioides difficile infection.

Faecal samples were negative for C. difficile toxins A and B. The woman developed a fever, and urine culture yielded Enterococcus faecium. It was decided to cautiously take this finding into account and start intravenous treatment with linezolid. The patient underwent colonoscopy due to persistent diarrhoea and elevated faecal calprotectin of 523 mg/kg (< 50). There were no macroscopic signs of colitis. Routine mucosal biopsies were taken, including a mucosal sample with the appearance of a sessile polyp.

The patient was stable, but nauseous and anorectic, and experiencing increasing gout pain. After initiation of 20 mg prednisolone tablets once daily and 0.5 mg colchicine tablets three times daily, her CRP decreased to 11, and her clinical condition improved with almost normal bowel movements and no abdominal pain. Eosinophils decreased from 3.49 × 10⁹/L to 0.78 × 10⁹/L. The eosinophilia was interpreted as either non-specific or drug-induced. After eight days in hospital, the woman was discharged to a nursing home with 600 mg linezolid tablets twice daily for a total of 7 days, a short course of prednisolone, nystatin suspension, insulin and nutrition drinks. The findings of the mucosal biopsy were received after discharge and demonstrated both acute and chronic inflammation, but no eosinophilia. No polyp tissue was found.

The day following discharge, the woman was referred to the emergency department for the fourth time in a month with increasing dyspnoea, heart rate > 130 bpm and recurrence of abdominal pain. On admission, she was somnolent, tachycardic and slightly hypothermic (35.7 °C). She had normal blood pressure and oxygen saturation. Recurrence of severe ketoacidosis was detected with beta-hydroxybutyrate of 6.0 mmol/L, HCO₃ 2.0 mmol/L and pH 6.98, despite respiratory compensation and PaCO₂ of 1.6 kPa. pO₂ was 15.0 kPa, and lactate was slightly elevated at 2.3 mmol/ L (0.5–1.6). The patient was transferred to the intensive care unit, where she received standard treatment for ketoacidosis. There was no change in her haemoglobin levels but a slight deterioration in her renal function with creatinine at 123 µmol/L. CRP was 9.5 mg/L, leukocytes 22.7 × 10⁹/L and eosinophils 0.04 × 10⁹/L. Blood cultures were negative, but growth of E. coli was found in a urine sample. Intravenous cefotaxime was initiated for a presumed urinary tract infection. Intravenous fluids and enteral nutrition were administered due to extreme nausea. Gastroscopy was repeated and revealed a fibrin-covered ulcer, and biopsies were taken from the ulcer margin.

The woman's condition gradually improved, and after three days she was transferred to a ward. However, she developed a gout flare in her right index finger and recurrence of eosinophilia at 3.06 × 10⁹/L (< 0.4). A sample was sent for Strongyloides serology and a stool sample was sent for microscopy. The findings of the gastric biopsy were returned the same day and demonstrated histopathological changes consistent with Strongyloides larvae (Figure 1a). An abundance of Strongyloides larvae was also detected in stools, and Strongyloides serology was positive with high antibody levels and a Strongyloides IgG index of 4.1 (index ≥ 1 is a positive test, ≥ 2 is considered a high level). The colonic biopsies from the previous admission were re-examined and Strongyloides larvae were identified (Figure 1b).

The patient was administered 12 mg ivermectin tablets (0.2 mg/kg/day) once daily for a total of 20 days, i.e. 13 days after the first negative microscopic examination of faeces. At an outpatient check-up 3.5 months after discharge, the patient's condition was still improving, but due to elevation in eosinophils she was receiving another course of ivermectin, 9 mg on days 1 and 2, and days 14 and 15, which was the recommended treatment at that time. No larvae were observed on repeat microscopic examination of faeces, and neither were Strongyloides larvae detected in PCR testing. Follow-up serological testing after 6 and 12 months showed a significant decrease in antibody levels, indicating treatment success.