A rare cause of dysphagia and gastroparesis

Abstract

An 82-year-old woman was admitted with severe vomiting and progressive dysphagia mainly to solids. She gave a 3-month history of increasing heartburn, vomiting, tiredness, lethargy, anorexia and 13 kg weight loss. Her past medical history was unremarkable and she was a non-smoker. Physical examination revealed evidence of significant weight loss and dehydration only. Gastroscopy revealed mild oesophagitis, tongues of Barrett oesophagus and mild antral gastritis. CT scan of the thorax and abdomen was normal. Unfortunately her condition deteriorated rapidly and she died from aspiration pneumonia. Postmortem examination revealed thickening of the muscular wall of lower oesophagus and pylorus, but without any malignancy. The histological assessment of the oesophageal as well as gastric biopsies confirmed the diagnosis of gastrointestinal amyloidosis accounting for her symptoms of dysphagia and vomiting respectively.

BACKGROUND

Gastrointestinal (GI) tract involvement is common in systemic amyloidosis (postmortem studies show amyloid deposition in the GI tract in 70% to 100% of patients) but it causes symptoms in less than 1% of these patients. Our patient presented with symptomatic oesophageal and gastric amyloidosis in the absence of any pre-existing chronic medical conditions at the age of 82, which is very rare. The possibility of amyloidosis was not even in our differential diagnosis and the diagnosis was, unfortunately, made following the demise of the patient. Hence we have written this case report to alert our professional colleagues of the symptomatic presentation of GI amyloidosis, so that it can be considered in the differential diagnosis of patients with similar clinical presentation.

CASE PRESENTATION

An 82-year-old woman was admitted with severe vomiting and progressive dysphagia mainly to solids. She gave a 3-month history of increasing heartburn, vomiting, tiredness, lethargy, anorexia and 13 kg weight loss. Her past medical history was unremarkable and she was a non-smoker. Physical examination was unremarkable apart from the evidence of significant weight loss and dehydration.

INVESTIGATIONS

Blood tests revealed raised white cell count of 16 400 cells/mm³ (normal range 4000–11 000), urea 14.6 mmol/litre (2.5–8.5), creatinine 136 μmol/litre (65–130), alkaline phosphatase 167 U/litre (35–125), CRP 41 mg/litre (<10) with normal transaminases and a low albumin of 30 G/litre (35–55). Chest x ray was normal. Gastroscopy revealed mild oesophagitis, tongues of Barrett oesophagus (fig 1) and mild antral gastritis. There was evidence of food stasis in the stomach suggestive of underlying gastroparesis. The examination of pylorus and duodenum up to the second part was unremarkable. There was no evidence of any narrowing seen during gastroscopy to account for her symptoms.

Figure 1.

Endoscopic appearance of lower end of the oesophagus and cardia.

A CT scan of the thorax and abdomen was normal. Water-soluble oesophageal contrast swallow revealed significant bilateral bronchial aspiration and a static hold-up of the contrast at the gastro-oesophageal junction (GOJ) with smooth tapering without any shouldering (figs 2 and 3).

Figure 2.

Water-soluble contrast examination of the oesophagus (bilateral bronchial aspiration).

Figure 3.

Water-soluble contrast examination of the oesophagus (hold up of contrast at gastro-oesophageal junction (GOJ), arrow).

DIFFERENTIAL DIAGNOSIS

An underlying gastrointestinal malignancy was suspected.

TREATMENT

Despite proton pump inhibitor and antiemetic therapy, her vomiting and dysphagia worsened. She was kept nil by mouth and given total parenteral nutrition. Unfortunately her condition deteriorated rapidly and she died from aspiration pneumonia.

OUTCOME AND FOLLOW-UP

The postmortem examination revealed thickening of the muscular wall of lower oesophagus and pylorus, but without any malignancy. The histological assessment of the oesophageal (figs 4 and 5) as well as gastric biopsies confirmed the diagnosis of gastrointestinal amyloidosis.

Figure 4.

Histological assessment of oesophageal mucosa (haematoxylin and eosin stain, ×200).

Figure 5.

Histological assessment of oesophageal mucosa with Congo red stain (×200).

Figure 4 shows eosinophilic hyalinised tissue (arrow) in a blood vessel within the oesophageal wall, which showed positive staining with Congo red (arrow) (fig 5).

DISCUSSION

Amyloidosis is a group of diseases caused by extracellular deposition of abnormally folded, insoluble proteins. These aberrant proteins aggregate in various organs and tissues, leading to tissue dysfunction or organ failure. Rokitansky first described “lardaceous” change in viscera of patients with tuberculosis (TB) and malaria in 1842, but it was Virchow that first coined the term amyloid, 16 years later. Advances in electron microscopy allowed the structure to be further understood and in 1970, the amino acid sequence was derived.¹

All amyloid proteins stain positive with Congo red dye, stain pink with haematoxylin and eosin, and have apple-green birefringence under polarised light after Congo red staining. Historically they were classified mainly into primary (AL type, derived from immunoglobulin light chains as a result of plasma cell dyscrasia), secondary (AA type, caused by a chronic infection or inflammatory disease, eg, rheumatoid arthritis) and familial (derived from mutated transtherin protein in liver) forms.

The most recent classification is based on the biochemical structure of the fibril protein, A (amyloid). There are 23 distinct forms described; the most common are AA (amyloid A), AL (light chain) and AH (heavy chain).

Primary amyloidosis has an incidence of 8 per million per year, and the prognosis is poor, with a median survival of 13 months for those seen within a month of diagnosis.² The most common symptoms are fatigue and weight loss,³ often triggering a fruitless hunt for an occult malignancy. GI tract involvement is common in systemic amyloidosis (postmortem studies show amyloid deposition in the GI tract in 70% to 100% of patients)⁴ but less than 1% have GI symptoms. Submandibular swelling along with macroglossia and facial purpura are physical signs characteristic of amyloidosis; however, they are only seen in approximately 15% of patients with amyloidosis.³

GI symptoms often result from autonomic dysfunction. In the small and large bowel this manifests as malabsorption syndromes,^5,6 and in the oesophagus and stomach, it can produce dysmotility and gastroparesis respectively. Patients can also present with obstruction^7,8 or perforation.^9,10 Uniquely, our case has had evidence of symptomatic oesophageal as well as gastric dysmotility. Vascular occlusion by amyloid leading to gut ischaemia, infarction,¹¹ and haemorrhage,^12,13 has also been reported. Functional GI symptoms often result from either muscular or neuronal amyloidal infiltration or both. AA with predominant neuronal infiltration compared to extensive muscular infiltration in AL and AH has been shown to carry a better prognosis.¹⁴

Endoscopic appearances can be highly variable, ranging from inflammation to erosive disease, frank ulceration and even protuberant masses.¹⁵ This emphasises the importance of biopsies during gastroscopic examination in these patients.

If symptoms are suggestive of amyloidosis, electrophoresis and immunofixation of serum and urine are used as screening tests. For confirmation of the diagnosis tissue biopsy is required: subcutaneous fat aspirate or rectal biopsies are sensitive and convenient sites,³ although biopsy of the affected organ will establish a cause and effect relationship between the amyloid deposition and organ dysfunction. Serum amyloid protein (SAP) scan, using isotope labelled serum amyloid protein can be used to diagnose and monitor progression of amyloid deposition.¹⁶

The treatment of systemic amyloidosis remains a vital unmet need. The choice of treatment, systemic chemotherapy, stem cell transplantation or supportive therapy, depends on the type and extent of the disease. Supportive measures, including short-term or long-term parenteral nutrition, remain the mainstay of management of dysmotility of the GI tract. The nasogastric aspiration of the gastric contents in the presence of gastroparesis would be useful to prevent possible aspiration and might have prevented the aspiration pneumonia in our patient described above. A high index of suspicion is crucial if a diagnosis of amyloidosis is to be made early enough for treatment to avoid damaging, irreversible complications.

LEARNING POINTS

• In patients with recurrent dysphagia and/or gastroparesis with recurrent vomiting consider the diagnosis of gastrointestinal (GI) amyloidosis.

• Patients can present with amyloidosis in late age with no pre-existing chronic medical conditions.

• Early diagnosis and supportive nutritional measures are the key aspects of management GI amyloidosis.