Macroglossia+Heart Failure Symptoms+Low Voltage on ECG…Could this be amyloid?

Ben Kitchens gave an excellent Resident Update Talk today on amyloidosis and its management. Check out the slides below and key points:

  • Extracellular tissue deposition of fibrils composed of low molecular weight subunits of a variety of proteins
  • Point mutations, deletions, and premature stop codons may result in structural changes predisposing to fibril formation
  • Dr. Rudolph Virchow in 1854 first adopted the term “amyloid” to refer to tissue deposits of material that stained in a similar manner to cellulose when exposed to iodine
  • There are several forms of amyloidosis including AL, AA, dialysis-related, heritable, organ-specific
  • AL amyloidosis is the most common in the U.S. and is caused by the deposition of monoclonal light chains, more often λ than κ
  • Hepatic amyloid involvement has been reported in up to 90 percent of patients with AL amyloid
  • Diagnosis requires characteristic findings on tissue biopsy and evidence that the amyloid deposits are composed of clonal light chains
  • An abdominal fat pad aspirate or bone marrow biopsy may be positive in up to 80% of patients. If negative but suspicion remains high, then more invasive biopsy of clinically relevant tissue is needed
  • Amyloid deposits consist of amorphous eosinophilic material that demonstrates apple-green birefringence when stained with Congo red and viewed under polarized light
  • After a diagnosis is established, a cardiac assessment is critical, including electrocardiography and transthoracic echocardiography, which may show interventricular septal hypertrophy, restrictive physiology, and occasional “sparkling” changes in the myocardium
  • Cardiac involvement is associated with poorer prognosis
  • Treatment consists of melphalan and dexamethasone chemotherapy to eradicate the clonal plasma cells responsible for producing the pathogenic light chain. Autologous hematopoietic stem cell transplantation should be considered in younger patients without significant comorbidities
  • Patients with poor performance status, major comorbidities, involvement of three or more organs, and advanced cardiac amyloidosis are not considered transplant candidates
  • Bortezomib and lenalidomide regimens have also been used, particularly for relapsed disease

#clinicalpearls: Side Effects of Corticosteroids

  • Cardiovascular: sodium and fluid retention, hypertension
  • GI: Pancreatitis with high dose steroids, peptic ulcer
  • Neurologic: Psychosis, altered mood states, headaches, pseudotumor
  • Opthalmic: Posterior subcapsular cataracts, increased intraocular pressure, glaucoma, exopthalmos
  • Musculoskeletal: Osteoporosis, vertebral and femoral fractures, aseptic necrosis of femoral head, myopathy, muscle weakness
  • Endocrine: Diabetes mellitus/glucose intolerance, Cushingoid facies, hyperlipidemia, growth retardation, menstrual irregularities, suppression of pituitary-adrenal axis
  • Skin: Acne, increased bruising, impaired wound healing
  • Infectious: Increased risk of infections, including fungal

Pseudoachalasia

Introduction

Pseudoachalasia is a secondary form of achalasia which accounts for up to 4% of patients with achalasia-like syndrome, with symptoms, radiographic and esophageal manometric findings that mimic primary achalasia. It was first recognized by Ogilvie in 1947 as a form of achalasia due to involvement of the cardia region from gastric adenocarcinoma. Patients with idiopathic achalasia or pseudoachalasia can often be misdiagnosed as having other diseases, such as gastroesophageal reflux or stricture.

Causes of pseudoachalasia reported in the literature
Cause n (%)
Cardia-esophageal adenocarcinoma 156 (50)
Secondary malignancy 59 (19)
Benign lesions 45 (14)
Postoperative complications 35 (11)
Diseases of central nervous system 11 (3.5)
Paraneoplastic syndromes 7 (2.5)

Pathophysiology

Two patterns of tumor involvement have been described. The most common type consists of malignant stricture of the cardia which acts as a physical barrier to the passage of food. A less frequent type is strictly related to the malignant submucosal infiltration with secondary impairment of inhibitory neurons of the esophageal myenteric plexus by tumor cells. Another form of pseudoachalasia occurs following anti-reflux surgery. Three explanations have been proposed: misdiagnosed idiopathic achalasia with evidence of dysphagia just after surgery, achalasia occasionally developing for the underlying gastroesophageal reflux, and development of scar tissue and/or an overly tight fundic wrap.

Diagnosis

Pseudoachalasia needs to be excluded in older patients (> 60 years) with a short duration of symptoms (< 1 year) and substantial weight loss. It might be difficult to diagnose in an early phase, because of the purported low diagnostic yield of barium and endoscopy studies. Endoscopic ultrasound can provide information regarding the level of tumor invasion and possible spread to regional lymph nodes, but shows a low accuracy in differentiating mucosal from submucosal lesions at the lower esophagus or gastroesophageal junction and only repeated studies or even surgical exploration may point to the diagnosis of pseudoachalasia. Esophageal manometry remains the current gold standard to diagnose esophageal motor disorder, both in idiopathic achalasia and pseudoachalasia, which includes an abnormal relaxation of the LES and absence of peristalsis in the esophageal body.

Pseudo v achalasia

Management

Since the major mechanism of pseudoachalasia is mechanical obstruction of the distal esophagus, the removal of this obstruction either by surgery, chemotherapy, and/or radiation can be the goal of treatment in some cases. It often allows the return of normal peristalsis into the esophagus. However, in many patients with pseudoachalasia, the esophageal motor abnormalities can remain even after a radical treatment of the neoplasia. The use of expandable metal stents has been proposed as an additional therapeutic option in selected cases of pseudoachalasia when palliation is required in patients not suitable for surgery.

Adapted from: World J Gastrointest Endosc.2013 September 16; 5(9): 450-454. Published online 2013 September 16. doi: 10.4253/wjge.v5.i9.450. Published under the Creative Commons license.