Amyloidosis is deposition of abnormal extracellular insoluble proteins (linked to glycosaminoglycan, serum amyloid P and proteoglycans), it could be localized and systemic in different tissues and organs which can lead to cause multiple organs dysfunction .It can be classified also as acquired or hereditary in addition to other classification depend on the cause of amyloid deposition [1]. Major form of amyloidosis include [2]:

• AL Amyloidosis- derived from immunoglobulin light chain fragment deposition

• Transthyretin amyloidosis (ATTR)-associated with familial or non-familial forms 

• AA amyloidosis the most common form in resource limited countries complicate chronic inflammation and infection

• Dialysis-related amyloidosis 

• Heritable amyloidosis

• Organ specific amyloid             

Clinical features vary depending on the distribution of deposition and type of amyloid. Features that suggest amyloidosis include waxy skin, easy bruising, enlarged muscles, cardiomyopathy, hepatomegaly, heavy protein urea and neuropathy [2] .The kidneys are the most frequently involved organ in 70 to 80 % of patients. Patients with liver involvement usually developed cholestasis with an elevated alkaline phosphatase with minimal aminotransferases alteration and preservation of synthetic function [3]. Diagnosis depend on tissue organ involved tissue biopsy. Fat pad biopsy is the essential biopsy technique in systemic amyloidosis while in localized amyloidosis, biopsy of the involved organ is recommended [2].     

No satisfactory treatment for systemic amyloidosis has been discovered and mean survival is poor [1]. In those with suspected with hepatic amyloidosis, a subcutaneous fat aspirate or a bone marrow biopsy are usually positive(80% and 82% respectively),providing a diagnostic alternative  to live biopsy, which may carry an increased bleeding risk from hepatic amyloid infiltration. Hyperbilirubenemia is associated with a poor prognosis. The majority of deaths are related to cardiac or renal complications or, in the case of multiple myeloma, to progression of the underlying malignancy [4]. 

Hussein Shreef, 60-year man previously healthy, presented for 3 months with abdominal distention, anorexia, decrease appetite, weight loss 5Kg and fatigue. He didn’t have malena or hematemesis 

On Examination: 

Hussein was conscious, oriented, looks pale, no yellowish discoloration of sclera, no cyanosis, had multiple skin bruises over his left arm and leg, no other abnormal skin pigmentation. 

Heart and lung examination were normal.

Massive hepatomegaly live span 20cm and enlarge Spleen. He didn’t have macroglossia or peripheral neuropathy 

Vital Signs 

• Bp 120/70 mmHg

• PR 82 Bpm regular 

• Temp. 37 C

Investigation

CBC shows WBC 9.1x10³/L, HB 10.1 g/dl, MCV 107.1 fl, platelets 374x103/ML Blood film shows normal WBC and platelets morphology with macrocytic RBC RFT shows blood urea 75.9 mg/dl, serum creatinine 1.039 mg/dl, ALT, AST and bilirubin were normal  ALP 422 U/L HBV, HCV, HIV are negative  PT 13.6 sec, INR1.1, PTT 40.1 sec GUE shows 25 RBC cell/uL, protein 1 g/L , no WBC 24hr urine protein 5950 mg/24 hr ACR 135.1 mg/g ECHO study shows mild LVH (IVS 13 mm) Abdominal ultrasound examination shows liver is enlarged (20 cm), normal texture, no SOL, normal PV Spleen is enlarged 15 cm, no ascites. Both kidneys are normal in size. 

Serum protein electrophoresis shows increase alpha 1 and gamma globulins OGD shows GERD and duodenopathy. Colposcopy shows nodular rectum apart from normal colon Duodenal biopsy revealed mucosal inflammation with focal villous distortion 

Rectal biopsy reveled mild mucosal edema and inflammation, no malignancy.

Figure 1: Abdominal Fat Pad biopsy (H&E stain), showing deposition of a cellular homogenous pinkish material

Figure 2: Abdominal Fat Pad biopsy, Congo red stain, showing positive staining

Congo red stain is negative of duodenal and rectal biopsy Abdominal Fat Pad biopsy shows fatty tissue with deposition of a cellular homogenous pinkish material, Congo red stain is positive.

Co-existence of renal, hepatic, skin, heart and peripheral neurons practically in combination with nonspecific symptoms such as fatigue and weight loss should raise suspicion of amyloidosis and prompt specific investigation. In AL and AA amyloidosis the major sites of clinically important amyloid deposition are in the kidneys, heart and liver whereas in ATTR amyloidosis, heart and nervous system involvement predominate.

Patient with biopsy documented amyloidosis and plasma cell dyscrasia need not undergo further testing for an underlying hematological disorder.

Patients without a known plasma cell disorder should be tested to determine whether a monoclonal protein is present in serum, urine, or both using a serum and urine protein electrophoresis, followed by immunofixation 
 

1. Hobson, Richard. Davidson’s Principles and Practice of Medicine. 23rd ed., p. 81.

2. Gorevic, Peter D., and Helen J. Lachmann. “Overview of Amyloidosis.” UpToDate, https://www.uptodate.com/contents/overview-of-amyloidosis.

3. Jameson, J.L., et al.. Harrison’s Principles of Internal Medicine. 20th ed., p. 803.

4. Feldman, Mark, et al.. Sleisenger & Fordtran’s Gastrointestinal and Liver Disease. 11th ed., vol. 2, pp. 556–557.