A domestic fight or something else?

(Section Editor: T. J. Rabelink)

Jan Maarten van Woerkom and D. Willem van Toorn

Department of Internal Medicine, Gelre Ziekenhuizen, location Lukas Hospital, 7300 DS APELDOORN, The Netherlands.

A 53-year-old woman without significant medical history was admitted to our outpatient clinic with recurrent haemorrhages in the peri-orbital region of both eyes (Fig. 1Go). This patient was sent by the ophthalmologist who had found no intra-orbital lesions. The haemorrhages occurred spontaneously approximately three times a month without preceding trauma. On physical examination no abnormalities (in particular no haemorrhages) were observed. Laboratory investigation revealed normal platelet counts and no clotting disorders were found.



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Fig. 1. Patient with haemorrhages in the peri-orbital region of both eyes.

 
Three years later she presented with pitting oedema in both legs. She said this oedema occurred or was aggravated by eating products rich in animal protein. On examination, no other abnormalities were observed. Her blood pressure was 130/70 mmHg. Serum albumin was 17 g/l. There were normal values for serum creatinine and BUN. The urine sediment was normal but there was a proteinuria of 5.0 g/l. The selectivity-index was 0.12, suggesting loss of only small protein molecules.

A diagnostic procedure was performed.

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A biopsy of the kidney showed granular mesangial depositions which stained positive for Congo red, suggesting these depositions to be amyloid fibrils. These depositions could also be seen in the HE-section (Fig. 2Go). There were no observations suggestive of a glomerulonephritis. There only was a small amount of focal glomerulosclerosis.



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Fig. 2. Amyloid fibril depositions seen in HE-section.

 
The diagnosis primary (AL) amyloidosis could be made based on peri-orbital ecchymoses, nephrotic syndrome and amyloid depositions in the kidney.

Peri-orbital ecchymoses in AL amyloidosis is called ‘raccoon eyes’ or ‘raccoon syndrome’ [1,2], and is caused by vascular infiltration of amyloid fibrils in peri-orbital blood vessels. These ecchymoses may occur spontaneously (as in our patient) or after minimal trauma such as sneezing or rubbing the eyes. ‘Raccoon eyes’ are rather specific for AL amyloidosis. Other causes of peri-orbital bleeding include clotting disorders, essential thrombocytaemia and trauma. There is no consequence for the vision as there is no intra-ocular problem.

In the treatment of AL amyloidosis, chemotherapy consisting of melphalan and prednisolone may be considered [3,4] in patients with an adequate pre-treatment performance status. Combination therapy of intravenous melphalan and autologous haematopoetic cell transplantation may be of benefit in patients with involvement of fewer than two major organ systems, uncomplicated cardiac symptomatology and patients younger than 50 years [5]. Successful treatment with the iodinated anthracycline 4'-iodo-4'-deoxydoxorubicin has also been described [6]. There is no specific treatment for the ‘raccoon eyes’. Reduction of the proteinuria might be achieved using ACE-inhibitors [7] or NSAIDS [8].

Unfortunately, during the last 2 years our patient was admitted several times because of dyspneu and oedema of all extremities. Chest radiographs showed pleural effusions. Treatment with diurestics, an angiotensin-II-receptor antagonist and cyclosporin has not been very successful, she needs high doses of loop-diuretics to prevent increase of pleural effusions. Moreover, there is a subjective intolerance to most drugs resulting in poor compliance.

Notes

Supported by an educational grant from

Suggested reading

  1. Falk RH, Comenzo RL, Skinner M. The systemic amyloidoses. N Engl J Med1997; 337: 898–909[Free Full Text]
  2. Sipe JD, Cohen AS. Amyloidoses. In: Harrison's principles of internal medicine. CD-ROM 14th edition
  3. Skinner M, Anderson JJ, Simms R et al. Treatment of 100 patients with primary amyloidosis: a randomized trial of melphalan, prednisone and colchicine versus colchicine only. Am J Med1996; 100: 290–298[ISI][Medline]
  4. Kyle RA, Gertz MA, Greipp PR et al. A trial of three regimens for primary amyloidosis: colchicine alone, melphalan and prednisone, and melphalan, prednisone, and colchicine. N Engl J Med1997; 336: 1202–1207[Abstract/Free Full Text]
  5. Comenzo RL. High-dose therapy for the treatment of primary systemic amyloidosis. Hematology 1999: Education Program Book of the American Society of Hematology1999: 347–356
  6. Gianni L, Belotti V, Gianni AM, Merlini G. New drug therapy of amyloidosis: resorption of AL-type deposits with 4'-iodo-4'-deoxydoxorubicin. Blood1995; 86: 855–861[Abstract/Free Full Text]
  7. Gansevoort RT, Sluiter WJ, Hemmelder MH, de Zeeuw D, de Jong PE. Antiproteinuric effects of blood-pressure-lowering agents: a meta-analysis of comparative trials. Nephrol Dial Transplant1995; 10: 1963–1974[Abstract]
  8. Arisz L, Donker AJM, Brentjens JRH, van der Hem GK. The effect of indomethacin on proteinuria and kidney function in the nephrotic syndrome. Acta Med Scand1976; 199: 121–125[ISI][Medline]




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