Rheumatology Advance Access originally published online on July 31, 2006
Rheumatology 2006 45(10):1307-1308; doi:10.1093/rheumatology/kel250
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
LETTERS TO THE EDITOR |
Clinical improvement with infliximab in a child with amyloidosis secondary to familial Mediterranean fever
nkayaDepartment of Paediatric Nephrology, Ankara University School of Medicine, Ankara, Turkey
Correspondence to: F. Yalçnkaya, Ankara Universitesi Tip Fakultesi Cebeci Hastanesi, Cocuk Nefroloji Bilim Dal, 06100 Dikimevi, Ankara, Turkey. E-mail: yalcinkaya{at}tr.net
SIR, The most serious and fatal complication of familial Mediterranean fever (FMF) is amyloid A (AA) amyloidosis, usually affecting the kidneys, resulting in renal insufficiency progressing to end-stage renal disease. Amyloidosis may also affect the gastrointestinal tract, liver, spleen and other organs. Here, we present a case of FMF complicated by protracted arthritis, severe renal and gastrointestinal amyloidosis in which treatment with infliximab is associated with the clinical improvement of amyloidosis, in addition to complete resolution of protracted arthritis.
A 12-yr-old girl was admitted to the hospital with bloody diarrhoea, vomiting, nephrotic syndrome, intermittent bilateral knee pain and swelling. Past medical history revealed recurrent attacks of abdominal pain and fever since the age of five. From 8 yrs of age, she had been suffering from recurrent arthritic attacks of the knees and ankles accompanied with fever and had been treated with antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids and methotrexate with the presumed diagnosis of septic arthritis, acute rheumatic fever (ARF) and juvenile rheumatoid arthritis (JRA). She had worsened despite these therapies; 1 yr before her first admission, Mediterranean fever mutation test showed compound heterozygous for M694V/M680I mutations and colchicine therapy was started. However, she had discontinued the drug because of vomiting and diarrhoea. Swelling of the lower extremities and face developed 3 months before her first admission. She was the second child of first degree cousins and she had no family history of FMF. On admission, she had pallor, oedema, marked ascites and protracted arthritis of the knees. Her height and weight values were below the third percentile for age and sex. She couldn't walk. She had mild anaemia, massive proteinuria and severe hypoalbuminaemia. Acute phase reactants were elevated, renal function tests and other biochemical parameters were normal. Renal, rectal and duodenal biopsies revealed AA amyloidosis confirmed by Congo red stain and by immunohistochemical staining. Colchicine 2 mg/day was restarted and naproxen therapy was commenced. However, she experienced no improvement in symptoms. She had no appetite and experienced a weight loss of 4 kg in a month because of recurrent abdominal pain, vomiting, diarrhoea and associated fever. The requirements of hospitalization and albumin infusions increased. In November 2003, a trial of infliximab 3 mg/kg was initiated at 0, 2 and 6 weeks and then every 8 weeks. By the fifth dose of infliximab, the patient felt dramatically better (Table 1). Diarrhoea and arthritis improved significantly during the following months. She did not receive any albumin infusions after the onset of infliximab therapy. The patient was able to return to school after 2 yrs of disability secondary to arthritis and diarrhoea. After 22 months of therapy, gastrointestinal complaints resolved completely and protracted arthritis improved. She could walk and even run without any difficulty. In addition to these clinical findings laboratory markers improved markedly (Table 1).
|
Amyloidosis, the potentially lethal complication of FMF, is known to be prevented by effective dose regular colchicine therapy. However, it was unfortunately shown that the patients with severe nephrotic syndrome will progress to chronic renal failure, in spite of colchicine treatment [1, 2]. There is still no alternative therapy to prevent this progression.
There have recently been several reports that anti-tumour necrosis factor (TNF) agents may affect amyloidosis in familial auto-inflammatory disease such as tumour necrosis factor receptor-associated periodic syndrome (TRAPS) and other chronic inflammatory diseases such as rheumatoid arthritis (RA) and ankylosing spondylitis [3–7]. Drewe et al. [3, 4] reported clinical efficacy of etanercept in three patients with TRAPS and AA amyloidosis in two different reports. Elkayam et al. [5] described a case of RA complicated by renal amyloidosis in which treatment with infliximab was associated with complete resolution of proteinuria and stabilization of amyloid deposits in 2002. Two preliminary studies from France and Spain indicated that anti-TNF therapy might be useful in amyloidosis secondary to inflammatory arthropathies [6, 7]. In addition, two recent reports have shown that anti-TNF therapies were used successfully in the patients with FMF and chronic arthritis [8, 9]. Finally, Metyas et al. [10] described the resolution of amyloid-related arthritis and an improvement of renal involvement in a patient with amyloidosis secondary to FMF with anti-TNF therapy. Our patient had amyloid deposition on biopsies obtained from gastrointestinal tract and kidney. Infliximab was started for protracted arthritis. While protracted arthritis resolved completely, her gastrointestinal symptoms due to amyloidosis disappeared. Moreover, her proteinuria decreased and the requirement of albumin infusion therapy disappeared. Her quality of life clearly improved after the use of infliximab treatment.
Although the results of our patient yield a promising role of infliximab treatment in FMF-associated amyloidosis, further clinical studies are necessary to elucidate the long-term safety and efficacy of this treatment.
The authors have declared no conflicts of interest.
 |
References |
|---|
 Top References |
|---|
- Zemer D, Livneh A, Danon YI. (1991) Long term colchicine treatment in children with FMF. Arthritis Rheum 34:973–7.[ISI][Medline]
- Cakar N, Yalcinkaya F, Ozkaya N, et al. (2001) Familial Mediterranean fever (FMF)-associated amyloidosis in childhood. Clinical features, course and outcome. Clin Exp Rheumatol 19:Suppl 24, 63–7.
- Drewe E, McDermott EM, Powell RJ. (2000) Treatment of the nephrotic syndrome with etanercept in patients with the tumor necrosis factor receptor-associated periodic syndrome. N Engl J Med 343:1044–5.
[Free Full Text] - Drewe E, Huggins ML, Morgan AG, Cassidy MJ, Powell RJ. (2004) Treatment of renal amyloidosis with etanercept in tumour necrosis factor receptor-associated periodic syndrome. Rheumatology 43:1405–8.
[Abstract/Free Full Text] - Elkayam O, Hawkins PN, Lachmann H, Yaron M, Caspi D. (2002) Rapid and complete resolution of proteinuria due to renal amyloidosis in a patient with rheumatoid arthritis treated with infliximab. Arthritis Rheum 46:2571–3.[CrossRef][ISI][Medline]
- Gottenberg JE, Merle-Vincent F, Bentaberry F, et al. (2003) Anti-tumor necrosis factor alpha therapy in fifteen patients with AA amyloidosis secondary to inflammatory arthritides: a followup report of tolerability and efficacy. Arthritis Rheum 48:2019–24.[CrossRef][ISI][Medline]
- Fernandez-Nebro A, Tomero E, Ortiz-Santamaria V, et al. (2005) Treatment of rheumatic inflammatory disease in 25 patients with secondary amyloidosis using tumor necrosis factor alpha antagonists. Am J Med 118:552–6.[CrossRef][ISI][Medline]
- Daysal S, Akcil G, Goker B, Haznedaroglu S, Ercan N, Ozturk MA. (2005) Infliximab therapy in a patient with familial Mediterranean fever and chronic hip arthritis. Arthritis Rheum 53:146–7.[CrossRef][ISI][Medline]
- Ozgocmen S, Ozcakar L, Ardicoglu O, Kocakoc E, Kaya A, Kiris A. (2006) Familial Mediterranean fever responds well to infliximab: single case experience. Clin Rheumatol 25:83–7.[CrossRef][ISI][Medline]
- Metyas S, Arkfeld DG, Forrester DM, Ehresmann GR. (2004) Infliximab treatment of Familial Mediterranean fever and its effect on secondary AA amyloidosis. J Clin Rheumatol 10:134–7.[CrossRef][ISI][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||