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but pleural effusion was never detected&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Since 2005&#44; he also mentioned pain with swelling in his hands&#46; This responded partially to treatment with ibuprofen&#44; as did the occasional arthralgia in knees and ankles&#46; He underwent genetic testing for FMF&#44; which detected an alteration on exon 10&#58; 2082G&#62;A mutation in a homozygote&#44; leading to a change to Met694Ile&#46; He began therapy with colchicine at a dose of 2<span class="elsevierStyleHsp" style=""></span>mg every 24<span class="elsevierStyleHsp" style=""></span>h&#44; and the number of attacks decreased&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">In 2013&#44; the number of episodes increased&#44; requiring maximum doses of colchicine&#44; with no clear improvement&#46; Physical examination revealed a rigid&#44; board-like abdomen&#44; with no other noteworthy finding&#46; A blood test only showed a mean corpuscular volume of 110<span class="elsevierStyleHsp" style=""></span>fL&#44; fibrinogen 366<span class="elsevierStyleHsp" style=""></span>g&#47;L and &#947;-glutamyl transpeptidase 79<span class="elsevierStyleHsp" style=""></span>IU&#47;L&#46; Systematic urinalysis&#44; serological tests&#44; a chest radiograph and abdominal ultrasound provided no evidence of disease&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">In December 2014&#44; the patient began with subcutaneous anakinra at a dose of 100<span class="elsevierStyleHsp" style=""></span>mg daily&#44; and has continued to take colchicine&#46; Since that time&#44; he has remained asymptomatic&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Resistance to colchicine is defined as 2 or more attacks each month while receiving the maximum dose&#46; This occurs in 5&#37;&#8211;10&#37; of patients with FMF&#44; although in some cases&#44; it may be due to poor treatment adherence&#46;<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1&#44;2</span></a> True cases of colchicine resistance are usually found in patients who are homozygous for the M694V&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The mechanism of action of agents that inhibit IL-1&#946; in the etiology and pathogenesis of this disease is well known&#46; The protein&#44; pyrin&#44; is a fundamental part of the so-called inflammasome&#44; the intracellular organelle necessary for the expression of IL-1&#946;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2&#44;4</span></a> which&#44; ultimately&#44; causes the patients&#8217; symptoms&#46; The IL-1&#946; inhibitors most widely used are anakinra&#44; rilonacept and canakinumab&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The biologic agent chosen for our patient was anakinra prescribed for compassionate use&#44; as it has achieved good responses in other inflammatory diseases&#44; such as rheumatoid arthritis and juvenile idiopathic arthritis&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Our patient continued to receive colchicine associated with the biologic therapy&#46; There is no consensus on that point in this respect&#58; logically&#44; it would be justifiable to discontinue it&#44; but some authors recommend maintaining it as an adjuvant therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> In this context&#44; the satisfactory response to the treatment was a sufficiently good reason to decide not to change the initial therapeutic proposal&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The uses of anakinra approved in Spain include the treatment of symptoms and signs of rheumatoid arthritis&#44; in combination with methotrexate&#44; in those patients who have not responded well&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> The secondary effects of this drug&#44; such as pruritus and erythema&#44; are infrequent and appear during the first 4 weeks&#46; There have been no reports of deaths due to severe opportunistic infection&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> Since 2006&#44; 22 studies have been published involving 64 patients from 10 different countries&#46; In all&#44; 76&#46;5&#37; of those treated with this drug achieve a complete response&#46; It has been ineffective in only 3 patients&#44; and the remainder had a partial response&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p></span>"
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Journal Information
Vol. 13. Issue 2.
Pages 120-121 (March - April 2017)
Vol. 13. Issue 2.
Pages 120-121 (March - April 2017)
Letter to the Editor
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Familial Mediterranean Fever Treated With Anakinra: A Case Report
Fiebre mediterránea familiar en tratamiento con anakinra: a propósito de un caso
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Javier Espíldora-Hernándeza,
Corresponding author
javiviespil@hotmail.com

Corresponding author.
, Manuel Abarca-Costalagob
a Servicio de Medicina Interna, Hospital Universitario Virgen de la Victoria, Málaga, Spain
b Servicio de Medicina Interna, Unidad Enfermedades Autoinmunes, Hospital Universitario Virgen de la Victoria, Málaga, Spain
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To the Editor,

The treatment of familial Mediterranean fever (FMF) has several objectives: achieving relief from the symptoms, preventing and managing acute attacks, and avoiding the development of secondary amyloidosis. Classically, the drug of choice is colchicine. Now, however, we also have interleukin 1β (IL-1β) inhibitors.

We report the case of a 37-year-old man, with no familial history or known allergies, who underwent appendectomy and had Ménière's disease in right ear. He began in 1996, at the age of 17 years, with fevers that peaked at up to 40°C, abdominal pain in right iliac fossa and occasional vomiting. These episodes lasted 2 or 3 days. He also customarily complained of pleuritic pain, but pleural effusion was never detected.

Since 2005, he also mentioned pain with swelling in his hands. This responded partially to treatment with ibuprofen, as did the occasional arthralgia in knees and ankles. He underwent genetic testing for FMF, which detected an alteration on exon 10: 2082G>A mutation in a homozygote, leading to a change to Met694Ile. He began therapy with colchicine at a dose of 2mg every 24h, and the number of attacks decreased.

In 2013, the number of episodes increased, requiring maximum doses of colchicine, with no clear improvement. Physical examination revealed a rigid, board-like abdomen, with no other noteworthy finding. A blood test only showed a mean corpuscular volume of 110fL, fibrinogen 366g/L and γ-glutamyl transpeptidase 79IU/L. Systematic urinalysis, serological tests, a chest radiograph and abdominal ultrasound provided no evidence of disease.

In December 2014, the patient began with subcutaneous anakinra at a dose of 100mg daily, and has continued to take colchicine. Since that time, he has remained asymptomatic.

Resistance to colchicine is defined as 2 or more attacks each month while receiving the maximum dose. This occurs in 5%–10% of patients with FMF, although in some cases, it may be due to poor treatment adherence.1,2 True cases of colchicine resistance are usually found in patients who are homozygous for the M694V.3

The mechanism of action of agents that inhibit IL-1β in the etiology and pathogenesis of this disease is well known. The protein, pyrin, is a fundamental part of the so-called inflammasome, the intracellular organelle necessary for the expression of IL-1β2,4 which, ultimately, causes the patients’ symptoms. The IL-1β inhibitors most widely used are anakinra, rilonacept and canakinumab.

The biologic agent chosen for our patient was anakinra prescribed for compassionate use, as it has achieved good responses in other inflammatory diseases, such as rheumatoid arthritis and juvenile idiopathic arthritis.5,6

Our patient continued to receive colchicine associated with the biologic therapy. There is no consensus on that point in this respect: logically, it would be justifiable to discontinue it, but some authors recommend maintaining it as an adjuvant therapy.7 In this context, the satisfactory response to the treatment was a sufficiently good reason to decide not to change the initial therapeutic proposal.

The uses of anakinra approved in Spain include the treatment of symptoms and signs of rheumatoid arthritis, in combination with methotrexate, in those patients who have not responded well.8 The secondary effects of this drug, such as pruritus and erythema, are infrequent and appear during the first 4 weeks. There have been no reports of deaths due to severe opportunistic infection.9 Since 2006, 22 studies have been published involving 64 patients from 10 different countries. In all, 76.5% of those treated with this drug achieve a complete response. It has been ineffective in only 3 patients, and the remainder had a partial response.10

References
[1]
A. Soriano, E. Verecchia, A. Afeltra, R. Landolfi, R. Manna.
IL-1β biological treatment of familial mediterranean fever.
Clin Rev Allergy Immunol, 45 (2013), pp. 117-130
[2]
Avi Livneh MD. Colchicine failure in familial mediterranean fever and potential alternatives: embarking on the anakinra trial. Available from: https://www.ima.org.il/FilesUpload/IMAJ/0/79/39873.pdf [accessed 16.12.15].
[3]
M. Lidar, H. Yonath, N. Shechter, F. Sikron, S. Sadetzki, P. langevitz, et al.
Incomplete response to colchicine in M694V homozygote FMF patients.
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Novel therapeutics for the treatment of familial Mediterranean fever: from colchicine to biologics.
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Dramatic beneficial effect of interleukin-1 inhibitor treatment in patients with familial Mediterranean fever complicated with amyloidosis and renal failure.
Nephrol Dial Transplant, 27 (2012), pp. 1898-1901
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M.L. Stoll, A.C. Gotte.
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Treatment of colchicine-resistant familial Mediterranean fever in children and adolescents.
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E. Ferris Villanueva, M. García Coronel, R. Guerrero Bautista.
Uso de anakinra en un caso de fiebre mediterránea familiar.
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V. Javadi Parvaneh, R. Shiari.
Treatment of colchicine-resistant familial Mediterranean fever with anakinra.
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Efficacy of anti-IL-1 treatment in familial Mediterranean fever: a systematic review of the literature.
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Please cite this article as: Espíldora-Hernández J, Abarca-Costalago M. Fiebre mediterránea familiar en tratamiento con anakinra: a propósito de un caso. Reumatol Clin. 2017;13:120–121.

Copyright © 2016. Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología
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