Letter to the Editor
Atypical familial Mediterranean fever with PFAPA-Like symptoms and psoriasis
Variante atípica PFAPA-like de la fiebre mediterránea familiar asociada a psoriasis
a Unidad de Diagnóstico Médico y Enfermedades Minoritarias, Servicio de Medicina Interna, Hospital Universitario de Torrevieja, Torrevieja, Alicante, Spain
b Servicio de Reumatología, Hospital Universitario de Torrevieja, Torrevieja, Alicante, Spain
c Servicio de Alergia, Hospital Universitario de Torrevieja, Torrevieja, Alicante, Spain
d Servicio de Medicina Interna, Hospital Quirón Torrevieja, Torrevieja, Alicante, Spain
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Clinically it is not easy to differentiate one entity from another, and atypical forms that simulate other processes also exist within clearly defined entities. Genetic diagnostic techniques will help us to improve our knowledge of these entities.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Within this context we describe the case of a 70 year-old woman who was referred to study recurring episodes of pharyngeal angioedema and fever. The first symptoms appeared at the age of 4 years, with recurring and self-limiting episodes of fever, pharyngitis, adenopathies and crises of abdominal pain. These symptoms were attributed to viral infections. The pharyngeal symptoms improved in adolescence, although the fever and abdominal crises persisted, with the addition of joint symptoms. At 58 years old she was diagnosed with cutaneous psoriasis and psoriatic oligoarthritis, without signs in MR imaging of spondyloarthritis or sacroiliitis, with negative HLA-B27. Treatment commenced with leflunomide. Symptoms have worsened in recent years, with weekly episodes.</p><p id="par0015" class="elsevierStylePara elsevierViewall">There was no sign of eosinophilia in the haemogram. Routine biochemical analyses were normal. Electrophoresis, immunoglobulins A, G, M, D and E, complement levels, ANA, cryoglobulins, tryptase, HIV, HBV and HCV were normal or negative. Given the suspicion of an autoinflammatory syndrome a genetic study was requested, focussing on 109 genes involved in autoinflammatory processes. Heterzygotic alterations were only found in the germ line that involved the MEFV E148Q gene (exon 2)/P369S and R408Q (exon 3). Based on these data the diagnosis of atypical variant familial Mediterranean fever (FMF) was established, Aphthous stomatitis, Pharyngitis and Adenopathy (PFAPA)-like.</p><p id="par0020" class="elsevierStylePara elsevierViewall">A typical attack of FMF is defined as an episode lasting from 12 h to 3 days, with fever accompanied by peritonitis, pleuritis or monoarthritis. Nevertheless, atypical variants have been described, one of which is similar to PFAPA syndrome. The 8 cases published in the literature on this variant,<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1–3</span></a> like our case, describe episodes of fever associated with pharyngitis, cervical lymphadenopathy and tonsillitis. In 7 of these 8 cases it is associated with the E148Q/P369S/R408Q variant, while in the other case it is associated with P369S/R408Q. Only one previously published case of this FMF variant had abdominal pain and, as in our case, it was associated with the E148/P369S/R408Q variant of the MEFV gene.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The second point to be considered is superimposition with other autoinflammatory syndromes. An increase in the frequency of psoriasis in patients with FMF has been described in this context, especially in the adult population (OR of 16.34, and an incidence of 3.7% in comparison with 0.42% of the general population).<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> The mechanism shared by both processes would be the action of IL-1. The purine produced in FMF causes an increase in the levels of IL-1, which plays an essential role in the early signalling of Th17 lymphocytes. Ashida et al.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> have demonstrated that active Th17 lymphocytes are present in the dermis of FMF patients with similar lesions to those present in cutaneous psoriasis. These lymphocytes stimulate keratinocytes.</p><p id="par0030" class="elsevierStylePara elsevierViewall">In the few studies that exist, the presence of psoriasis has chiefly been associated with the M694V and 680I variants in homozygosis and heterozygosis, and there is only one case of an E148Q variant in heterozygosis, this being the variant of our patient.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> Respecting oligoarthritis, Kaşifoğlu et al. describe this in 27% of patients with clinical musculoskeletal FMF, although only 7% of the total number of patients have sacroiliitis, which in 94% of cases is associated with the M694V mutation, and in 47% of cases with HLA-B27<span class="elsevierStyleSup">+</span>. Thus sacroiliitis is not the usual form of joint involvement in FMF, while oligoarthritis is with negative HLA-B27.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Treatment with colchicine and corticoids is only partially beneficial, so that treatment with anakinra is proposed for this variant, a human IL-1 receptor antagonist. After 2 months of treatment the patient has progressed from suffering a crisis every week to not having any crises.</p><p id="par0040" class="elsevierStylePara elsevierViewall">To conclude, there are atypical forms of FMF. In patients with recurring episodes of pharyngitis, stomatitis and lymphadenopathies, the possibility of an autoinflammatory syndrome should be taken into account, especially if they are accompanied by abdominal pain or monoarthritis.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Blasco F, García A Á, Martos MD, Muñoz S. Variante atípica PFAPA-<span class="elsevierStyleItalic">like</span> de la fiebre mediterránea familiar asociada a psoriasis. 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Cansu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10067-008-0980-3" "Revista" => array:6 [ "tituloSerie" => "Clin Rheumatol" "fecha" => "2009" "volumen" => "28" "paginaInicial" => "41" "paginaFinal" => "46" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18795391" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735743/0000001700000008/v1_202110061021/S2173574320301404/v1_202110061021/en/main.assets" "Apartado" => array:4 [ "identificador" => "8400" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735743/0000001700000008/v1_202110061021/S2173574320301404/v1_202110061021/en/main.pdf?idApp=UINPBA00004M&text.app=https://www.reumatologiaclinica.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574320301404?idApp=UINPBA00004M" ]
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| 2023 March | 55 | 29 | 84 |
| 2023 February | 44 | 35 | 79 |
| 2023 January | 53 | 20 | 73 |
| 2022 December | 68 | 29 | 97 |
| 2022 November | 91 | 40 | 131 |
| 2022 October | 78 | 33 | 111 |
| 2022 September | 81 | 25 | 106 |
| 2022 August | 216 | 54 | 270 |
| 2022 July | 201 | 51 | 252 |
| 2022 June | 43 | 37 | 80 |
| 2022 May | 48 | 48 | 96 |
| 2022 April | 64 | 54 | 118 |
| 2021 September | 1 | 1 | 2 |
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