Autoinflammatory syndrome covers a set of disorders (the majority of which are hereditary) characterised by recurring and self-limiting episodes of inflammation, the result of inflammatory process control dysregulation. 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.

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.

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.

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,1–3 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.

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).4 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.5 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.

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.6 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+. Thus sacroiliitis is not the usual form of joint involvement in FMF, while oligoarthritis is with negative HLA-B27.7

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.

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.