FMF is an autoinflammatory disease with autosomal recessive inheritance. Our patient presented homozygous E148Q mutation. E148Q is the most frequent variant among carriers, its pathogenic role is uncertain . In a recent analysis Topaloglu et al. demonstrated that patients homozygous for E148Q displayed typical FMF phenotype and half of these patients had moderate/severe disease before colchicine treatment .
Aydin et al. demonstrated that E148Q mutation is associated with a milder disease course, despite patients may have similar clinical findings and well response to colchicine therapy, when compared to patients with other mutations  . In our case, the patient presented recurrent fever episodes associated to abdominal, chest pain, and arthralgia and presented a good response to colchicine treatment.
It has been reported that E148Q mutation could induce a nonamyloidosis renal involvement. In particular Eroglu et al. described a case of mesangial proliferative glomerulonephritis in a woman affected by FMF with an heterozygous E148Q mutation . Ardalan et al. reported a case of an acute glomerulonephritis with proteinuria in a patient affected from FMF with an heterozygous E148Q mutation . Our patient presented persistent microalbuminuria 1 year later FMF diagnosis, so a renal biopsy was performed that revealed slight and irregular thickening of the lamina densa of some glomerular capillaries. This histopathological finding was compatible with diabetic nephropathy, so treatment with Ramipril was started .
Pyrin, the protein product of MEFV, is a 781-aminoacid protein expressed in serosal and synovial fibroblasts, granulocytes, and cytokine-activated monocytes.
The role of pyrin in IL-1 activation is controversial , Campbell et al. supposed that pyrin suppresses the activation of pro-caspase-1, by competing for ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain), and therefore pyrin interferes with NALP3 inflammasome activation . Chae et al demonstrated that Pyrin containing FMF-associated mutations has less of an inhibitory effect on the inflammasome, leading to upregulated synthesis of IL-1β .
T1D is a T-cell–mediated autoimmune disease characterized by the destruction of pancreatic beta cells in genetically predisposed individuals .
As in other autoimmune conditions, both innate and adaptive immunity play a role in disease pathogenesis [28, 29].
Kumar et al. demonstrated that T-helper type 17 (Th17) cells, have a pivotal role in T1D pathogenesis . Proinflammatory cytokine, in particular interleukin 1 (IL-1) and 6 (IL-6), are involved in differentiation of T-cells in Th17 . It has been demonstrated that TNFα, IL-1 and IL-6 are increased in diabetic subjects compared to control subjects at onset of clinical disease. These cytokine inducing differentiation of T-cells in Th17 are involved in T1D pathogenesis [31, 32].
Recent studies have demonstrated NLRP3 inflammosome and IL-1 iper-production could play an important role in the development of T1D in mice . The coexistence of FMF and type T1D is a rare finding. In 2006 Atabek et al. described a case of a 9 years old girl affected from T1D who developed FMF 11 months later diabetes onset . In 2009 Baş et al. reported a second patient with type T1D associated with FMF who also had autoimmune thyroid disease (ATD), celiac disease (CD) .
According to the recent progress in the understanding of T1D pathogenesis, in particular regarding the increase in serum levels of IL1 and IL6 at the onset of diabetes, we can suppose that the higher production of IL1 in FMF could be involved in development of T1D. Further studies or case series are needed to demonstrate this possible association.
Here we report the third association of FMF and T1D. FMF should be kept in mind in the differential diagnosis of disorders associated with T1D in the presence of recurrent and limited attacks of fever, associated with abdominal or chest pain or arthritis. The emerging role of the inflammatory cytokine (TNFα, IL-1 and IL-6)in the development of T1D adds a further dimension to our understanding of the multifactorial nature of the immunopathology that leads to the development of T1D but also opens a new area of research for potential therapy.