FMF is the paradigm of the periodic fever syndromes. It is an autosomal recessive (AR) disorder due to mutations in the gene MEFV (MEditerranean FeVer), which encodes a protein named pyrin or marenostrin [2, 3]. Pyrin is a main regulatory component of the NLRP3 inflammasome, a large protein complex that takes part in inflammation signaling pathways such as the IL-1β pathway [4].

FMF patients present episodic attacks of fever that typically last less than 72 h, abdominal pain, pleurisy, mono or oligoarticular arthritis, and/or arthralgias [5]. Attacks are self-limited and between them the patient remains asymptomatic. The interval between attacks is variable. Exercise, emotional stress, exposure to extreme temperatures, and hormonal changes can trigger the attacks [5]. Amyloidosis is a severe complication that could appear in untreated patients. Erysipeloid-like lesions, which appear in 15–20 % of children, are the characteristic cutaneous manifestation of FMF [6–8]. They usually appear in the lower extremities as well-circumscribed edematous and erythematous plaques. Histopathology shows a predominantly neutrophilic infiltrate with nuclear dust [9]. Purpuric lesions on the face, trunk, and extremities have also been reported in children.

Colchicine is the treatment of choice; it reduces the frequency, intensity, and the duration of the attacks [10]. In patients who do not respond to colchicine, it is important to verify the compliance with therapy. Intravenous colchicine could be tried as some of these not-responders do respond to this regime. There are isolated reported cases of truly colchicine-resistant patients that responded to thalidomide, to anti-TNFα agents such as etanercept and infliximab, and to the recombinant IL-1 receptor antagonist anakinra [11, 12].

CAPS include familial cold autoinflammatory syndrome (FCAS, or familial cold urticaria), Muckle–Wells syndrome (MWS, urticaria-deafness-amyloidosis syndrome), and neonatal onset multisystemic inflammatory disorder (NOMID, also named as chronic infantile neurological cutaneous and articular (CINCA) syndrome). NOMID is the most severe form of CAPS. Symptoms appear shortly after birth, usually before 6 months of age. The triad of fevers, skin urticarial rash, severe arthropathy, and central nervous system disorders characterizes NOMID [14, 15] (Fig. 43.1). Patients with NOMID show abnormal facial features, including flattening of the nasal bridge, macrocephaly, frontal bossing, and protruding eyes [16]. Neurological manifestations develop with time, and include chronic aseptic meningitis, cerebral atrophy, sensorineural hearing loss, and developmental delay. Eye manifestations, such as anterior uveitis, papilledema, or blindness, also occur in NOMID [17]. About 50 % of patients have severe arthropathy before 12 months of age. Secondary amyloidosis may appear due to chronic inflammation [1]. An erythematous skin eruption resembling urticaria is usually present in the neonatal period or may appear before 6 months of age. The rash persists during the whole life of patients. On histopathology, superficial and deep perivascular infiltrates are seen composed mainly of neutrophils, lymphocytes, and some eosinophils [18].

Anakinra, the IL-1 receptor antagonist, has shown dramatic improvement of CAPS, although not all patients respond equally [19]. Rilonacept and canakinumab can achieve complete and sustained responses in almost all cases of CAPS [19].