Currently, it’s estimated that one in 360,000 to one in 1 million people suffer from CAPS, with the majority having MWS or an overlap phenotype.7,8 NOMID/CINCA, although dramatic, is the least common of the CAPS phenotypes, numbering perhaps several hundred patients worldwide.5 The prevalence of FCAS is not clear, but most reported patients are from the U.S.
These figures, however, may be a substantial underestimate, in part due to varied clinical presentation, lack of awareness and difficulties in genetic diagnosis. In Israel, for example, there are 26 known patients with CAPS from a population of 8 million (~1:315,000), all diagnosed since 2007 [Note: PJH, personal knowledge], with nearly 50% of them belonging to the family previously described. Data from France indicate that since 2004, steady numbers of 4–12 new genetically proven, mostly sporadic cases are discovered yearly; most familial cases were diagnosed early after the discovery of the gene responsible for CAPS.8
Clinical Manifestations & Diagnosis
The three syndromes share many similarities, but differ in the severity of manifestations and, especially, in outcome.9 Common features include fever, urticaria-like rash, eye inflammation, musculoskeletal manifestation and headaches/central nervous system involvement. Table 1 (right) details the similarities and differences between the syndromes.
Patients may present to physicians from many specialties, including rheumatologists, pediatricians, internists, infectious disease specialists, allergists, immunologists, dermatologists, neurologists (and even neurosurgeons with hydrocephalus), ophthalmologists, otolaryngologists, orthopedists and neonatologists.10,11 In one series, 44% of patients were diagnosed with at least one other disease (as with the family in Case 2), and it took from 1.4 years (among infants born in the 21st century) to >30–40 years (adults born in the 1960s and 1970s) to be diagnosed.12,13 Prior to establishing the correct diagnosis, patients were diagnosed with—from the most frequent—conjunctivitis, other rheumatic disease, sensorineural hearing loss, urticaria and uveitis.13 Therefore, it’s extremely important that awareness of CAPS be spread to other specialists.
In potential patients, acute-phase reactants should be examined and if they are elevated without an adequate alternative explanation, CAPS (and possibly other autoinflammatory conditions) should be suspected.
There is often overlap between the three “classic” conditions, and as recently discovered, many patients may present atypically, further complicating disease recognition and diagnosis. For example, the frequency of rash in MWS varies in different series from 67–92%; thus, rash, although common and important, may not be a necessary feature in CAPS.8,12,13 One study reported significant differences in the presentation of CAPS in young children and adults, with recurrent fever and abdominal pain (i.e., inflammatory phenotype) much more frequent among children and general fatigue, musculoskeletal symptoms and hearing loss (without fever) in adults (i.e., organ-disease phenotype).12
