Aim:The syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) is a common inflammatory disease that presents with periodic fever.We aimed to establish more specific diagnostic criteria for PFAPA based on the clinical characteristics of PFAPA patients in our directory. Method:The clinical, laboratory, genetic, and family history details of 257 Japanese PFAPA patients treated at our and other affiliated hospitals between April 2000 and April 2018 were analyzed along with quantitative measurements of the number of CD64 molecules on neutrophils, and the levels of serum inflammatory cytokines. The sensitivity and specificity of the criteria were calculated for several diseases.Results: Because recurrent fevers were crucial findings, they were defined as the required criterion. Tonsillitis/pharyngitis with white moss were important accompanying signs. Other symptoms associated with febrile episodes were cervical lymphadenitis with tenderness, aphthous stomatitis, sore throat, vomiting, and headache but not cough. A total of 159 (62%) patients had a family history of recurrent fevers, indicating autosomal dominant inheritance. C-reactive protein levels were extremely elevated during febrile attacks but normal in attack-free periods. Serum immunoglobulin D levels were high in 72 of the 199 tested patients. Oral glucocorticoid and cimetidine were extremely effective in all and 51.6% of the patients, respectively. We defined the above as supportive criteria. These criteria were sensitive and specific enough to distinguish PFAPA from other recurrent fever diseases. Raised serum interferon-γ levels and remarkable CD64 expression on neutrophils during flare-ups were recognized, indicating they contributed to diagnosis. Conclusion:Our new criteria are useful for diagnosing PFAPA. K E Y W O R D S cytokine, diagnostic criteria, periodic fever, PFAPA, tonsillitis How to cite this article: Takeuchi Y, Shigemura T, Kobayashi N, et al. Clinical features and new diagnostic criteria for the syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis. Int J Rheum Dis.

Probucol was given to rats made diabetic by streptozotodn. Compared with diabetic rats not receiving probucol or with nondiabetic rats, probucol lowered the plasma concentrations of trigrycerkies, phospholipids, cholesterol, and apolipoproteln B. The concentrations of serum chylomicrons and very low density lipoprotein (VLDL) were also reduced. In control and diabetic rats, probucol enhanced the clearance of endogenoushy radiolabeled VLDL from the plasma. Clearances from the plasma of rat lymph chylomicrons or chylomicronlike lipkJ emulsions were slow in diabetic rats. Probucol normalized chyiomicron clearance in diabetic rats primarily by restoring hepatic uptake of remnants, which was decreased in diabetes. In diabetic rats, uptake of chyiomicron remnants was increased in a number of extrahepatic tissues, including the heart and kidney. Probucol significantly decreased uptake in some extrahepatic tissues. Increased plasma clearance of VLDL and chylomicrons was associated with an increase in the apolipoprotein CH/Clll and apolipoprotein E/C ratios. Orally administered probucol was specifically incorporated into lymph chylomicrons, and clearance of probucol from the plasma exactly paralleled the clearance of chyiomicron remnants, as traced with radiolabeled cholesteiyl esters. Chylomicron-like emulsions incorporating probucol were exclusively cleared from the plasma by the liver in normal rats. We conclude that in streptozotodn diabetic rats, probucol is an effective hypolipidemic agent because it promotes the clearance of the trigiyceride-rich lipoproteins. are frequently found in patients with diabetes mellitus. The hyperlipidemia primarily reflects slow clearance of plasma lipoproteins, although overproduction of lipoproteins may also be a contributing factor in non-insulin-dependent diabetes.1 A defective clearance from the plasma of chylomicrons and very low density lipoproteins (VLDLs) has been reported in human diabetic patients (for a review, see Howard 1 ) and in animal models of this disease.2 " 4 Hydrolysis of triglycerides may be compromised by severe insulin deficiency because insulin maintains the synthesis and secretion of lipoprotein lipase in some tissues.5 Posthydrolysis clearance of the remnant particles is also delayed, 6 although the reasons for this are unclear. Elevated plasma concentrations of triglycerides and cholesterol are thought to contribute to the high incidence of atherosclerosis in diabetic patients, and so it is desirable to reduce the concentrations of these lipids. Probucol is a potent hypolipidemic agent that reduces serum cholesterol level principally by increasing the fractional catabolic rate of low density lipoprotein (LDL). 7 ? Probucol is an effective lipid antioxidant, but it is not clear whether its pharmacological actions on the metabolism of LDL are related to the prevention of oxidation. Lipoproteins from diabetic donors show increased amounts of oxidative products compared with lipoproteins of nondiabetic origin. Probucol has been shown to decrease oxidation of...

Phosphatidylcholine (PC), especially dilinoleoyl-PC, has been reported to be effective in preventing hepatic fibrosis in chronically alcohol-fed baboons. Continuous hepatic inflammation predisposes the structure of the liver to fibrosis. Since n-3 polyunsaturated fatty acids (PUFA) have been shown to exhibit an anti-inflammatory effect, we tested the hypothesis that n-3 PUFA PC as a dietary supplement has a beneficial effect on chronic liver disease susceptible to fibrosis. Salmon roe phospholipids, 90% of which are PC, were extracted and encapsulated. Almost a third of the PC fatty acids were docosahexaenoic acid (22:6 n3) and 10% were eicosapentanoic acid (20:5 n3). About 1600 mg/day of the phospholipids was administered for six months to six chronic liver disease patients, four with hepatitis B infection (three with cirrhosis, one with chronic hepatitis), one with hepatitis C virus cirrhosis and one with alcoholic cirrhosis. There was no change in the results of blood chemistry studies related to liver function, except in globulin, which decreased from 3.80 g/dl to 3.67 g/dl (p < 0.05). Among the lipid parameters, HDL-cholesterol, apolipoprotein A-I and apolipoprotein E increased significantly. Although this was a small trial, n-3 PUFA PC may be beneficial in the treatment of chronic liver diseases.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most commonly encountered autoinflammatory disease in children, but its pathogenesis and diagnostic biomarkers are unknown. In this study, we examined the utility of CD64, a member of the Fcγ receptors, expressions on neutrophils and monocytes in diagnosing patients with PFAPA, along with other autoinflammatory diseases exhibiting periodic fever, and bacterial infections. Although CD64 was expressed at a similar level in the attack-free period of PFAPA and in controls, CD64 expressions on both neutrophils and monocytes were dramatically increased during attacks. Serum IFN-γ also increased in some PFAPA patients during flares, suggesting the involvement of T cell activation. Our findings demonstrate that remarkable CD64 expression during PFAPA flares serves as a potential biomarker for the diagnosis. We also suspect that IFN-γ, possibly from retention of activated T cells in peripheral tissues, increases CD64 synthesis in such cases.

The metabolism of oxidized chylomicrons (ox-CMs) was investigated in vivo. CMs from rats fed corn, linseed, or fish oil were oxidized by incubation with 2,2'-azobis(2-amidinopropane)hydrochloride (AAPH) or sodium hypochlorite (NaOCl). Oxidized CMs had a rapid phase of clearance, followed by a slow phase. Clearance of ox-CMs was decreased for corn oil but increased for linseed and fish oil particles. Differences in rats of uptake between CM types or treatment were independent of the rate of remnant formation, but were instead a consequence of decreased clearance. A greater triglyceride-to-cholesteryl ester ratio in liver suggested that there was less lipolysis of ox-CM triglyceride prior to uptake. Hepatic uptake of ox-CMs was decreased, whereas there was increased uptake in spleen. However, the uptake by Kupffer cells of ox-CMs was 43% of total liver uptake after AAPH treatment and 59% after NaOCl treatment, compared with 21% for control CMs. Collectively, our data show that oxidation can have differential effects on the rate of clearance of CMs and that ox-CMs are preferentially cleared by the reticuloendothelial system.