High Prevalence of Autoantibodies Against Monomeric C Reactive Protein (CRP) in Children with PFAPA Syndrome.

PFAPA (periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis) syndrome is an autoinflammatory disorder of unknown etiology. The aim of our study was to evaluate whether the presence of anti-mCRP autoantibodies (anti-mCRP) might possibly contribute to systemic inflammation during PFAPA flares. We carried out anti-mCRP testing (in-house ELISA) in a single-center, prospective cohort of 30 PFAPA patients (12 girls). We found a high prevalence (43.3%) of anti-mCRP antibodies in PFAPA patients during their febrile episodes, which implies the possible involvement of anti-mCRP antibodies in PFAPA pathogenesis.

Mumps, measles and rubella vaccination in children with PFAPA syndrome.

There is no published data regarding immunologic response to vaccinations in children with PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis). The aim of this study was to evaluate mumps, measles and rubella immunity in children with PFAPA. 31 children with PFAPA syndrome and 22 healthy children (control group - CG) were recruited to the study. All children were previously vaccinated with one dose of MMR vaccine according to the Polish obligatory vaccination schedule. The patients from both groups were evaluated for anti-measles, anti-mumps and anti-rubella IgG antibodies concentrations (ELISA tests; the reference values for protective antibody levels were 150IU/L, 16RU/L and 11IU/ml respectively). The percentage of patients with protective antibodies levels was as follows: measles - 93.55% of PFAPA and 95.45% of CG patients (p=0.77); mumps - 74.19% of PFAPA and 95.45% of CG patients (p=0.02); rubella - 80.65% of PFAPA and 90.9% of CG patients (p=0.30). CONCLUSIONS: Children with PFAPA syndrome present a good response to the measles and rubella component of the MMR vaccine, however immunity against mumps after one dose of MMR may not be sufficient. Further investigation concerning immunity against vaccine-preventable diseases and the safety of vaccinations in children with periodic fever syndromes is required.

Procalcitonin and C-reactive protein-based decision tree model for distinguishing PFAPA flares from acute infections.

As no specific laboratory test has been identified, PFAPA (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis) remains a diagnosis of exclusion. We searched for a practical use of procalcitonin (PCT) and C-reactive protein (CRP) in distinguishing PFAPA attacks from acute bacterial and viral infections. Levels of PCT and CRP were measured in 38 patients with PFAPA and 81 children diagnosed with an acute bacterial (n=42) or viral (n=39) infection. Statistical analysis with the use of the C4.5 algorithm resulted in the following decision tree: viral infection if CRP≤19.1 mg/L; otherwise for cases with CRP>19.1 mg/L: bacterial infection if PCT>0.65ng/mL, PFAPA if PCT≤0.65 ng/mL. The model was tested using a 10-fold cross validation and in an independent test cohort (n=30), the rule's overall accuracy was 76.4% and 90% respectively. Although limited by a small sample size, the obtained decision tree might present a potential diagnostic tool for distinguishing PFAPA flares from acute infections when interpreted cautiously and with reference to the clinical context.

Polish consensus guidelines on the use of acyclovir in the treatment and prevention of VZV and HSV infections.

A physician has to perform a benefit-risk assessment each time acyclovir is prescribed "off label" for children. A group of Polish infectious disease experts was created to develop evidence-based guidelines on the use of acyclovir in the treatment and prevention of varicella zoster and herpes simplex infections. In primary varicella zoster virus infections, oral acyclovir treatment is recommended in children over 12 years of age and should be considered in younger children who fall into one of the groups at risk of severe varicella. Intravenous acyclovir therapy in varicella is recommended in patients with immune deficiencies, newborns and in complicated cases. When there is a justified need for prevention of varicella, oral acyclovir prophylaxis may be considered if immunoglobulin cannot be administered, and if it is too late for vaccination. Oral acyclovir treatment of herpes zoster may be beneficial to otherwise healthy patients with a rash in places other than the trunk and in patients over 50 years of age. In immunocompetent patients with herpes simplex infections, indications for treatment with oral acyclovir include primary (genital herpes, skin herpes in children with atopic dermatitis, ocular herpes simplex, severe gingivostomatitis, paronychia and pharyngitis) and recurrent infections. Intravenous acyclovir should be administered for herpes infections in neonates, immunocompromised patients and patients who develop complications including neurological.

Early Onset of Periodic Fever Syndrome in a Patient Carrying Both Tumor Necrosis Factor Receptor Superfamily 1A and Mediterranean Fever Mutations.

In this article, we report a nine-month-old male patient with a history of three unexplained, prolonged attacks of high fever, including one in the neonatal period, accompanied by an erythematosus, migratory rash. There was no family history that might have suggested a hereditary periodic fever syndrome, but the overall clinical picture was in accordance with tumor necrosis factor receptor-associated disease. Genetic analysis revealed two heterozygous mutations: C30Y in the tumor necrosis factor receptor superfamily 1A gene and K695R in the Mediterranean fever gene. This case shows that diagnosis of an autoinflammatory syndrome should be considered even in the youngest infants with incomplete presentation and no family history of recurrent fever.

The Pathogenesis of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome: A Review of Current Research.

BACKGROUND: PFAPA syndrome is a chronic disease that is characterized by recurrent episodes of high fever, aphthous stomatitis, pharyngitis, and cervical adenitis. Knowledge regarding the etiology of PFAPA is limited. OBJECTIVES: To provide up-to-date information considering etiology of PFAPA syndrome, by summarizing what has been explored and established in this area so far. MATERIALS AND METHODS: PubMed, Web of Science, and Scopus databases were searched for pertinent reports. Eventually 19 articles were selected. The results were classified into categories regarding three areas of interest: familial occurrence, genetic basis, and immunological mechanisms of PFAPA. RESULTS: Recent findings suggest that there is a familial tendency to PFAPA but the level of evidence does not warrant definite conclusions. The absence of a clear monogenic trait indicates a heterogenous, polygenic, or complex inheritance of PFAPA syndrome. As two mutations with a possible functional effect on the inflammasomes (MEFV E148Q and NLRP3 Q703K) have been found in several PFAPA cohorts, the role of inflammasome-related genes in PFAPA pathogenesis cannot be excluded. Immunological mechanisms of PFAPA involve an abnormal, IL-1ß dependent innate immune response to an environmental trigger, which leads to Th1-driven inflammation expressed by recruitment of T-cells to the periphery.