PFAPA syndrome: new clinical aspects disclosed

Background

The recently described PFAPA (Periodic Fever, Aphthous stomatitis, Pharyngitis and Adenitis) syndrome is characterised by periodic fever, aphthous stomatitis, pharyngitis and adenitis. However, there are currently relatively few data on the natural history of this syndrome.

Objective

To describe the presentation, clinical course, doctors'' awareness, therapeutic response and long‐term follow‐up of children with PFAPA syndrome.

Methods

Children with PFAPA syndrome referred over a 5‐year period (from January 1999 to January 2004) were enrolled in the study. Data were gathered from medical records, parents'' interviews, physical examination and telephone calls.

Results

54 patients with PFAPA syndrome were evaluated. Our patients had a higher rate of abdominal pain (65%) and a lower rate of aphthous stomatitis (39%) than those in previous reports. Four different patterns of disease evolution were identified, including the relatively common (n = 14, 26%) and newly described course of alternating remissions and relapses. The remissions lasted 8.5 months on average (range 4–36 months). Diagnosis was established by primary paediatricians in 30 of 54 (56%) patients. However, a substantial delay in diagnosis was apparent (mean 15 months). Episodes were curtailed by a much lower dose of prednisone or equivalent corticosteroid (mean 0.6 mg/kg/day, range 0.15–1.5 mg/kg/day) than reported previously. Tonsillectomy was successful in the prevention of recurrence of further episodes in all six patients who underwent the procedure.

Conclusions

We describe several new characteristics of PFAPA syndrome in children, contributing to our knowledge of this relatively unrecognised but troublesome syndrome. Early diagnosis and appropriate treatment can markedly improve the quality of life of both patients and families.PFAPA (Periodic Fever, Aphthous stomatitis, Pharyngitis and Adenitis) syndrome is characterised by recurrent episodes of fever associated with cervical adenitis, pharyngitis and aphthous stomatitis. The disease belongs to the group of periodic fever syndromes characterised by short episodes of illness that recur regularly for several years, alternating with healthy periods. The syndrome was first described in 1987¹ and the acronym PFAPA was subsequently coined in 1989.² Currently, most of the information gathered about the syndrome is based on only a few reports.^1,2,3,4This study was undertaken to investigate the epidemiological data, clinical course and long‐term follow‐up of children with PFAPA syndrome in central Israel. We were especially interested in aspects that were not described in previous reports, such as doctors'' awareness of the syndrome, adherence to corticosteroid treatment, effective corticosteroid dosage, unique side effects of corticosteroid treatment and a possible correlation between childcare attendance and occurrence of PFAPA syndrome.     

PFAPA syndrome in children evaluated for tonsillectomy.

Among 40 children undergoing tonsillectomy for recurrent pharyngitis, 15 (37.5%) had presented preoperatively with complaints compatible with PFAPA syndrome. All 15 had had periodic fever every three to four weeks and pharyngitis; 12 (80%) had cervical adenitis and five (33%) aphthous stomatitis. All children had been well between episodes and showed a dramatic postoperative improvement. PFAPA syndrome is not uncommon among children having tonsillectomy. Tonsillectomy is curative in most of these patients.     

Noonan syndrome: coagulation and clinical aspects

The study aims were to review the clinical features of a group of patients with Noonan syndrome and to further elucidate their bleeding tendency. Eighteen patients (12M, 6F) aged 2.6–13.3 years underwent a clinical assessment, a questionnaire of their bleeding tendency and laboratory coagulation studies. Nine had cyanotic spells or breathing difficulties after birth; 11 had poor feeding or weight gain. Increased bruising or bleeding was reported in 12 (67%), four of whom had bleeding from the oral cavity. Excessive bleeding was not reported from operative procedures in other sites. Partial thromboplastin time was prolonged in 10 (56%) associated with low levels of clotting factors, particularly XI and XII. Bleeding times were normal; one had marginal thrombocytopenia. Coagulation results did not correlate with bruising history and may not predict bleeding risk. Care is required when Noonan syndrome patients undergo surgery, particularly of the oropharynx, with immediate availability of suitable blood products.     

PFAPA syndrome: a rare cause of periodic fever

PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis, adenopathy) is characterized by abrupt onset of fever, malaise, aphthous stomatitis, tonsillitis, pharyngitis and cervical adenopathy. The age of onset of the disease is four years, with a range of 6 months to 7 years. The syndrome is sporadic and nonhereditary. Long-term sequelae do not develop. A nine- year-old boy presented with sore throat, fever and oral aphthae. After taking a throat culture, he was prescribed oral antipyretic and was called for a follow-up visit the next day. As the culture result was negative, he was given a single dose prednisolone with the suspected diagnosis of PFAPA. Twenty-four hours later his temperature was 36.8 degrees C, with all his complaints regressed. Twenty-two days later the patient was again admitted to our hospital with the same complaints. Again, single dose oral prednisolone was given after a throat culture. On the next day the patient was free of all symptoms and the culture was again normal. To our knowledge this is the first PFAPA case report from Turkey in the literature.     

PFAPA syndrome in children evaluated for tonsillectomy

Among 40 children undergoing tonsillectomy for recurrent pharyngitis, 15 (37.5%) had presented preoperatively with complaints compatible with PFAPA syndrome. All 15 had had periodic fever every three to four weeks and pharyngitis; 12 (80%) had cervical adenitis and five (33%) aphthous stomatitis. All children had been well between episodes and showed a dramatic postoperative improvement. PFAPA syndrome is not uncommon among children having tonsillectomy. Tonsillectomy is curative in most of these patients.     

A clinical review of 105 patients with PFAPA (a periodic fever syndrome)

Aims: We describe the presentations and clinical outcomes of pediatric patients diagnosed with PFAPA (Periodic Fever, Aphthous lesions, Pharyngitis, and cervical Adenitis). Materials and methods: The medical records of children with recurrent fever and referred between 1998 and 2007 to a tertiary pediatric care hospital were reviewed. Children who met clinical criteria for PFAPA were then asked to participate in a follow‐up study. Results: One hundred and five children met study criteria for PFAPA which included at least six episodes of periodic fever. Most (62%) were males, the mean age at onset of PFAPA was 39.6 months (80% were <5 years at onset), the mean duration of individual fever episodes was 4.1 days, and the mean interval between episodes was 29.8 days. Accompanying signs and symptoms included aphthous stomatitis (38%), pharyngitis (85%), cervical adenitis (62%), headache (44%), vomiting with fever spikes (27%) and mild abdominal pain (41%). A prodrome (usually fatigue) preceded the fever in 62% of patients. Parents noted that when their child with PFAPA had fever, other family members remained well. Laboratory tests in patients with PFAPA were nonspecific. Individual episodes of fever usually resolved with a single oral dose (～1 mg/kg) of prednisilone. The interval between fever episodes shortened in 50% of patients who used prednisilone. PFAPA resolved spontaneously (mean length 33.2 months) in 211105 (20%) patients. PFAF’A episodes continued (mean length 23 months) at the end of this study in 661105 (63%) patients. Cimetidine therapy was associated with the resolution of the fevers in 7/26 (27%) patients; tonsillectomy was associated with the resolution of the fevers in 11/11 (100%) patients. Conclusion: PFAPA can usually be defined by its clinical characteristics. Individual febrile episodes usually resolve dramatically with oral prednisilone. The cause of PFAPA is unknown and research is needed to define its etiology. The overall prognosis for children with PFAPA is excellent.     

Costello syndrome: clinical aspects and tumor risk]

Costello syndrome is a sporadic development anomaly suggesting a genetic determinism. Main features include characteristic facial features, mental retardation, growth retardation, cutis laxa, heart malformation, and peri-orificial papillomata. In previous reported cases, the frequency of tumors is 15%, which argues for a screening protocol. The occurrence of a tumor in a child with growth retardation and cutis laxa must be reminiscent of Costello syndrome. The determinism of this syndrome is still unknown, and the hypothesis of an inactivation of a tumor suppressor gene is to be considered.     

Craniofrontonasal syndrome: genetic aspects and description of a clinical case

The authors describe the case of a child with craniofrontonasal syndrome (CFNS) (MIM 304110), the diagnostic process performed, the identification of the main clinical features in the proband (hypertelorism, facial asimmetry, bifid nasal tip, corpus callosum hypoplasia, broad thumb, curly and wiry hair), and the comparison with known data in literature. They also describe the detection, through gene sequencing of EFNB1, of responsible mutation and its correlation with the phenotypic variants. They explain the etiophatogenetic basis of the "unusual" inheritance pattern of CFNS: X-linked disease that occurs with greater severity in heterozygous females than hemizygous males. Finally, attention is placed on the need for careful genetic counseling for patients with CFNS, with special care in familial anamnesis taking. In the studied case, the presence of abnormalities of thumbs in the proband's mother and in two of her cousins, orientates principally toward a mutation of maternal origin or to a suspected somatic and germline mosaicism by creating a recurrence risk greater than general population. Because patients with CFNS reported in the literature are few, the AA consider that the observed case may help to improve understanding of the mechanisms of gene expression responsible for the syndrome, of its peculiar phenotypic manifestations and of its frequency in the population with known and easy to assign phenotypes, and possible mosaicisms that are difficult to detect.     

Epilepsy in Prader-Willi syndrome: clinical,diagnostic and treatment aspects

Background

Epilepsy associated with Prader-Willi syndrome (PWS) represents an early and important complication, often not clearly reported and described in the literature. Consequently, there are controversial data about the clinical characteristics of epilepsy and electroencephalographic (EEG) abnormalities found in these patients.

Data sources

Based on recent original publications, we have reviewed the different types of seizures and EEG findings in PWS patients, the response to antiepileptic treatment, and the prognosis of epilepsy.

Results

The frequency of epilepsy in PWS patients ranges from 4% to 26%. The types of seizure include generalized tonic-clonic seizures, complex partial seizures, atypical absence, staring spells, and myoclonic, tonic and hemiclonic seizures, but the most frequent type is focal epilepsy. Status epilepticus has never been reported. EEG abnormalities are not typical but variable in different patients. However, generalized and focal discharges are the most frequently reported findings. There is no evidence of relationship between the course of epilepsy and frequency, morphology and spread of EEG discharges. However, epilepsy in PWS patients is usually responsive to antiepileptic monotherapy with rapid seizure control and a good outcome.

Conclusions

The frequency of epilepsy is higher in PWS patients than in general populations and this complication can be a challenge for the clinicians of these patients. Prospective studies are needed to confirm the good long-term prognosis.     

Periodic fever, aphthous stomatitis, pharyngitis and adenitis: PFAPA syndrome in Argentina

IntroductionPFAPA syndrome is a benign, non-hereditary condition, of unknown etiology and pathogenesis. There are few reports of it in South America. The purpose of this article is to communicate the experience in a large pediatric hospital in Argentina.Patients and methodsA total of 18 patients were diagnosed with PFAPA between 2002 and 2009 at the Medium Risk Clinic, Prof. Dr. Juan P. Garrahan Pediatrics Hospital, Buenos Aires City. The modified criteria reported by Thomas et al were used for diagnosis. The follow up continued with evaluations during new febrile episodes, clinic check ups and telephone calls.ResultsThe mean age at onset of symptoms was 2.5 years (range: 0.4–7.5) and the mean lag time from onset of symptoms and diagnosis was 3.2 years (range: 0.4-10.9). Fever episodes lasted for a mean of 4.5 days (range: 2-8), with a mean interval of 23 days (range: 15-30) between the beginning of the attacks. Febrile episodes were treated with methyl prednisone at a dose of 1 mg/kg or betamethasone at a dose of 0.15 mg/kg in a single dose. With a mean follow up of 2.6 years (range: 0.5–5.9) 13 patients remain with febrile episodes at a mean interval of 4.6 months (range: 1-12). Five patients did not have febrile crisis for more than a year during the study period and they are considered cured; in this group the disease lasted a mean of 4.7 years (1-9.7).ConclusionsPFAPA syndrome is a sporadic, difficult to diagnose, condition. Both methyl-prednisone and betamethasone have shown to be effective in controlling the symptoms during the febrile crisis. The definitive remission of the syndrome may occur in the first years of onset, although in most patients the febrile episodes continue with an increase of free intervals and attenuated symptoms, and full recovery in prepuberty or adolescence with no sequelae.