Antibiotic prescriptions to children with periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis.

AIM: To investigate the rate of dispensed antibiotic prescriptions to children and adolescents with PFAPA and compare this with the rate for children in the general population. Furthermore, to compare dispensed antibiotic prescription rates before and after a diagnosis of PFAPA was established. METHODS: Patients aged 0-17 years and diagnosed with PFAPA between 1 January 2006 to 31 October 2017 were included retrospectively. Data on dispensed drug prescriptions were obtained from the Swedish National Prescribed Drug Register. RESULTS: The PFAPA cohort received more antibiotic prescriptions than the general population in all but one of the age groups and time periods that were analysed. The largest difference was seen in 2014-2017 in the youngest age group (0-4 years) when children with PFAPA received 1218 antibiotic prescriptions per 1000 person years compared to 345 in the general population (IRR 3.5; 95% CI 2.8-4.4). The yearly number of antibiotic prescriptions to PFAPA patients was reduced from 2.1 before diagnosis to 0.8 after diagnosis, a reduction of 62%. CONCLUSION: This study shows higher rates of dispensed antibiotic prescriptions for children with PFAPA than in the general population. The reduction of prescriptions after an established PFAPA diagnosis indicates that antibiotics were previously incorrectly prescribed for PFAPA episodes.

TNFRSF1A-pR92Q variant identifies a subset of patients more similar to systemic undifferentiated recurrent fever than TNF receptor-associated periodic syndrome.

OBJECTIVES: To describe the clinical phenotype and response to treatment of autoinflammatory disease (AID) patients with the TNFRSF1A-pR92Q variant compared to patients with tumour necrosis factor receptor-associated periodic syndrome (TRAPS) due to pathogenic mutations in the same gene and patients diagnosed with other recurrent fever syndromes including periodic fever with aphthous stomatitis, pharyngitis, and adenitis (PFAPA) and syndrome of undefined recurrent fever (SURF). METHODS: Clinical data from pR92Q variant associated AID, classical TRAPS, PFAPA and SURF patients were obtained from the Eurofever registry, an international, multicentre registry enabling retrospective collection of data on AID patients. RESULTS: In this study, 361 patients were enrolled, including 77 pR92Q variant, 72 classical TRAPS, 152 PFAPA and 60 SURF patients. pR92Q carriers had an older age of disease onset than classical TRAPS and PFAPA patients. Compared to pR92Q variant patients, classical TRAPS patients had more relatives affected and were more likely to have migratory rash and AA-amyloidosis. Despite several differences in disease characteristics and symptoms between pR92Q variant and PFAPA patients, part of the pR92Q variant patients experienced PFAPA-like symptoms. pR92Q variant and SURF patients showed a comparable clinical phenotype. No major differences were observed in response to treatment between the four patient groups. Steroids were most often prescribed and effective in the majority of patients. CONCLUSIONS: Patients with AID carrying the TNFRSF1A-pR92Q variant behave more like SURF patients and differ from patients diagnosed with classical TRAPS and PFAPA in clinical phenotype. Hence, they should no longer be diagnosed as having TRAPS and management should differ accordingly.

Gray zone in the spectrum of autoinflammatory diseases: familial Mediterranean fever accompanying periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome: single-center experience.

Despite the advanced knowledge concerning autoinflammatory diseases (AID), more data regarding the optimal treatment options and outcomes of the children who met the criteria of more than one AID are required. This study aimed to describe the demographic and clinical characteristics of children from familial Mediterranean fever (FMF)-endemic countries who meet both the FMF and the periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome criteria. Moreover, we aimed to measure the response rates to colchicine and tonsillectomy and evaluate the factors affecting the colchicine response in these patients. The study was conducted at pediatric rheumatology tertiary centre. A total of 131 patients (58 females; 73 males) who met both the modified Marshall and pediatric FMF criteria were included. The median age at onset was 18 months (1-77 months), and the mean age at diagnosis was 47 ± 21.88 months. The median interval between episodes was 21 (7-90) days. The median disease duration was 46 (6-128) months. Consanguineous marriage was detected in 17 (13%) of the patients. The most common clinical finding was fever (100%), followed by exudative pharyngitis (88.5%), abdominal pain (86.3%), arthralgia (61.8%), stomatitis (51.1%), adenitis (42%), myalgia (28.7%), chest pain (16%), maculopapular rash (12.2%), arthritis (8.4%), and erysipelas-like rash (4.6%). MEFV gene variants were identified in 106 (80.9%) patients. The most common variants were M694V heterozygous (29%). We found that patients with tonsillopharyngitis, aphthous stomatitis, and PFAPA family history were more likely to be colchicine-resistant and tonsillectomy responsive, while those with exon 10 MEFV gene mutations were more prone to have a favorable response to colchicine.     Conclusion: PFAPA syndrome patients with exon 10 MEFV gene mutation, showing typical FMF symptoms, should be treated with colchicine, even after tonsillectomy. In multivariate analysis, PFAPA family history and lack of exon 10 MEFV gene mutations were independent risk factors for colchicine resistance. Thus, tonsillectomy may be recommended as a possible treatment option for these patients. It has yet to be clarified when colchicine treatment will be discontinued in patients whose attacks ceased after tonsillectomy that was performed due to colchicine unresponsiveness. What is Known: • A certain number of patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome concomitantly fulfill the familial Mediterranean fever (FMF) criteria. • While colchicine is proposed as a first treatment choice in familial Mediterranean fever (FMF), corticosteroids are recommended as a first-line treatment in PFAPA syndrome patients. What is New: • In patients with concomitant PFAPA syndrome and FMF, PFAPA family history and lack of exon 10 MEFV gene mutation are predictive factors of colchicine resistance. • The presence of exon 10 MEFV gene mutations in patients with concomitant FMF and PFAPA syndrome has a favourable effect on response to colchicine treatment.

Evaluation of the Levels of Blood Cells, Vitamin D, and Inflammatory Factors in Children with PFAPA Syndrome.

BACKGROUND: The syndrome of periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA syndrome) is the most common type of recurrent fever in childhood. The aim of this study was evaluation of the levels of blood cells, vitamin D, and inflammatory factors in children with PFAPA syndrome. METHODS: This retrospective descriptive study was conducted on the recorded information of children with PFAPA syndrome referred to the children's specialty clinic of Imam Khomeini Hospital in Ilam city from March 2021 to February 2022. Complete demographic information, presence of underlying disease, changes in blood cells, vitamin D level and inflammatory factors were obtained from the patients' records. Diagnosis of PFAPA syndrome was performed according to Thomas' criteria. RESULTS: This study was conducted on 40 children with PFAPA syndrome. The majority of patients were male and in the age range of 3 - 4 years. The results show that the average percentage of neutrophil and lymphocyte cells in the blood of patients was 54.45% and 40.62%, respectively. Also, 6 (15%), 3 (7.5%), and 31 (77.5%) patients had normal neutrophil levels, neutropenia, and neutrophilia, respectively. Regarding lymphocyte cells, 26 (65%), 8 (20%), and 6 (15%) people had normal lymphocyte level, lymphocytosis and lymphopenia, respectively. ESR levels increased in all patients (average percentage: 16.72). CRP level was negative in 9 (22.5%) and +1 in 19 (47.5%) patients, respectively. The results showed that 33 (82.5%) patients were deficient in vitamin D level. CONCLUSIONS: The etiology and pathogenesis of PFAPA is still unknown; however, the rapid response to corticosteroid therapy is the indication of an immune deregulation. Treatment guidelines for PFAPA syndrome based on controlled studies are needed, as well as a better understanding of the disease itself.

Long-term efficacy of tonsillectomy/adenotonsillectomy in patients with periodic fever aphthous stomatitis pharyngitis adenitis syndrome with special emphasis on co-existence of familial Mediterranean fever.

Periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome is one of the most common autoinflammatory fever disorders in the childhood which may co-exists with familial Mediterranean fever (FMF) causing treatment complexity. As the role of surgery in PFAPA syndrome is still controversial, in this paper, our aim is to present our results of tonsillectomy/adenotonsillectomy in the treatment of PFAPA syndrome. Archives of a tertiary care hospital were investigated for patients who underwent tonsillectomy or adenotonsillectomy due to PFAPA Syndrome between 2010 and 2020. 344 patients were found but only 281 of them were accessible. Through phone call interview and chart review methods, preoperative and postoperative the number and severity of the attacks and general satisfaction after the operation were recorded and analyzed. Also, patients with concomitant FMF were analyzed separately. A total of 281 patients were included in the study. There was no improvement in 10 (3.55%) patients. Eight (2.84%) patients showed mild improvement, 29 (10.32%) patients had moderate improvement and 234 (83.27%) patients had full recovery after tonsillectomy. There were 266 PFAPA patients without FMF. No improvement, mild improvement, moderate improvement, and full recovery in this patient group were 5 (1.9%), 6 (2.3%), 25 (9.4%) and 230 (86.5%), respectively. FMF was present in 5.33% (15/281) of the patients. In PFAPA + FMF group 5 patients had no improvement (33.3%), 2 had mild improvement (13.3%), 4 had moderate improvement (26.7%) and 4 had full recovery (26.7%). Benefit of tonsillectomy was significantly lower in the patients with concomitant FMF when compared to the patients who did not have FMF (p < 0.001). Age of diagnosis, age of operation, severity of the disease, type of operation, and gender were found to have no significant relationship with the benefit from surgery (p < 0.05). According to the findings of this study, tonsillectomy is an effective long-term treatment for PFAPA syndrome with success rate of 83.27%. Also, preoperatively FMF should be considered in these patients, which dramatically reduces surgical efficacy.

Diagnostic performance of routine blood parameters in periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome.

BACKGROUND: We aimed to investigate the difference between PFAPA and streptococcal tonsillitis (Strep Pharyngitis) by using blood parameters. We want to evaluate the relationship between periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome, and tonsillitis by using NLR. METHODS: The data of 141 pediatric patients who had applied to our clinic between October 2016 and March 2019 and were diagnosed with PFAPA syndrome and tonsillitis were reviewed from hospital records. The demographic data of the study group were recorded, as were their WBC, neutrophil, and lymphocyte counts, NLR, and MPV values, which are obtained by proportioning these two counts. RESULTS: CRP and ESR values were significantly higher in the PFAPA group (p = 0.026 and p < 0.001, respectively). No significant difference was determined between the groups in terms of platelet count or lymphocyte count. Receiver operating curve analyses were calculated. The AUC was 0.713 ± 0.04 according to age, and the CRP was 0.607 ± 0.04 (95% confidence interval). Using a cutoff point of >49 months for age, the sensitivity was 0.71 and the specificity was 0.67. CONCLUSION: With simple laboratory parameters, PFAPA syndrome can be differentiated from a diagnosis of tonsillitis. This may reduce the costs associated with unnecessary antibiotic use. However, these findings still need to be confirmed by other future studies.

PFAPA syndrome in children.

ABSTRACT: Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is, as the name implies, characterized by an extremely regular cycle of fevers that is accompanied by one or more other symptoms such as oral ulcers, pharyngitis, adenitis, tonsillitis, sore throat, cervical adenopathy, and headache. Originally known as Marshall syndrome, PFAPA is most commonly identified in children younger than age 5 years; however, adults may also present with the disease, though they may report additional symptoms. PFAPA is now understood to be a diagnosis of exclusion. Laboratory studies are typically unremarkable except for increases in acute phase reactants such as C-reactive protein. Treatment is primarily supportive and most frequently uses systemic steroids to suppress the inflammatory response. Acute flares are self-limited, and the syndrome typically resolves on its own as the child reaches age 7 or 8 years.

The rs13075270 and rs13092160 polymorphisms of CCR1 and CCR3 genes on oral aphthous-like lesions in PFAPA syndrome.

Fever is a common symptom of infection in children. Periodic fever syndromes are less common but more complex. One of these Periodic fever syndromes is PFAPA (periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis) syndrome which is known as the most benign syndromes. The cause of this disease is unknown. Various factors, including environmental and genetic factors, are involved in the development of this disease. In this study, the association of rs13075270 and rs13092160 polymorphisms were investigated in CCR1 and CCR3 genes with susceptibility to this syndrome in the Chinese population. In this regard, 38 patients with PFAPA syndrome and 100 healthy individuals were selected. After DNA sampling and extraction, polymorphisms of CCR1 and CCR3 receptor genes were examined by the PCR-RFLP method. Findings were analyzed using SPSS software version 22 with a significant level of P <0.05. The frequency of T/T genotype rs13092160 polymorphism in the patient and control groups was 78.95% and 83%, respectively, C/T genotype was 21.05% and 17% (P = 0.421). The frequency of the C/C genotype was 0 in both groups. Regarding rs13075270 polymorphism, the frequency of T/T genotype in patient and control groups was 15.79% and 81%, C/T genotype was 78.95% and 18% and C/C genotype was 5.26% and 1%, respectively (P<0.05). Thus, in rs13075270 polymorphism, the C/T genotype was associated with the risk of PFAPA syndrome (P<0.05), but rs13092160 polymorphism did not show a significant difference between individuals with PFAPA syndrome and controls.

Recurrent aphthous stomatitis: A comprehensive review and recommendations on therapeutic options.

Recurrent aphthous stomatitis (RAS) is a common chronic disease in the oral mucosa that affects about 20% of the population. It is characterized by solitary or multiple, recurrent, small ulcers with erythematous haloes and yellow/gray floors. RAS can be managed through a wide variety of preventative measures and therapies, intending to reduce ulcer pain, stimulate ulcer healing, and/or prevent ulcer recurrence. First-line treatment options include topical medications in the form of corticosteroids (triamcinolone acetonide), anti-inflammatory drugs (amlexanox), antibiotics (doxycycline), and antiseptics (lidocaine). In more severe cases of RAS where local treatment is insufficient, systemic drugs in the form of corticosteroids (prednisone), immunomodulatory drugs (thalidomide), and antibiotics/antimicrobials (clofazimine) can prove effective. This review will summarize current treatment options for RAS with discussion of prevention, topical measures, natural treatments, systemic therapies, and new potential therapies. Furthermore, this review will provide recommendations on therapeutic options for RAS based on disease severity and patient circumstances.

Galectin-3: a new biomarker for differentiating periodic fever, adenitis, pharyngitis, aphthous stomatitis (PFAPA) syndrome from familial Mediterranean fever?

Differentiating PFAPA (periodic fever, aphthosis, pharyngitis, and adenitis) syndrome from familial Mediterranean fever (FMF) could be challenging in some cases. Galectin-3 is a lectin with regulatory functions in apoptosis and inflammation. We aimed to test whether galectin-3 could be a biomarker for differentiating PFAPA syndrome from FMF. Patients with PFAPA syndrome, FMF, cryopyrin-associated periodic syndrome (CAPS), and streptococcal pharyngitis, and healthy controls were included in this study. Serum galectin-3 levels were measured using enzyme-linked immunosorbent assay. Eighty-seven patients (36 with PFAPA, 39 with FMF, 8 with CAPS, 4 with streptococcal pharyngitis), and 17 healthy controls were included. Blood samples were drawn during attacks from 20 PFAPA and 7 FMF patients and attack-free periods from 22 PFAPA, 35 FMF, and 8 CAPS patients. The median serum galectin-3 level in the PFAPA-attack group (1.025 ng/ml) was significantly lower than the levels in healthy control (2.367 ng/ml), streptococcal pharyngitis (3.021 ng/ml), FMF attack (2.402 ng/ml), and FMF-attack-free groups (2.797 ng/ml) (p = 0.006, 0.03, 0.01, and < 0.001, respectively). PFAPA-attack-free group had lower galectin-3 levels than the FMF-attack-free group (1.794 vs. 2.797 ng/ml, respectively; p = 0.01). Galectin-3 levels did not differ significantly between CAPS and attack-free PFAPA patients (1.439 ng/ml vs. 1.794 ng/ml, respectively; p = 0.63). In our study, for the first time, we defined galectin-3 as a promising biomarker that differs between PFAPA and FMF patients during both disease flares and attack-free periods. Further studies with high number of patients could validate its role as a biomarker.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome (PFAPA) or recurrent urinary tract infections: a case report.

BACKGROUND: Fever is the most frequent reason for medical consultation in children, and makes up 15-25% of all consultations in primary care and emergency departments. In here we report a case of a 13 year-old girl who referred with an unusual presentation of fever and was misdiagnosed with recurrent urinary tract infection for 8 years. CASE PRESENTATION: This is a Clinical Reasoning Cycle case study. A 13 year-old girl was referred with a chief complaint of recurrent fevers from 8 years. During her first febrile episode, she had a 5-day high-grade fever associated with loss of appetite. Her physical examination at that time was unremarkable. Blood tests showed leukocytosis with a shift to the left and urine examination was in favor of pyuria. The urine culture was positive for bacterial growth. The episodes of fever were repeated every 45 days. Accordingly, the patient was diagnosed as a case of recurrent urinary tract infection. In the intervals between her febrile episodes, the patient was healthy and laboratory tests were normal. Ultrasonography, voiding cystourethrogram and dimercaptosuccinic acid scans were normal. During her last visit, the patient mentioned difficulty in swallowing and on examination cervical lymph nodes, exudative tonsillitis and painful aphthous stomatitis were detected. All antibiotics were stopped and corticosteroids were started. The patient's symptoms were relieved and the interval between her febrile episodes became longer. CONCLUSIONS: Our study shows that a patient should never be marked, particularly when the symptom and signs aren't completely justifying a patient's condition.

Making a diagnosis of periodic fever syndrome: Experience from a single tertiary centre.

AIM: This study aims to evaluate the utility of genetic testing of patients diagnosed with periodic fever syndromes and to assess the validity of existing scoring criteria. METHODS: This study retrospectively reviewed the clinical history of patients diagnosed with periodic fever syndromes at Queensland Children's Hospital between November 2014 and June 2018. RESULTS: Forty-three patients were diagnosed with periodic fever syndromes. Diagnoses in the cohort included periodic fever, adenitis, pharyngitis and aphthous stomatitis (10), tumour necrosis factor receptor-associated periodic syndrome (9), cryopyrin-associated periodic syndrome (6), mevalonate kinase deficiency (4) while 14 remained unspecified. No presenting symptoms were uniquely associated with any particular diagnosis. Genetic testing of between 1 and 26 genes was performed in 26 (60%) patients. Two (7.7%) patients had pathogenic variants identified. Variants of uncertain significance which were insufficient to confirm a monogenic disorder were identified in a further 7 (27%) patients. The Eurofever classification criteria correlated with clinical diagnosis for patients diagnosed with cryopyrin-associated periodic syndrome (P = 0.046) and tumour necrosis factor receptor-associated periodic syndrome (P = 0.025) but not for patients diagnosed with mevalonate kinase deficiency (P = 0.47); however, the Eurofever classification criteria were often positive for more than one diagnosis in these patients. CONCLUSION: The European classification criteria can form a potentially useful tool to guide diagnosis; however, clinical judgement remains essential, because the score is often positive for multiple diagnoses. The diagnostic yield of genetic testing in this cohort was low and genetic testing may be more useful to confirm a strong clinical suspicion than to clarify a diagnosis for patients with less clear symptoms.

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome: Clinical characteristics and treatment outcomes - a single center study in Japan.

BACKGROUND: Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is an autoinflammatory disease occurring in children. Although PFAPA is the most common periodic fever syndrome found in children, there are only a few studies defining the clinical characteristics and the efficacy of treatment strategies among Japanese children. This study aimed to clarify the demographic characteristics and clinical features of patients with PFAPA syndrome and to evaluate treatment efficacy. METHODS: We retrospectively reviewed the clinical features of children with PFAPA who visited Saitama Children's Medical Center between January and December 2019. We also evaluated treatment strategies and their efficacy; abortive treatment with corticosteroids, prophylaxis with cimetidine or colchicine, and surgical management with tonsillectomy. RESULTS: A total of 100 Japanese children (61% male) with PFAPA were included. Median age of onset was 3 years, median duration of fever episodes was 5 days, and median interval between episodes was 4 weeks. The symptoms (frequencies) were pharyngitis (89%), exudate on tonsils (71%), cervical adenitis (50%), and aphthous stomatitis (49%). Approximately 37% of patients took prednisolone for aborting fever attacks, showing a 100% response; 93% were treated with cimetidine, showing an 79.6% response, and 18% were treated with colchicine, showing a 66.7% response. Only one patient underwent tonsillectomy. CONCLUSIONS: Among Japanese children with PFAPA, 28% of them were ≥5 years with a male predominance. Pharyngitis is the most frequent symptom associated with fever. Cimetidine is suitable for initial therapy because of its safety and efficacy.

[Experience of using bacteriophages in the complex treatment of children with aphthous stomatitis]. / Opyt ispol'zovaniya bakteriofagov v kompleksnom lechenii detei s aftoznym stomatitom.

Aphthous stomatitis (AS) is one of the most common diseases of the oral mucosa in children. A significant role in the pathogenesis of AS is assigned to the infectious-allergic factor. THE AIM: Of the work was to evaluate the clinical effectiveness of topical application of bacteriophages in the complex treatment of children with aphthous stomatitis. MATERIALS AND METHODS: The main group included 30 children with AS aged 4 to 15 years. The control group consisted of 20 healthy children without AS and without concomitant somatic pathology at the age of 4 to 15 years. The effectiveness of the therapy was evaluated based on the results of repeated bacteriological examination of the oral microflora, conducted 1 month after phage treatment, as well as the dynamics of clinical manifestations: reduction in size or complete epithelization of defects. RESULTS: The use of bacteriophage in the complex treatment of children with AS was accompanied by positive dynamics of clinical and laboratory parameters in all patients: a significant decrease in microbial contamination and the number of individual pathogenic microflora species against the background of normalization of local microbiocenosis in the oral cavity. CONCLUSION: The obtained clinical and laboratory data allowed improving the scheme of complex treatment of AS in children by the use of bacteriophages.

Undifferentiated recurrent fevers in pediatrics are clinically distinct from PFAPA syndrome but retain an IL-1 signature.

Autoinflammatory disorders of the innate immune system present with recurrent episodes of inflammation often beginning in early childhood. While there are now more than 30 genetically-defined hereditary fever disorders, many patients lack a clear diagnosis. Many pediatric patients are often grouped with patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome despite failing to meet diagnostic criteria. Here, we categorize these patients as syndrome of undifferentiated recurrent fever (SURF), and identify the unique features which distinguish them from the PFAPA syndrome. SURF patients were more likely to report gastrointestinal symptoms of nausea, vomiting and abdominal pain, and experienced inconsistent responses to on-demand steroid therapy compared to PFAPA patients. For this previously undefined cohort, an optimal course of therapy remains uncertain, with medical and surgical therapies largely driven by parental preference. A subset of patients with SURF underwent tonsillectomy with complete resolution. Flow cytometric evaluation demonstrates leukocytic populations distinct from PFAPA patients, with reduced CD3+ T cell numbers. SURF patient tonsils were predominantly characterized by an IL-1 signature compared to PFAPA, even during the afebrile period. Peripheral blood signatures were similar between groups suggesting that PFAPA and SURF patient tonsils have localized, persistent inflammation, without clinical symptoms. These data suggest that SURF is a heterogenous syndrome on the autoinflammatory disease spectrum.

A Case of Cyclic Neutropenia and Associated Amyloidosis.

Cyclic neutropenia has been rarely associated with chronic inflammation and development of reactive AA amyloidosis. We report a family with cyclic neutropenia with associated renal and thyroid amyloid. A 12-year-old female presented with thyromegaly, recurrent aphthous ulcers, severe neutropenia, and renal failure. Renal and thyroid biopsies revealed abundant amyloid deposition. Presence of a heterozygous ELANE c.358 A>T gene mutation p.I120F variant with autosomal dominant inheritance confirmed the diagnosis of cyclic neutropenia. The patient's father also had neutropenia and amyloidosis with renal failure. We started filgrastim to attenuate neutropenia and thereby reduce chronic inflammation and minimize further amyloid deposition.

Clinical Usefulness of Acute-Phase Markers in Distinguishing between PFAPA and Other Exudative Tonsillitis Causes: A Methodological Study.

BACKGROUND: We investigated the practical use of procalcitonin (PCT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and complete blood count (CBC) parameters in distinguishing periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome (PFAPA) attacks from exudative tonsillitis associated with group A streptococcus (GAS) and Epstein-Barre virus (EBV). METHODS: The study population consisted of cases with exudative tonsillitis who had been subsequently diagnosed as PFAPA, EBV, and GAS tonsillitis through a period of 6 years. We retrieved the CBC, ESR, CRP and PCT data from patients' medical records. RESULTS: Of the patients, 47 (35.6%) had PFAPA, 36 (27.3%) had GAS and 49 (37.1%) had EBV tonsillitis. Median CRP, ESR and PCT values of patients with PFAPA were 78 (17-92) mg/dl, 44 (11-83) mm/h, 0.16 (0.01-1.45) ng/ml, respectively. The CRP and ESR levels were significantly higher in PFAPA and GAS groups compared with the EBV group (p = 0.001). There was no significant difference between the groups regarding the PCT levels. CONCLUSION: The study indicated no benefit of PCT in distinguishing PFAPA from the others. However, we found that CRP, ESR, and CBC parameters could be useful in identifying PFAPA and GAS than EBV tonsillitis.

Lingual Tonsillectomy: Successful Treatment of Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Cervical Adenitis Syndrome.

BACKGROUND: PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis) syndrome is diagnosed clinically. Adult-onset PFAPA syndrome is rare and often has a more diverse clinical presentation that its childhood counterpart. This is the first reported case of adult-onset PFAPA syndrome with complete response to lingual tonsillectomy. CASE SUMMARY: A 41-year-old man was evaluated for periodic fevers associated with uvulitis, cervical lymphadenitis, pharyngitis, and lower extremity rash. He had a variable response to steroids and was intolerant of colchicine. Laboratory workup revealed intermittent elevation of erythrocyte sedimentation rate and C-reactive protein level. Computed tomography neck and laryngoscopy confirmed adenoidal and lingual tonsillar hypertrophy. He underwent adenoidectomy and lingual tonsillectomy with resolution of symptoms. CONCLUSIONS: Hypertrophy of the remaining lymphoid structures within Waldeyer's ring may be associated with remote recurrence of PFAPA syndrome after tonsillectomy. Lingual tonsillectomy may be an alternative treatment strategy in select patients with PFAPA, prominent lingual hypertrophy, and incomplete response to steroids.

[Clinical features of children with periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome: an analysis of 13 cases].

OBJECTIVE: To study the clinical features of children with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome, a polygenic and multifactorial autoinflammatory disease with unknown pathogenesis. METHODS: A retrospective analysis was performed on the medical data of 13 children with PFAPA syndrome. RESULTS: All 13 children had disease onset within the age of 3 years, with a mean age of onset of (14±10) months. They all had periodic fever, with 8-18 attacks each year. The mean interictal period of fever was (30±5) days. Pharyngitis, cervical adenitis, and aphthous stomatitis were the three cardinal symptoms, with incidence rates of 100% (13/13), 85% (11/13), and 38% (5/13) respectively. There were increases in white blood cells, C-reactive protein, and erythrocyte sedimentation rate during fever. Of all the 13 children, 6 underwent whole exome sequencing and 7 underwent panel gene detection for autoinflammatory disease, and the results showed single heterozygous mutations in the MEFV gene in 6 children (46%). Recurrent fever in all children gradually returned to normal without antibiotics. Ten children were treated with a single dose of glucocorticoids, and fever was relieved after treatment. Of all the children, 4 were treated with cimetidine, among whom 2 had response; 4 children were treated with colchicine, among whom 2 had response and 2 were withdrawn from the drug due to adverse reactions. Tonsillectomy was performed for 2 children, among whom 1 was followed up for 3 years without recurrence and 1 still had recurrence. CONCLUSIONS: For children with unexplained periodic fever with early onset accompanied by pharyngitis, cervical adenitis, aphthous stomatitis, elevated inflammatory indices, and good response to glucocorticoids, PFAPA syndrome should be considered. This disorder has good prognosis, and early diagnosis can avoid the long-term repeated use of antibiotics.

Mosaic Small Supernumerary Marker Chromosome Derived from Five Discontinuous Regions of Chromosome 8 in a Patient with Neutropenia and Oral Aphthous Ulcer.

Small supernumerary marker chromosomes (sSMCs) are characterized as additional centric chromosome fragments which are too small to be classified by cytogenetic banding alone and smaller than or equal to the size of chromosome 20 of the same metaphase spread. Here, we report a patient who presented with slight neutropenia and oral aphthous ulcers. A mosaic de novo sSMC, which originated from 5 discontinuous regions of chromosome 8, was detected in the patient. Formation of the sSMC(8) can probably be explained by a multi-step process beginning with maternal meiotic nondisjunction, followed by post-zygotic anaphase lag, and resulting in chromothripsis. Chromothripsis is a chromosomal rearrangement which occurs by breakage of one or more chromosomes leading to a fusion of surviving chromosome pieces. This case is a good example for emphasizing the importance of conventional karyotyping from PHA-induced peripheral blood lymphocytes and examining tissues other than bone marrow in patients with inconsistent genotype and phenotype.