PANDAS: pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections--an uncommon,but important indication for tonsillectomy

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections, also know as "PANDAS," is well described in the neurologic and psychiatric literature. PANDAS is associated with obsessive compulsive disorders (OCD) and tic disorders. The streptococcal infections may trigger an autoimmune reaction that exacerbates these conditions. Recurrent streptococcal tonsillitis is one of the recurrent infections associated with PANDAS. This paper reviews the case reports of two brothers, one with OCD and the other with a tic disorder, both of whom improved significantly after undergoing adenotonsillectomy for treatment of their recurrent tonsillitis. A review of the pathophysiology and current understanding of PANDAS is presented.     

Pediatric autoimmune neuropsychiatric disorders and streptococcal infections: role of otolaryngologist

OBJECTIVE: To increase awareness and understanding of the putative role of streptococcal infection in the development of neuropsychiatric disorders in children and to discuss therapeutic options in this group of patients. METHODS: Case illustration and literature review. RESULTS: Two siblings, one with obsessive-compulsive disorder (OCD) and one with a tic disorder, had tonsillectomy for recurrent streptococcal pharyngitis. At the latest follow-up visit (11 mo postoperatively), both patients exhibited significant improvement in their psychiatric illnesses. We discuss these cases as well as the diagnosis, pathophysiology, and treatment of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). CONCLUSION: PANDAS is an active area of research investigating the relationship between streptococcal infections and the development of obsessive-compulsive disorder or tic disorders (or both) in children. The etiopathogenesis of PANDAS is thought to reflect autoimmune mechanisms and involvement of the basal ganglia of susceptible hosts. Because otolaryngologists evaluate a large portion of pediatric patients with recurrent streptococcal pharyngitis, it is important to be aware of this association and to manage these patients appropriately.     

Spasmodic dysphonia in an adolescent patient with an autoimmune neurologic disorder

Pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) has been primarily described in the neurology and psychiatry literature. The symptoms of this syndrome typically are a range of obsessive compulsive disorders and neuromuscular tics. The otolaryngologist occasionally becomes involved with these children when it is deemed that chronic tonsil infections are the source. We report here on a child diagnosed with PANDAS who presented with severe ventricular hyperfunction and adductor spasmodic dysphonia. She was treated with botulinum toxin, which resulted in a significant improvement in subjective voice as well as reduced jitter and shimmer on objective voice measurements.     

Síndrome PANDAS: ¿una nueva indicación de amigdalectomía?

PANDAS Syndrome (Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus) is a rare disease described in 1998. In this disease, there is a relationship between group A beta haemolytic streptococcal tonsil infections and the exacerbation of neuropsychiatric disorders. A case report of a 9-year-old child with PANDAS syndrome is presented. This child has had no further symptoms after tonsillectomy. The understanding about PANDAS syndrome and tonsillectomy is reviewed.     

Efficacy of tonsillectomy in treatment of recurrent group A beta-hemolytic streptococcal pharyngitis

OBJECTIVE: The objective of this study was to determine whether children with tonsillectomies experienced fewer recurrent group A beta-hemolytic streptococcal (GABHS) infections after surgery compared with children who did not receive tonsillectomies. STUDY DESIGN/METHODS: The authors conducted a retrospective cohort study of 290 children 4 to <16 years who experienced three or more episodes of group A beta-hemolytic streptococcal pharyngitis at least 1 month apart in 12 months. RESULTS: Children without tonsillectomy were 3.1 times (95% confidence interval, 1.9-4.9; P < .001) more likely to develop a subsequent group A beta-hemolytic streptococcal pharyngitis infection during follow up than children who underwent tonsillectomy after adjusting for the number of group A beta-hemolytic streptococcal pharyngitis infections per patient within the previous year and the presence of preexisting conditions. Among the children who developed a subsequent group A beta-hemolytic streptococcal pharyngitis infection, the children without a tonsillectomy developed a group A beta-hemolytic streptococcal pharyngeal infection sooner (median, 0.6 vs. 1.1 years). CONCLUSIONS: Tonsillectomy is associated with a decrease in the number of group A beta-hemolytic streptococcal pharyngitis infections in children with a history of recurrent groups A beta-hemolytic streptococcal pharyngitis infection. Tonsillectomy also increased the amount of time before development of further GABHS pharyngitis.     

Decreased serum and pharyngeal antibody levels specific to streptococcal lipoteichoic acid in children with recurrent tonsillitis

OBJECTIVE: Streptococcus (S.) pyogenes is a common cause of primary as well as recurrent tonsillitis (RT). Lipoteichoic acid (LTA) has been proposed as a possible candidate for vaccine formulation against streptococcal infections, because LTA is a common constituent of streptococci and the antibody to LTA inhibits bacterial attachment to epithelial cells in vitro. Streptolysin-O and streptococcal whole cell body are highly immunogenic and the antibodies to these antigens are reported to be better parameters for streptococcal infections The objective of the present study is to investigate how systemic and local immune activities against S. pyogenes may be associated with RT. METHODS: Sera from 178 children with or without RT aged 1-15 years with a median age of 5 years were investigated for the levels of total immunoglobulins and antibodies specific to streptococcal antigens such as whole cell body, LTA, and streptolysin-O. Pharyngeal secretions from 67 children with or without RT aged 2-14 years with a median age of 6 years were subjects to secretory IgA (SIgA) antibody levels to streptococcal LTA. The antibodies to whole cell body and LTA were measured by enzyme-linked immunosorbent assay. Total immunoglobins and the anti-streptolysin-O antibody were assayed by nephelometry. RESULTS: An age-matched comparison revealed that either levels of serum IgG antibody or pharyngeal SIgA antibody to streptococcal LTA at 2-5 years of age were significantly lower in RT children than in non-RT children (1.39 vs. 5.14 microg/ml, P=0.001; 10.6 vs. 29.9 units/ng/ml total SIgA, P=0.015; respectively) and correlated inversely to episodes of tonsillitis (r=-0.242, P=0.024; r=-0.3, P=0.024; respectively). Either serum total immunoglobulin levels of IgG or IgA correlated positively to episodes of tonsillitis in children aged 2-5 years (r=0.293, P=0.011; r=0.361, P=0.002; respectively). No difference was found on either serum levels of IgG antibody to streptococcal whole cell body or antibody to streptolysin-O between RT and non-RT children in any age-matched comparisons. High serum antibody levels to whole cell body was associated with high antibody levels to streptococcal LTA in non-RT children (r=0.198, P<0.05), but no association was found between these antibody levels in RT children. CONCLUSIONS: Selective immunologic failure in systemic and pharyngeal antibody response to streptococcal LTA may be a potential cause of RT in young children.     

Association of allergy, asthma and IgE sensitisation to adenoidectomy and infections in children

OBJECTIVE: To find out whether previous adenoidectomy is associated with asthma, allergic symptoms or allergen-specific IgE antibodies. RECRUITMENT AND METHODS: We recruited 213 paediatric patients admitted for elective tonsillectomy and 155 paediatric controls. Using a structured questionnaire, we recorded their respiratory symptoms, allergies, bronchial asthma and environmental factors. Serum IgE antibodies against respiratory allergens were screened. Patients were divided into those previously adenoidectomised (n = 100) or not adenoidectomised (n = 113). RESULTS: Any allergy (p = 0.007) and non-antibiotic allergy diagnosed by a doctor (p = 0.015), and asthma (p = 0.015) were more common among adenoidectomised than non-adenoidectomised children under the age of seven. Between ages 7 and 11, neither any kind of allergy nor asthma were associated with earlier adenoidectomy. In the oldest age group (12 to 17), only antibiotic allergy was more common in adenoidectomised children. Recurrent otitis media (p < 0.001) and recurrent sinusitis (p = 0.007) were more common in adenoidectomised children. After controlling for recurrent respiratory infections, doctor-diagnosed allergy remained significantly associated with adenoidectomy in the youngest age group. Prevalence of specific IgE did not differ between the patient groups, or between school-aged patients and controls. CONCLUSIONS: Our results suggest that hypersensitivity disorders and infections may share aetiological factors. However, as adenoidectomised children of any age did not have higher levels of specific IgE, it seems possible that allergy is either clinically over-diagnosed or insufficiently detected by serology among young adenoidectomised children.     

Periodic fever and pharyngitis in young children: a new disease for the otolaryngologist?

OBJECTIVE: A clinical entity consisting of periodic fever associated with aphthous stomatitis, pharyngitis and cervical adenitis termed "PFAPA syndrome" in young children (<5 years old) may be unfamiliar to otolaryngologists. We present our 5-year experience of PFAPA syndrome. DESIGN: Case series. SETTING: Tertiary academic. PATIENTS: A 5-year retrospective chart review for children (<5 years old) who have undergone tonsillectomies with and without adenoidectomies was conducted. Medical records from subjects who underwent the procedures for recurrent pharyngitis were reviewed with reference to a history of periodic fever and stomatitis associated with pharyngitis. INTERVENTIONS: Tonsillectomy with and without adenoidectomy. MAIN OUTCOME MEASURE: The objective measure was a comparison of the number of visits to the primary care physician for pharyngitis associated with fever in a 3-month period before and after the surgical intervention. The subjective measure was a telephone interview evaluating preoperative and postoperative symptoms. RESULTS: Of the 117 patients identified, 22 (19%) underwent surgery for recurrent pharyngitis. Five subjects (average age, 2.5 years) were identified as having PFAPA syndrome. The average number of preoperative PFAPA-related complaints was 11.6 compared with 0.2 for the number of postoperative PFAPA-related complaints (P=.03). CONCLUSIONS: Our experience suggests that PFAPA syndrome is an uncommon disease. Most of these children have undergone workup(s) for sepsis performed by their pediatricians because of the associated high fever. The clinical history of this cohort was quite distinctive. This small sample suggests a significant decrease if not cessation of pharyngitis following surgical intervention.     

A role for tonsillectomy in the treatment of psoriasis?

Our objective was to determine whether tonsillectomy is beneficial in the treatment of recurrent childhood guttate psoriasis that is associated with recurrent streptococcal pharyngitis and tonsillitis. We retrospectively reviewed the cases of two children who were referred to our facility for treatment of repeated exacerbations of psoriasis and recurrent streptococcal pharyngotonsillitis. Both patients experienced a significant improvement in their psoriasis after undergoing adenotonsillectomy, and both were completely free of psoriatic outbreaks after 16 months of follow-up. We conclude that tonsillectomy appears to be of benefit in the treatment of children with recurrent guttate psoriasis and recurrent streptococcal pharyngotonsillitis, and we hope that further investigation will be undertaken.     

One-off streptococcal serologic testing in young children with recurrent tonsillitis

OBJECTIVES: Recurrent acute tonsillitis in children under 4 years of age is usually viral, making antibiotic therapy inappropriate and the indication for tonsillectomy uncertain. Identifying those young children with bacterial infections is therefore important. The purpose of this study was to determine whether one-off streptococcal serologic testing is a useful tool in assessing recurrent acute tonsillitis in young children. METHODS: We performed a retrospective study of 45 children (35 male and 10 female) under the age of 4 years who were found by a staff otolaryngologist to have recurrent acute tonsillitis over a 5-year period and had one-off serologic testing for anti-streptolysin O titers and anti-deoxyribonuclease B levels. Data were collected by chart review. RESULTS: Three children (6.7%) had clearly positive titers for either one or both streptococcal antibodies. Children with negative serologic results were significantly less likely to have shown a significant response to antibiotic therapy for their acute episodes (26% versus 100%; p = .026). Nine children (20%) eventually underwent tonsillectomy, all of whom had negative serologic results. CONCLUSIONS: Anti-streptolysin O and anti-deoxyribonuclease B levels may aid clinical evaluation of recurrent acute tonsillitis in young children in differentiating between those cases due to group A beta-hemolytic Streptococcus and those that are viral in origin.     

Fewer symptoms occur in same-serotype recurrent streptococcal tonsillopharyngitis

BACKGROUND: Most patients with acute rheumatic fever report no antecedent pharyngitis. OBJECTIVE: To determine the clinical and microbiological characteristics of recurrent group A beta-hemolytic streptococcal (GABHS) tonsillopharyngitis. DESIGN: Prospective randomized trial. SUBJECTS: Symptoms were recorded and throat cultures were obtained at 4 to 6, 18 to 21, and 32 to 35 days following the start of treatment. A subset of 60 patients with subsequent GABHS episodes occurring were evaluated for a 0.2-or greater log rise in either antistreptolysin O or anti-deoxyribonuclease B titer to confirm a bona fide recurrence. RESULTS: Sixteen (27%) of 60 patients had recurrent GABHS tonsillopharyngitis of the same serotype that occurred 21 days or longer following the onset of the initial GABHS infection and was associated with a 0.2- or greater log rise in either antistreptolysin O or anti-deoxyribonuclease B titer, indicating bona fide recurrent infection; these recurrences all occurred within 55 days. Fewer patients with recurrent GABHS pharyngitis of the same serotype had headache (P =.02), sore throat (P =.006), fever (P =. 008), pharyngeal erythema (P<.001), pharyngeal edema (P<.001), pharyngeal exudate (P =.04), and adenitis (P =.03) compared with the initial episode. Chills, stomachache, scarlatina, tonsillar enlargement, and palatal petechiae were similar for both episodes. CONCLUSIONS: Fewer symptoms occur during recurrent GABHS pharyngitis of the same serotype compared with the initial infection. These patients may be less likely to seek physician attention, yet their infections put them at risk for sequelae.     

Adenoids and tonsils, indications for surgery and immunological consequences of surgery

Tonsillectomy and adenoidectomy procedures are among the oldest surgical procedures still performed today. Tonsils and adenoids are part of Waldeyer's ring, the basic function of which is antibody formation. Because of their location at the portal of entry of many airborne and alimentary antigens, the tonsils and adenoids often have been considered as the first line of defense against respiratory infections. Indications for adenoidectomy or tonsillectomy are to date still controversial. The two main indications for tonsillectomy are upper airway obstruction due to tonsillar hypertrophy and recurrent acute or chronic tonsillitis. Adenoid hypertrophy with upper airway or eustachian tube obstruction and recurrent acute or chronic adenoiditis or otitis media are main indications to perform an adenoidectomy. The possible immunological effects of tonsillectomy and adenoidectomy are still controversial. Some authors have found changes in immunoglobulin levels after tonsillectomy, while others failed to find significant changes. In a review of long-term follow-up studies, the authors showed that while tonsillectomy may lead to certain changes in the cellular and humoral immune system, these alterations are clinically insignificant and no increased frequency of immunomodulated diseases should be expected.     

Characterization of B-Cells in tonsils of patients diagnosed with pediatric autoimmune neuropsychiatric disorder associated streptococcus

ObjectiveTo determine if Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcus (PANDAS) patients demonstrate a significantly different number of B-Cells or markers of activity when compared to recurrent Group A Streptococcus or Obstructive Sleep Apnea patients.Study designProspective Cohort Study.Study settingAcademic University Hospital.MethodsTonsil tissue was collected from twenty-two patients in the operating room and organized into three groups. Ten clinically diagnosed PANDAS, six Group A Streptococcus and six Obstructive Sleep Apnea patients were included in this study. Each tissue sample was extracted with MSD Tris Lysis Buffer and protein lysates were analyzed for CD 19, B-Cell Activating Factor and B-Cell Activating Receptor by western blot methods.ResultsBased on ANOVA analysis, there was no significant difference in the expression of B-Cell Activating Factor, B-Cell Activating Receptor or CD 19 when comparing the three study groups by western blot analysis methods.ConclusionsIn this prospective cohort study, it appears that PANDAS patients do not demonstrate increased number of B-Cells, expression of B-Cell Activating Factor or B-Cell Activating Receptor when compared to Group A Streptococcus or Obstructive Sleep Apnea cohorts. As a result, further evaluation of the cell-mediated immune system is warranted to provide further insight into the pathophysiology of PANDAS. In addition, we must investigate if PANDAS patients only demonstrate increased B-Cell number or activity when undergoing an acute Tic/OCD exacerbation.     

The significance of recurrent tonsillitis in sickle cell disease

Forty-five patients with homozygous sickle cell disease who had tonsillectomy for recurrent tonsillitis, when compared with 45 matched controls with haemoglobin genotype AA, showed significant differences in the clinical manifestations and complications of recurrent tonsillitis between the two groups. Although throat swabs in the sickle cell group were mostly negative because they were on prophylactic penicillin, all tonsils harboured Streptococcus pneumoniae when cultured. This study suggests the tonsils to be the more specific source of pneumococcal infection that causes sytemic complications which increase morbidity and mortality in sickle cell disease. Although the sickle cell patients may be less clinically symptomatic with tonsillitis, the incidence of serious complications caused by pneumococcal infections, now shown to arise from the tonsils, is significant. Adenotonsillar hypertrophy is linked with an increased risk of a sleep apnoea which causes serious neurological complications such as cerebral infarction and stroke. Tonsillectomy has greatly reduced the incidence of complications from pneumococcal infections in the sickle cell group and should therefore be recommended for sickle cell patients taking prophylactic penicillin and still developing pneumococcal infections.     

Activity of budesonide on nasal neutrophilic inflammation and obstruction in children with recurrent upper airway infections. A preliminary investigation

OBJECTIVE: While it is widely accepted that inhaled glucocorticosteroids represent an effective treatment for allergic rhinitis, little is known on the specific effects of this therapeutic approach in other upper airway disorders of childhood. The aim of the study was to evaluate the improvement of clinical symptoms and changes in local cellular inflammatory reaction induced by budesonide inhalation suspension in children with recurrent nasal infections using budesonide inhalation suspension delivered by Rinowash, a nebulizer designed to treat upper airway structures. METHODS: In a randomized, controlled-open study, 14 children (5.88+/-0.56 years of age) with recurrent upper airway infections and chronic nasal obstruction were enrolled and randomly treated for 7-10 days either with budesonide inhalation suspension (250 microg/bidie) (nine patients) or with saline solution (five patients). Before and after treatment, inflammatory cells in nasal brushing and nasal symptom score were evaluated. RESULTS: Out of the nine patients treated with budesonide, two were excluded from the analysis because of acute respiratory infections requiring systemic antibiotic treatment. A significant decrease in nasal brushing neutrophil percentage was observed after treatment with budesonide (P=0.016) but not after saline solution treatment (P=1.00). No significant changes in nasal brushing mononuclear cell or eosinophil proportions were observed after treatment with budesonide inhalation suspension or saline solution (P=NS, each comparison). Treatment with budesonide, but not with saline solution, was associated with a significant reduction in nasal obstruction (P=0.016). CONCLUSIONS: These preliminary data indicate that short-term treatment with budesonide inhalation suspension, used for an indication out of label, may significantly reduce local neutrophilic inflammation and nasal obstruction in children with recurrent upper airway infections.     

The relationship of tonsillar hyperplasia and asthma in a group of asthmatic children

BACKGROUND: The decline of infections in childhood may contribute to the rising severity and prevalence of atopic disorders in developed countries. With this regard, we examined the relationship of frequent tonsillitis and consequent tonsillar hyperplasia with the development of asthma. METHODS: Sixty-seven asthmatic children (ages 3-14) who had no signs or symptoms of acute tonsillitis were included. The control group consisted of 92 randomly selected children who had no signs or symptoms of asthma or acute tonsillitis. Parents were interviewed about the incidence of tonsillitis diagnosed by physicians and history of tonsillectomy; tonsil sizes were evaluated by oropharyngeal inspection by the same observer using the Brodsky L. Scala. RESULTS: A statistically significant association is found between frequent tonsillitis and consequent tonsillar hyperplasia with the development of asthma. CONCLUSIONS: Our data suggests that recurrent tonsillitis is associated with a decline in the prevalence of asthma by inducing a Th 1 predominant immune response. Our findings are compatible with the hygiene hypothesis.     

Antibiotic therapy - a critical review (author's transl)]

The antibiotic management of tonsillitis, acute otitis media, sinusitis and bronchitis is critically reviewed. Tonsillitis due to Group A streptococci must be treated with penicillin for 10 days in order to prevent complications. Antibiotics should not be used locally in pharyngitis or tonsillitis. Tonsillectomy does neither reduce the incidence of streptococcal tonsillitis nor of rheumatic complications. Antibiotic cover for tonsillectomy is not indicated except in patients with rheumatic heart disease or in those with prosthetic heart valves. The indications for the prophylactic use of antibiotics in ear, nose and throat surgery are discussed.     

All snoring is not adenoids in young children

OBJECTIVE: To determine the prevalence of snoring in young children and to assess age, growth, previous surgery therapy, respiratory problems and sleep-related symptoms in relation to child's snoring, and to evaluate the relationship between child's snoring and parents' snoring and smoking. CHILDREN AND METHODS: A cross-sectional study evaluated 2100 children 1-6 years of age in Helsinki, Finland. Child's frequency of snoring on a five-point scale (never to every night) and age, height, weight and body mass index, previous adenotonsillectomies, tympanostomies, allergic rhinitis and respiratory infections were determined as was frequency of parental snoring and smoking. Sleep problems were determined based on Finnish or Swedish modified version of the sleep disturbance scale for Children. RESULTS: Of the 2100 eligible children, 1471 (71%) returned questionnaires. Children always or often snoring numbered 92 (6.3%), sometimes snoring, 183 (12.4%), and never or occasionally snoring, 1196 (81.3%). No difference in age (p=0.06) or gender (p=0.39) existed between snorers and non-snorers. History of previous adenotonsillectomies (p<0.001), allergic rhinitis (p<0.001), recurrent respiratory infections (p<0.001), and otitis media (p<0.001) were more common among snorers than among occasional or never-snorers. Nocturnal symptoms such as breathing problems, sleep hyperhydrosis, sleep-wake transition disorders, and daytime somnolence were associated with children's snoring. Frequency of children's snoring was also associated with parental snoring (p<0.001) and smoking (p<0.001). CONCLUSIONS: Snoring is common among young children and is associated with previous adenotonsillectomy, allergic rhinitis, respiratory infections, nocturnal symptoms, and parents' snoring and smoking. The high prevalence of snoring among children with adenotonsillectomy raises the question whether adenotonsillectomy alone is adequate treatment for snoring in young children.     

Cervical osteomyelitis. An unusual complication of tonsillectomy

Tonsillectomy is one of the most common operations performed by the otolaryngologist. Deep-neck infections are among the possible complications associated with this procedure. We encountered a case of osteomyelitis of the cervical spine occurring subsequent to an otherwise uncomplicated tonsillectomy. Although never previously reported with tonsillectomy to our knowledge, cervical osteomyelitis has been associated with other procedures and infections of the head, neck, and maxillofacial regions. Mechanisms that might explain this occurrence include direct extension via fascial planes, direct venous and lymphatic spread, and hematogenous dissemination from the contaminated surgical site. Treatment consisted of drainage and débridement of the infection, cervical immobilization, and long-term antibiotic administration. Healing was complete and cervical mobility and stability were normal at three months. Early recognition of this unusual complication of tonsillectomy is imperative to avoid potential neurologic sequelae.     

Intoxication syndrome concomitant with recurrent streptococcal tonsillitis and its correction

The objective of the present work was to study selected features of intoxication in the patients presenting with recurrent tonsillitis (RT) and managed by means of the combination of basal therapy with reamberine, a preparation showing the detoxication activity. A total of 70 patients with moderately severe recurrent streptococcal tonsillitis induced by infection with group A beta-hemolytic streptococci were available for the examination. Characteristics of endogenous intoxication were explored. The study has demonstrated that recurrent tonsillitis is associated with the development of the pronounced symptoms of endogenous intoxication (EI) as suggested by the enhanced leukocytic index of intoxication (LII) and the elevated levels of medium molecular weight molecules (MWM) with the simultaneous impairment of detoxication properties of albumin. Collectively, these changes are indicative of incompleteness of the pathological process that may be regarded as an unfavourable prognostic factor and suggests the risk of development of tonsillogenic pathology, its relapses, and chronization of the process. Taken together, these findings indicate the necessity of developing novel approaches to the treatment of recurrent tonsillitis with special reference to the use of pharmaceutical products possessed of detoxication activity. Reamberine introduced in the combined treatment of RT was shown to decrease the severity of intoxication as confirmed by normalization of LII and MWM levels as well as the improvement of detoxication properties of albumin. It is concluded that therapeutic efficacy of reamberine opens up wide prospects for its clinical applications.