Unravelling the clinical heterogeneity of undefined recurrent fever over time in the European registries on Autoinflammation.

BACKGROUND: Systemic autoinflammatory disorders (SAIDs) represent a growing spectrum of diseases characterized by dysregulation of the innate immune system. The most common pediatric autoinflammatory fever syndrome, Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA), has well defined clinical diagnostic criteria, but there is a subset of patients who do not meet these criteria and are classified as undefined autoinflammatory diseases (uAID). This project, endorsed by PRES, supported by the EMERGE fellowship program, aimed to analyze the evolution of symptoms in recurrent fevers without molecular diagnosis in the context of undifferentiated AIDs, focusing on PFAPA and syndrome of undifferentiated recurrent fever (SURF), using data from European AID registries. METHODS: Data of patients with PFAPA, SURF and uSAID were collected from 3 registries including detailed epidemiological, demographic and clinical data, results of the genetic testing and additional laboratory investigations with retrospective application of the modified Marshall and PRINTO/Eurofever classification criteria on the cohort of PFAPA patients and preliminary SURF criteria on uSAID/SURF patients. RESULTS: Clinical presentation of PFAPA is variable and some patients did not fit the conventional PFAPA criteria and exhibit different symptoms. Some patients did not meet the criteria for either PFAPA or SURF, highlighting the heterogeneity within these groups. The study also explored potential overlaps between PFAPA and SURF/uAID, revealing that some patients exhibited symptoms characteristic of both conditions, emphasizing the need for more precise classification criteria. CONCLUSIONS: Patients with recurrent fevers without molecular diagnoses represent a clinically heterogeneous group. Improved classification criteria are needed for both PFAPA and SURF/uAID to accurately identify and manage these patients, ultimately improving clinical outcomes.

Modified regimen of etanercept for tumor necrosis factor receptor associated periodic syndrome (TRAPS) like illness.

BACKGROUND: TRAPS, an autosomal dominant autoinflammatory disorder occurs due to mutations of the TNFRSF1A gene. Mutation negative TRAPS (TRAPS like illness) is also known. Anti TNF molecules (etanercept) is the mainstay of therapy. CASE CHARACTERISTICS: A 11-year-old boy with a 5 year clinical profile indicative of a TRAPS like illness and with negative mutation studies is described. He has been followed up for nearly 2 years after starting etanercept. OUTCOME: He had sustained response to etanercept which has subsequently been titrated (0.4 mg/kg subcutaneously every 23-24 days) to keep him symptom free. MESSAGE: Mutation negative cases of TRAPS can be diagnosed with a high index of suspicion. Treatment with etanercept is expensive but possibly intervals between doses could be titrated to reduce cost.

Thalidomide for systemic onset juvenile idiopathic arthritis.

Systemic onset juvenile idiopathic arthritis (SOJIA) is the most common autoimmune auto inflammatory disease in childhood. A sizeable number of these patients run a recalcitrant disease course, resistant to the conventional line of management, ultimately resulting in permanent disability from joint destruction, local growth deformities or iatrogenic side effects. The new biological agents although very effective, are beyond the affordability of most in our country. Thalidomide, a cheaper option has been shown to be very effective in the disease control of patients with SOJIA. We report three Indian children with a chronic refractory course of SOJIA, all of whom had failed conventional line of treatment but improved with thalidomide.

Joint hypermobility and growing pains in school children.

OBJECTIVES: To study the association between growing pains (GP) and joint hypermobility (HM ), children aged 3-9 were examined for the coexistence of HM and GP. METHODS: The study group consisted of 433 children (219 boys, 214 girls; age range 3-9 years) from one public school in Mumbai, India. In the assessment of HM, the Beighton criteria were used. Any child who met > or = 5/9 criteria was considered to have HM. Children were considered to have GP if they fulfilled the Petersons criteria, namely the pains were bilateral, intermittent non-articular pains involving the lower limbs; typically occurring during late afternoons or evenings with a normal physical examination and normal laboratory parameters whenever performed. The assessment of HM and GP were carried out independently. Children with bilateral knee hypermobility were also evaluated for the occurrence of GP. RESULTS: Of the 433 children, 177 (40.8%) were found to have HM and 122 (28.1%) GP; 75 (61.4%) of the 122 with GP had HM and 75 (42.3%) of the 177 with HM had GP. Using chi square statistical analysis, joint hypermobility and GP were found to be highly associated. Knee hypermobility also showed significant statistical association with GP. CONCLUSION: This study suggests that there is a strong association between joint hypermobility and GP in schoolchildren. It is possible that joint hypermobility may play a part in the pathogenesis of GP. More studies are needed to establish the clinical significance of this association.

Joint hypermobility in Indian children.

OBJECTIVES: To study the prevalence of joint hypermobility in children from Mumbai, India and to study its association with malnutrition. METHODS: In a cross-sectional field study from September '02 to February '03 in Mumbai, 829 children of the lower urban socio-economic strata, between 3 and 19 years of age were evaluated independently by two observers for hypermobility using the Beighton 9-point scoring system. A score of >or= 4/9 was considered positive. Their nutritional status was stratified using standard Indian growth charts and hypermobility was quantified in various nutritional groups. Musculoskeletal symptoms were assessed by a questionnaire given to parents. Standard tests of significance (Chi square test, p<0.05-significant) were applied. RESULTS: 58.7% of the population studied, had a Beighton score >or= 4/9. There was a declining prevalence of joint hypermobility noted with increasing age. Near equal sex incidence was noted. A higher incidence of finger signs was noted in comparison to elbow hyperextension, knee hyperextension and hands-to-floor. 26% of the hypermobile population had musculoskeletal symptoms as compared with 17.2% of the non-hypermobile population (p<0.05). A positive Beighton score was found in 452/734 (61.5%) children with Grade 3 and 4 malnutrition in comparison to 35/95 (36.8%) children with normal nutrition or mild grades (Grade 1 and 2) of malnutrition (p<0.05). In the group with Grade 3 and 4 malnutrition, 26.1% of those hypermobile had musculoskeletal symptoms in comparison to 17.7% of their non-hypermobile counterparts (p<0.05). CONCLUSIONS: In our study population: 1. A high prevalence of hypermobility using Beighton's score was noted; 2. Finger signs of the Beighton score were more common than the other signs; 3. Moderate and severe malnutrition were associated with hypermobility; 4. Musculoskeletal symptoms were linked to joint hypermobility; 5. Moderate and severely malnourished hypermobile children were more likely to have musculoskeletal symptoms as compared to their non-hypermobile counterparts.

Unusual neurologic manifestations (I): Parkinsonism in juvenile SLE.

A girl with neuropsychiatric lupus demonstrated Parkinsonian features soon after commencing risperidone. The single photon emission computed tomography scan showed hyperperfusion of the basal ganglia. Symptoms abated with the addition of dopaminergic agents to immunosuppressive therapy. The literature on juvenile Parkinsonism in lupus has been reviewed.

Mycoplasma pneumonia with antiphospholipid antibodies and a cardiac thrombus.

A case is reported of a four-year old child with mycoplasma pueumonia with a left atrial thrombus secondary to aPL antibodies. He was anticoagulated and the thrombus resolved in six months.

Haddad syndrome--congenital central hypoventilation associated with Hirschsprung's disease.

The combination of Congenital Central Hypoventilation with Hirschsprung's disease belongs to the family of diseases now designated as Neurocristopathies. The authors report a polysomnographically documented case and review literature on this disorder.

Initial evaluation of a child with arthritis--an algorithmic approach.

Arthritis is one of the less common, yet challenging problems that may confront a pediatrician. The potential pathology is diverse ranging from the benign with a good prognosis to the serious and ultimately fatal. From a spot diagnosis to conditions that evolve over time, few other conditions challenge and stimulate the clinical acumen. Several diagnoses can be made clinically with the laboratory investigations providing additional support. An approach through which the clinician seeks answers through a logical sequence of questions is presented to help shortlist the possible diagnosis.

Typhoid hepatitis in children.

Liver involvement is commonly observed in patients with typhoid fever. However, a hepatitis-like picture with fever and jaundice is unusual and infrequently reported in the paediatric literature. Our aim was to characterize the clinical picture, biochemical features, and prognosis of typhoid hepatitis. One hundred cases of typhoid fever (age 0 to 12 years), proven by positive blood cultures to Salmonella typhi, were studied with special reference to hepatic dysfunction. Of these, eight patients were found to have hepatitis during the course of their illness. All had high fever, tender hepatomegaly, elevated serum bilirubin (in the range of 2.5-5.8 mg/dl), and elevated serum alanine transaminase levels (in the range 100-620 IU/l). All the eight patients showed complete clinical and biochemical recovery in response to appropriate antibiotics. The clinical picture of typhoid hepatitis frequently mimics acute viral hepatitis. In tropical areas, the differential diagnosis of a child presenting with fever and jaundice should include typhoid hepatitis.

Proximal femoral focal deficiency (PFFD).

A 1-year-old child with proximal femoral focal deficiency (PFFD) is presented. The clinical spectrum and associated abnormalities is described and the diagnosis and management of this entity is discussed.