Fibromyalgia syndrome in young children: onset at age 10 years and younger.

OBJECTIVE: To report our experience of fibromyalgia syndrome (FMS) in young children with onset at age 10 years and younger as compared to older children. METHODS: Clinical and laboratory data were reviewed in all patients that had been diagnosed with FMS between November 1994 and March 2003. Patients with onset above the of age 18 years, and patients with FMS and concomitant rheumatic diseases were excluded from this study. The study population included two groups: group "A", young children with onset at age 10 years and under and group "B", children with onset above 10 years old. A questionnaire was used at follow-up visits or by telephone interview to evaluate the outcome. RESULTS: There were 148 children with the diagnosis of FMS (based on ACR criteria), of these 46 children in group A and 102 children in group B. The mean age at onset and mean age at diagnosis were 7.5 years and 10 years in group A, and 13.2 years and 14.5 years in B, respectively. The mean interval between the age of onset and the age at diagnosis was 32 months in group A, and 18 months in group B (p= 0.007). There was a predominance of female gender and Caucasian ethnicity in both groups. Diffuse aching was reported in all patients in both groups. Stiffness, subjective joint swelling, abdominal pain and initial presentation on wheelchair were found more frequently in group A, compared with group B (p= 0.03, 0.001, 0.01, 0.03 respectively). The mean count of tender points at diagnosis was higher in group A, compared with group B (15.3 vs. 14.2, p = 0.004). The differences of other clinical features and laboratory tests in both groups were not statistically significant. Thirty-six patients in group A (78%) and 83 in group B (81%) were available for one or more follow-up visits and/or telephone interview. The mean follow-up period was 14 months in group A, and 19 months in group B (p value = 0.3). There was no difference in the type of treatment or outcome in both groups. CONCLUSION: FMS in young children of 10 years old and younger is frequently under-recognized. As compared with the older group, stiffness, subjective joint swelling, abdominal pain, initial presentation on wheelchair and a higher mean count of tender points at diagnosis were significantly more common in the younger age group. However, the type of medications used and outcome were similar in both groups. Prospective studies with large patient population are needed to clarify these findings.

Muscular dysfunction elicited by creep of lumbar viscoelastic tissue.

The biomechanics, histology and electromyography of the lumbar viscoelastic tissues and multifidus muscles of the in vivo feline were investigated during 20 min of static as well as cyclic flexion under load control and during 7 h of rest following the flexion. It was shown that the creep developed in the viscoelastic tissues during the 20 min of static or cyclic flexion did not fully recover over the 7 h of following rest. It was further seen that a neuromuscular disorder with five distinct components developed during and after the static and cyclic flexion. The neuromuscular disorder consisted of a decreasing magnitude of reflexive EMG from the multifidus upon flexion as well as of superimposed spasms. The recovery period was characterized by an initial muscle hyperexcitability, a slowly increasing reflexive EMG and a delayed hyperexcitability. Histological data from the supraspinous ligament demonstrate significant increase (x 10) in neutrophil density in the ligament 2 h into the recovery and even larger increase (x 100) 6 h into the recovery from the 20 min flexion, indicating an acute soft tissue inflammation. It was concluded that sustained static or cyclic loading of lumbar viscoelastic tissues may cause micro-damage in the collagen structure, which in turn reflexively elicit spasms in the multifidus as well as hyperexcitability early in the recovery when the majority of the creep recovers. The micro-damage, however, results in the time dependent development of inflammation. In all cases, the spasms, initial and delayed hyperexcitabilities represent increased muscular forces applied across the intervertebral joints in an attempt to limit the range of motion and unload the viscoelastic tissues in order to prevent further damage and to promote healing. It is suggested that a significant insight is gained as to the development and implications of a common idiopathic low back disorder as well as to the development of cumulative trauma disorders.

Renal involvement in juvenile rheumatoid arthritis: report of two cases.

Renal involvement is a rare occurrence in juvenile rheumatoid arthritis (JRA). We report on two JRA patients with kidney disease. The first was a 14-year-old African-American female with a 12-month history of polyarthritis. On presentation she was found to have an ESR of 127 mm/h and a positive ANA, rheumatoid factor (RF), perinuclear antineutrophil cytoplasmic antibodies (pANCA), haematuria, proteinuria with normal BUN and creatinine. Renal biopsy showed focal segmental glomerulosclerosis. Her renal function deteriorated to end-stage renal failure requiring dialysis within a few months, despite aggressive treatment with steorids and monthly i.v. pulses of cyclophosphamide. The second patient presented with a 6-week history of polyarthritis and intermittent fever, and had a salmon-coloured evanescent rash. On presentation his laboratory evaluation was significant for elevated ESR and negative ANA, RF and ANCA tests. Within 8 months the patient had developed a persistent microscopic haematuria. Renal biopsy showed mild mesangial glomerulonephritis. On low-dose methotrexate therapy his JRA went into remission and his renal function remained normal. The haematuria persisted for 1 year and then resolved spontaneously. This is the first time that focal segmental glomerulosclerosis and mesangial glomerulonephritis have been described in JRA. Although the association may be just coincidental, further studies are needed to define the role of JRA in these renal conditions. In patients with JRA, urinalysis and renal function should be routinely monitored.

Intravenous immunoglobulin therapy for children with Stevens-Johnson syndrome.

OBJECTIVE: To review the experience with intravenous immunoglobulin (IVIG) therapy in patients with Stevens-Johnson syndrome (SJS) in our institution. METHODS: All charts of patients with SJS admitted to Children's Hospital between November 1988 and June 1998 were reviewed. RESULTS: Twelve patients with SJS were detected. There were 8 males and 4 females, with a mean age 6 years (range 10 mo to 17 yrs). All patients presented with high fever and cutaneous and mucous membrane changes, and the diagnosis SJS was confirmed by a dermatologist. Of the 12 patients with SJS, 7 were treated with IVIG, 2 with corticosteroids, and 3 with supportive care. IVIG was administered in a single infusion at 1.5-2 g/kg, and was given on an average of hospital day 3 (range 1-8 days). The average duration of fever was 8 days (range 3-14) in the IVIG treated patients compared to 14 days (range 6-20) in the non-IVIG treated group (p = 0.06). The mean hospital stay was 12 days (range 4-22) for the patients treated with IVIG and 15 days (range 6-25) for the non-IVIG treated group (p = 0.5). No toxicity was observed with IVIG therapy. CONCLUSION: Duration of fever was shortened in patients treated with IVIG, although statistical significance was marginal. The hospital stay was slightly shortened in patients treated with IVIG; however, statistical significance was not reached. Prospective and controlled, multicenter studies are needed to further investigate these preliminary findings.

Fibromyalgia syndrome: experience in a pediatric rheumatology clinic.

OBJECTIVE: To report our experience of fibromyalgia syndrome (FMS) in pediatric rheumatology clinic settings. METHODS: Clinical and laboratory data were reviewed in all patients with FMS between March 1992 and March 1996. Patients with FMS and an underlying rheumatic disease were excluded from the study. At presentation and follow-up visits, all patients had a tender points (TP) count that was conducted by thumb palpation. Both the children and their parents were questioned concerning the presence of widespread pain or aching. All the patients fulfilled the ACR criteria for the diagnosis of primary FMS. All children were evaluated by a protocol that included relevant information on FMS. Telephone survey questionnaires were used for patients who missed some of their follow-up visits. RESULTS: There were 59 children (47 F and 12 M) diagnosed with primary FMS. The mean age at onset was 13.7 years, and the mean age at diagnosis was 15.5 years. The mean duration of follow-up was 18.3 months. Diffuse aching was reported in 57 patients (97%), headaches in 45 (76%), and sleep disturbances in 41 (69%). Less common were stiffness in 17 (29%), subjective joint swelling in 14 (24%), fatigue in 12 (20%), abdominal pain in 10 (17%), and joint hypermobility and depression in 8 (14%) and 4 (7%) patients, respectively. The mean ESR was 15 mm/h, RF was negative in all patients, and ANA was positive (mean titer 1:160) in 17 patients. The mean initial TP count was 14.6. Nine patients were not available for follow-up. There were 50 patients available for follow-up and survey analysis, and of these 30 (60%) had improved, while 18 (36%) remained unchanged, and 2 (4%) became worse when compared with initial presentation. At the end of study follow-up, 37 patients (74%) were still taking medication (20 of them daily). Out of 25 patients whose TP counts were available at the end of follow-up, the mean TP dropped from 14.12 to 12.04 (p = 0.09) for the total group, and 14.05 to 10.84 (p < 0.01) for the patients who had improved. 22 out of 30 patients in the improved group and 7 out of 20 in the unchanged or worse group had continued active exercise programs (p < 0.001). CONCLUSION: The clinical spectrum of FMS in children is similar to that of adults but with better outcomes. The TP count correlates with clinical status only in patients who had improved. Active exercise programs seem to correlate with better outcomes. Prospective and larger patient population studies, and a longer follow-up of children with FMS are needed to clarify these findings.

Infantile Henoch-Schönlein purpura.

Henoch-Schönlein purpura is a common cause of vasculitis in children. This condition is unusual in infants and children younger than 2 years. We describe a 4-month-old infant with infantile Henoch-Schönlein purpura and review the clinical spectrum, differential diagnoses, and the histopathologic features of the disease. Its relations to Henoch-Schönlein purpura in older children are discussed.

Antinuclear antibody (ANA) and ANA profile tests in children with autoimmune disorders: a retrospective study.

The study objective was to determine the clinical value of positive antinuclear antibody (ANA) and ANA profile tests in children with autoimmune disorders. A retrospective chart review was carried out of all patients under 18 years of age with a positive ANA test (HEp-2 cell substrate, titre > or =1:40) and ANA profile (ELISA) referred to the paediatric rheumatology service at the authors' institution between 1992 and 1996. Of 245 children with a positive ANA test, 134 (55%) had an autoimmune disease, including juvenile rheumatoid arthritis (n = 49), systemic lupus erythematosus (SLE) (n = 40) and others (n = 45). The remaining 111 patients did not have identifiable autoimmune diseases. Patients with autoimmune disorders had significantly higher ANA titres of > or = 1:160 (chi2 = 16, P<0.0001). In addition, of the 245 patients with a positive ANA test, 86 had an ANA profile performed; this was positive in 32 and negative in 54. All 32 patients with a positive ANA profile (100%) had an autoimmune disorder, compared to 22 (41%) of 54 with a negative ANA profile who had autoimmune disorders. Of 22 SLE patients with a positive ANA profile, 16 (73%) had positive anti-dsDNA and 15 (68%) had positive anti-Sm and positive anti-RNP. A positive ANA profile correlated strongly with an ANA titre > or = 1:640 (chi2 = 5.7 , P<0.02). The study demonstrated that only 55% of children with a positive ANA test had a definitive diagnosis of autoimmune disorder. These children tend to have higher ANA titres of > or =1:160. However, a positive ANA profile was strongly correlated with an ANA titre > or =1:640 and highly indicative of an autoimmune disorder (100%). We suggest that in order to reduce cost, an ANA profile should not be performed on all patients with positive ANA, but reserved for those with an ANA titre of > or =1:640 and/or those with a high clinical index of suspicion for autoimmune disorder, especially SLE.

Etanercept in children with polyarticular juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group.

BACKGROUND: We evaluated the safety and efficacy of etanercept, a soluble tumor necrosis factor receptor (p75):Fc fusion protein, in children with polyarticular juvenile rheumatoid arthritis who did not tolerate or had an inadequate response to methotrexate. METHODS: Patients 4 to 17 years old received 0.4 mg of etanercept per kilogram of body weight subcutaneously twice weekly for up to three months in the initial, open-label part of a multicenter trial. Those who responded to treatment then entered a double-blind study and were randomly assigned to receive either placebo or etanercept for four months or until a flare of the disease occurred. A response was defined as an improvement of 30 percent or more in at least three of six indicators of disease activity, with no more than one indicator worsening by more than 30 percent. RESULTS: At the end of the open-label study, 51 of the 69 patients (74 percent) had had responses to etanercept treatment. In the double-blind study, 21 of the 26 patients who received placebo (81 percent) withdrew because of disease flare, as compared with 7 of the 25 patients who received etanercept (28 percent) (P=0.003). The median time to disease flare with placebo was 28 days, as compared with more than 116 days with etanercept (P<0.001). In the double-blind study, there were no significant differences between the two treatment groups in the frequency of adverse events. CONCLUSIONS: Treatment with etanercept leads to significant improvement in patients with active polyarticular juvenile rheumatoid arthritis. Etanercept is well tolerated by pediatric patients.

Childhood-onset systemic lupus erythematosus: a comparative study of African Americans and Latin Americans.

This study compared the clinical and serologic features in two different ethnic groups of patients with childhood-onset systemic lupus erythematosus (SLE). One hundred seventy-one SLE patients comprised the study population; 61 (55 girls and 6 boys) were African American with age at onset of 13 +/- 2.9 years, and 110 (97 girls and 13 boys) were Latin American (Colombian) with age at onset of 13 +/- 3.2 years. Clinical, demographic, and laboratory data were obtained by chart review using a standard data collection form. African-American patients more commonly manifested discoid skin lesions, malar rash, pulmonary fibrosis, and pleuritis, and less commonly manifested photosensitivity, livedo reticularis, and vascular thrombosis than did Latin Americans. In addition, there was a higher frequency of anti-dsDNA, anti-Sm, anti-RNP, and anti-Ro positivity among African-Americans compared with Latin-American patients. These results suggest the presence of ethnic differences in the clinical expression of SLE.

Membranous nephropathy associated with childhood sarcoidosis.

Sarcoidosis is a chronic multisystemic granulomatous disease of unknown etiology. It is relatively rare in children. Renal involvement in sarcoidosis is described less commonly than other organ involvement such as pulmonary, eye, musculoskeletal, and skin. We report a 13-year-old girl with sarcoidosis and nephrotic syndrome. Renal biopsy showed findings of membranous nephropathy. She received intravenous pulse methylprednisolone and oral cyclophosphamide with resolution of the symptoms of fever and edema, and improvement of the proteinuria. Her condition is stable with no progression of her renal disease. To the best of our knowledge, this is the first report of membranous nephropathy associated with childhood sarcoidosis.

Low-dose methotrexate in the treatment of severe juvenile rheumatoid arthritis and sarcoid iritis.

OBJECTIVE: To assess the efficacy of low-dose oral methotrexate (MTX) therapy for children with severe iritis. METHODS: MTX in a weekly dose of 7.25 to 12.5 mg/m2 was administered orally to four patients (two with juvenile rheumatoid arthritis [JRA] and two with sarcoidosis) with severe iritis not adequately controlled by topical and systemic corticosteroid therapy. The treatment was initiated with half of the total dose and increased every 2 weeks until the final dose was reached. Iritis was graded from 0 to +4 according to the density of cells in the anterior chamber of the eye. RESULTS: There were three girls and one boy with a mean age of 10.5 years. Two patients were African American and two were Caucasian. The mean age at onset of iritis was 6 years. The mean duration of MTX therapy was 28.8 months. Significant improvement was noted in two of the four patients in ocular inflammation, demonstrated by reduction of cell density from +4 to +1. Two patients had a mild improvement of the iritis. However, corticosteroids were significantly reduced in all patients. One patient was completely off steroids within 30 months of MTX therapy. In the remaining three cases, the steroid dose was successfully tapered from 0.82 mg/kg/d to 0.15 mg/kg/d (mean doses) within a mean duration of 20 months. No side effects were observed with MTX therapy. CONCLUSION: Low-dose MTX therapy was effective and safe, and displayed steroid-sparing properties in four children with severe iritis.

Anticardiolipin antibodies in childhood rheumatic disorders.

Anticardiolipin antibodies (aCL) have been reported to occur in a wide variety of autoimmune and non-autoimmune disorders in adults. Our objective was to investigate the prevalence and isotype distribution of aCL and its relationship with the features of antiphospholipid syndrome (APS) in childhood rheumatic disorders. Between November 1995 and May 1996, all patients who visited our paediatric rheumatology clinic whose guardians signed a consent form participated in the study. The study population included 106 patients (36 systemic lupus erythematosus (SLE), 28 juvenile rheumatoid arthritis (JRA), 11 fibromyalgia, 7 sarcoidosis, 5 dermatomyositis, 3 rheumatic fever (RF), 3 vasculitis, 2 scleroderma, and 11 miscellaneous). aCL measurements were performed by enzyme linked immunoabsorbent assay (ELISA). All patients were carefully evaluated for symptoms and signs of APS. Eighteen of the 106 patients (17%) were tested positive for one or more of the three aCL isotypes. In SLE, aCL were found positive in 13 of 36 (37%); in JRA 2 of 28 (7%); in sarcoidosis 2 of 7; and in RF 1 of 3. aCL of IgG isotype were found positive in 16 patients (11 SLE, 2 sarcoidosis, 2 JRA, and 1 RF). This isotype was usually detected at low titers (16-24 GPL). aCL of IgM isotype were found positive in five patients (2 sarcoidosis, 2 SLE, 1 JRA), and aCL of IgA isotype were found positive in only three patients (2 SLE, 1 sarcoidosis). Clinical features of APS were rarely seen in our SLE population and were not associated with the presence of aCL. None of the patients in the other groups exhibited any clinical manifestations of APS. In conclusion, aCL were found in 37% of our childhood SLE patients as compared with only 7% in JRA. These were mostly aCL of IgG isotype of low titers and therefore were not associated with the main features of APS. Prospective studies with a larger sample size may be needed to ascertain the exact prevalence and clinical significance of aCL in childhood-onset SLE.

Sarcoidosis: a pediatric perspective.

Childhood sarcoidosis is a rare multisystemic granulomatous disease of unknown etiology. The clinical presentation can vary greatly depending upon the organs involved. Two distinct forms of sarcoidosis exist in children. Older children usually present with a multisystem disease similar to the adult manifestation, with frequent hilar lymphadenopathy and pulmonary infiltration. Early-onset childhood sarcoidosis is a unique form of the disease characterized by the triad of rash, uveitis, and arthritis in patients presenting before age 4 years. The diagnosis of sarcoidosis is confirmed by demonstrating a typical noncaseating granuloma on a biopsy specimen. The current therapy of choice for childhood sarcoidosis with multisystem involvement is corticosteroids. Methotrexate given orally in low doses is effective and safe and has steroid-sparing properties.

Sickle cell anemia with systemic lupus erythematosus: response to hydroxyurea therapy.

PURPOSE: To report the efficacy of hydroxyurea (HU) in a patient with sickle cell anemia (SCA) associated with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: An unusual association of SCA with SLE occurred in a 14-year-old black girl. Her medical history was significant for repeated vasoocclusive crises requiring repeated hospitalizations and transfusions, acute chest syndrome, hyperhemolytic crises, multiple transfusions resulting in iron overload, gall stones, avascular necrosis, and significant psychosocial problems. Her lupus activity was controlled with oral prednisone and hydroxychloroquine. Treatment with oral HU was instituted at an initial dose of 20 mg/kg with gradual increment to a maximum of 25 mg/kg daily. RESULTS: A dramatic clinical improvement was noted with HU therapy with no episode of pain crisis or hospitalization for 5 months. There was an increase in fetal hemoglobin (HbF) to 20.9% and mean corpuscular volume to 114.5 fl, but her Hb level remained steady at 7.5 g/dl. No toxicity was noted with HU therapy. In addition, a significant change was also observed in her school performance, social activities, and general quality of life. CONCLUSIONS: HU therapy may be beneficial and safe and should be considered for other patients who have SCA with SLE.

Septic arthritis in children.

Because of its seriousness, septic arthritis should be considered early in the differential diagnosis of any child presenting with joint inflammation. Physicians who care for children should be aware of the early signs and symptoms of septic arthritis and be aggressive about establishing the diagnosis so that treatment is not delayed. Early orthopedic consultation and a low threshold for performing arthrocentesis are prudent. Prolonged and appropriate antimicrobial therapy is warranted to achieve optimal results.