R. Topaloglu

Familial Mediterranean fever in children: report of a large series and discussion of the risk and prognostic factors of amyloidosis

Abstract Familial Mediterranean fever (FMF) is a genetically transmitted disease characterized by recurrent attacks of fever and serositis. The most important complication of this disease is the development of amyloidosis. We present our analysis of 425 FMF patients without and 180 with amyloidosis (123 FMF having amyloidosis type I and 57 FMF having amyloidosis type II). The male/female ratio was higher in the amyloidosis population (111/69) when compared to the FMF population (225/200) (P = 0.048). Consanguinity rate was the same among FMF and amyloidosis groups. However, a family history of amyloidosis was significantly more frequent in the amyloidosis group (P = 0.00001). Multivariate analysis has revealed that in FMF patients, the presence of a family history of amyloidosis plus consanguinity has a 6.04 fold increased risk of amyloidosis (P < 0.0001). The 5-year chronic renal failure free survival was 43.1% and 18.7% in type I and type II amyloidosis, respectively. The time interval to develop chronic renal failure after the development of amyloidosis was 4.8 in type I and 3.0 years in type II, respectively. We found ten cases of Henoch-Schönlein Purpura and nine of polyarteritis nodosa among our patients. The significance of the association between FMF and vasculitis awaits to be clarified. Among the FMF patients put on colchicine therapy (435), only 10 (2.3%) have developed amyloidosis confirming that this drug protects from amyloidosis. Conclusion Since the presence of a familial history of amyloidosis has been defined as the most important risk factor in the development of amyloidosis, we suggest that additional genetic factors may be operative in the development of amyloidosis.

A multicenter study of patients with adult-onset Still’s disease compared with systemic juvenile idiopathic arthritis

Adult-onset Still’s disease (AOSD) has often been regarded as the adult spectrum of systemic juvenile idiopathic arthritis (sJIA). The present study aims to compare the clinical and laboratory features, the disease course and the response to treatment in patients having AOSD with those having sJIA. Retrospective review of all available data that were filled out by adult and paediatric rheumatologists from six centers using a standard data extraction form was performed. A total of 95 patients with AOSD and 25 patients with sJIA were recruited for the study. The frequency of fever, rash, myalgia, weight loss and sore throat was higher in patients with AOSD. The pattern of joint involvement differed slightly. Laboratory findings were similar in both groups, except that liver dysfunction and neutrophilia were more common among adults. A multiphasic pattern dominated the childhood cases, whereas the most frequent course was a chronic one in adults. Corticosteroids and methotrexate were the most commonly employed therapy; however, chloroquine was another popular therapy in the adult group. We showed a difference in the rate of clinical and laboratory features between patients with AOSD and those with sJIA. AOSD and sJIA may still be the same disease, and children may simply be reacting differently as the result of the first encounter of the putative antigens with the immune system.

Plasma lipids and lipoproteins in juvenile chronic arthritis

SummaryAltered levels of high density lipoprotein (HDL), low density lipoprotein (LDL), and very-low density lipoprotein (VLDL), as well as apolipoproteins have been previously described in rheumatoid arthritis patients. We have attempted to evaluate the serum triglyceride, total cholesterol, cholesterol in DHL, LDL, apolipoprotein A1 (apo-A1) and apolipoprotein B (apo-B) levels in juvenile chronic arthritis (JCA) and to correlate them with CRP and ESR in the active and non-active stages of JCA. A total of 37 children who fulfilled ARA criteria for the diagnosis of JCA were studied. There were 18 girls and 19 boys. Age range was 2.5–16 years with a mean of 9.5. The mean duration of disease was 1.8 years. Nineteen patients were accepted to have active disease. Eighteen age and sex matched healty children served as controls. Apo-A1 was significantly lower in the active JCA group when compared to inactive patients and healthy controls (both p<0.05). There were significant inverse correlations between apo-A1 and both ESR and CRP levels in these patients (r=0.67, p<0.05 and r=−0.61, p<0.–05, respectively). Although mean LDL levels were numerically lower in the JCA patients (67.2 mg/dl in the active and 68.6 mg/dl in the inactive patients) the difference with healthy controls (91.7 mg/dl) was not statistically significant. There was no significant differences in regard to triglyceride, total cholesterol, cholesterol in HDL, and apo-B levels between neither of the groups. We conclude that JCA patients have a dyslipoproteinaemic state with already altered metabolism of lipids at different stages of the chronic inflammation from active to inactive disease.

Pulmonary Haemorrhage in a 6-Year-Old Boy with Henoch-Schonlein Purpura

Abstract Henoch–Scho¨nlein purpura (HSP) is the most common vasculitis in children. It is a multisystemic disease but pulmonary haemorrhage is extremely rare. We present the case of a 6-year-old boy with Henoch–Scho¨nlein purpura, pulmonary haemorrhage and severe renal involvement. The patient responded to a combination of intravenous methylprednisolone and cyclophosphamide. A review of the literature revealed that young age may be a good prognostic sign and that immunosuppressive drugs and supportive management are essential in the treatment. Renal biopsy is helpful in the differential diagnosis of HSP-mimicking pulmonary vasculitic syndromes. Combining cyclophosphamide with glucocorticoids may improve the outcome in severe HSP cases with pulmonary haemorrhage.

Survey of Factor V Leiden and Prothrombin Gene Mutations in Systemic Lupus Erythematosus

Abstract The two most common hereditary risk factors for thrombosis are factor V Leiden mutation and a prothrombin gene mutation. There is indeed a thrombotic tendency in patients with systemic lupus erythematosis (SLE) and it is not always associated with antiphospholipid antibodies. We aimed to determine the relationship between both factor V Leiden and prothrombin gene mutations and SLE. Using polymerase chain reaction (PCR) the factor V Leiden and prothrombin gene mutations were evaluated in 55 patients (20 children and 35 adults) with SLE. Although seven patients were found to have factor V Leiden mutation in the heterozygous state, two had the heterozygous G→A (20210) prothrombin gene mutation. Although one had these two mutations concurrently, these two patients did not have thrombosis. The factor V Leiden mutation frequency (12.7%) was higher than that of our general population (7.1%). On the other hand, seven of the patients with SLE had a thrombotic event. Although of these seven, four (57%) had factor V Leiden mutation, three (43%) had no mutation. Of 48 patients with no thrombotic history, only three had the factor V mutation (6.25%). The prevalence of the factor V Leiden mutation in SLE patients with and without thrombosis was significantly different by Fisher’s exact test (p<0.05). The risk of venous thrombosis in patients with factor V Leiden increased threefold compared to that in those without factor V Leiden mutation (odds ratio 20.1; CI 2.99–133.6). Although factor V Leiden mutation seems to play a role in the development of venous thrombosis in SLE, the development of thrombosis in SLE is multifactorial.

The role of apoptosis in childhood Henoch-Schonlein purpura.

AbstractThe pathogenesis of vasculitis is complex and is yet to be fully elucidated, although it is known that inflammatory cells play a major role. Dysregulation of apoptosis and defective clearance of inflammatory cells could lead to the persistence of inflammation and excessive tissue injury. In this study we aimed to investigate Fas (CD95) and apoptosis on peripheral blood (PB) neutrophil and lymphocytes in Henoch–Schonlein purpura, both in the acute phase and after resolution to determine the role of apoptosis in this self-limited vasculitis. Leukocytoclastic vasculitis presenting with Henoch–Schonlein purpura (HSP) was diagnosed according to ACR 1990 criteria and confirmed by skin biopsy. Thirty-seven patients (22 boys, 15 girls) aged 2.5–17 years (9 ± 3.3) were enrolled in the study. Expression of CD95 and apoptosis were investigated by the annexin/PI method on peripheral blood neutrophils and lymphocytes in both the acute and the resolution phases of the disease. The mean neutrophil and lymphocyte CD95 expression was 65.4 ± 37.6% and 33.3 ± 7.3%, respectively, in the acute stage and 62.8 ± 44.2% and 41 ± 20%, respectively, in the resolution (P > 0.05). The percentage of apoptotic peripheral blood neutrophils and lymphocytes as determined by annexin positivity was 13.3 ± 11.31% and 8.6 ± 9.5%, respectively, during the acute phase and 4.6 ± 3.4% and 3.1 ± 3.1%, respectively, in the resolution (P = 0.002, P = 0.008). These results suggest that increased apoptotic process in the immune effector cells in the acute phase of the disease may play an important role in the early control of inflammatory response and repair in leukocytoclastic vasculitis, thereby contributing to the self-limited nature of the disease.

Antineutrophil cytoplasmic antibodies in childhood systemic lupus erythematosus

We aimed to evaluate the presence of peripheral antineutrophil cytoplasmic antibodies (p-ANCA) and cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) in children with SLE and to correlate its association of laboratory findings.Twenty-one children with SLE were studied. Serum samples in patients were tested by indirect immuno-fluorescence (IIF) slide kit (INOVA) for c-ANCA and p-ANCA and by ELISA for myeloperoxidase (MPO-ANCA) and proteinase 3 (PR3-ANCA). All the patients but two were quiescent for lupus at the time of samplingSixteen of 21 patients showed positive IIF staining whereas only 5 had MPO-ANCA and 2 of nine PR3-ANCA.The data suggests that SLE may be associated p-ANCA directed against additional target antigens rather than MPO and may be implicated in the pathogenesis of SLE or may be only non-specific antibodies developed in lupus.

PW01-004 – The sequence analysis in E148Q homozygous patients

Familial Mediterranean fever (FMF) is an autosomal recessive disease associated with a number of mutations of the MEFV gene. To date 246 variants responsible for the disease were identified, one such a variant is E148Q in exon 2. The role of E148Q variant in the development of FMF remains inconclusive. Some authors believe it causes the disease, whereas others favor the concept of a non causative role.

Triple Immunosuppression With Tacrolimus in Pediatric Renal Transplantation: Single-Center Experience

AIM In this single-center cohort, we retrospectively analyzed the efficacy and safety of tacrolimus in pediatric renal transplantation. METHODS We examined the medical records of 22 consecutive renal transplantation recipients (12 boys, 10 girls) receiving tacrolimus, to evaluate occurrence of acute rejection (AR) episodes, glomerular filtration rates (GFR), and side effects. RESULTS The mean recipient age was 15.07 +/- 3.96 years. Seven grafts came from cadaveric, and 15 from living related donors. The patients were placed on immunosuppression with prednisolone and tacrolimus plus azathioprine (n = 8) or mycophenolate mofetil (MMF) (n = 12) or enteric-coated mycophenolate sodium (n = 2). Eighteen patients received basiliximab on days 0 and 4. There were three AR episodes at 5, 9, and 12 months. Mean GFR at the end of 1 and 2 years were 97.1 +/- 24.0 mL/min/1.73 m(2) and 116.9 +/- 42.2 mL/min/1.73 m(2), respectively. There was no graft loss. Hypertension, hyperlipidemia, and hyperglycemia were present in 14 (63.6%), 3 (13.6%), and 3 (13.6%) patients, respectively, without gingival hyperplasia, tremor, or hypertrichosis. Supraventricular tachycardia was noticed in five patients (22.7%), three of whom needed antiarrhythmic drugs (13.6%). CONCLUSION Our single-center experience with tacrolimus, steroid plus azathioprine or MMF or enteric-coated mycophenolate sodium regimen in pediatric kidney recipients showed a low rate of AR with excellent graft survival and function at 1 and 2 year posttransplantation. The increased rate of supraventricular tachycardia in this regimen had not been previously reported; this association merits further studies.

Brown tumour as a complication of secondary hyperparathyroidism in uraemia: A case report

A 15-year-old girl who developed “brown tumour” as a complication of secondary hyperparathyroidism while on maintenance haemodialysis therapy is described. Parathyroidectomy with implantation of a portion of one parathyroid gland was performed. Recovery of the lesion was noted 6 months after surgery and a ratio of about 1/12 was found when the systemic parathormone level was compared to that obtained from the vein draining the implanted parathyroid tissue. We would like to emphasize that signs and symptoms of secondary hyperparathyroidism should be sought for before complications develop; and if medical therapy is unsuccessful, this type of surgery is a justified option.