Efficacy of anakinra in a patient with systemic amyloidosis presenting as amyloidoma

Amyloidosis is a heterogeneous group of disorders characterized by extracellular deposition of unique protein fibrils. The least common presentation of an amyloid deposition is as a discrete mass called amyloidoma or amyloid tumor. We report a case of a soft tissue amyloidoma in the abdomen of a 16‐year‐old girl who was diagnosed as having systemic amyloidosis. A girl aged 16 years was referred to our hospital with a pre‐diagnosis of a retroperitoneal mass documented with abdominal ultrasonography and tomography. A laboratory examination revealed nephrotic syndrome. She underwent surgery for a complete resection of the lesion. A histopathologic examination with Congo red and crystal violet dyes verified the diagnosis of amyloidoma. An immunohistochemical study for amyloid A protein was positive. A renal biopsy was also compatible with AA amyloidosis. A detailed search for the etiology of systemic amyloidosis revealed heterozygous mutation in the Mediterranean fever gene. Treatment with colchicine and anakinra were started with the diagnosis of familial Mediterranean fever because the other causes of secondary amyloidosis were ruled out. After 3 months of anakinra treatment, the laboratory findings returned to normal and excessive proteinuria disappeared. In countries where FMF and other autoinflammatory diseases are prevelant, systemic amyloidosis should be kept in mind in the differential diagnosis of children who present with nephrotic syndrome and abdominal mass. Taking previously reported cases and our case together, it appears that anti‐interleukin‐1 treatment represents a promising new approach in a subset of patients with systemic amyloidosis secondary to autoinflammatory diseases.     

Cortical spreading depression can be triggered by sensory stimulation in primed wild type mouse brain: a mechanistic insight to migraine aura generation

BackgroundUnlike the spontaneously appearing aura in migraineurs, experimentally, cortical spreading depression (CSD), the neurophysiological correlate of aura is induced by non-physiological stimuli. Consequently, neural mechanisms involved in spontaneous CSD generation, which may provide insight into how migraine starts in an otherwise healthy brain, remain largely unclear. We hypothesized that CSD can be physiologically induced by sensory stimulation in primed mouse brain.MethodsCortex was made susceptible to CSD with partial inhibition of Na⁺/K⁺-ATPase by epidural application of a low concentration of Na⁺/K⁺-ATPase blocker ouabain, allowing longer than 30-min intervals between CSDs or by knocking-down α2 subunit of Na⁺/K⁺-ATPase, which is crucial for K⁺ and glutamate re-uptake, with shRNA. Stimulation-triggered CSDs and extracellular K⁺ changes were monitored in vivo electrophysiologically and a K⁺-sensitive fluoroprobe (IPG-4), respectively.ResultsAfter priming with ouabain, photic stimulation significantly increased the CSD incidence compared with non-stimulated animals (44.0 vs. 4.9%, p < 0.001). Whisker stimulation also significantly increased the CSD incidence, albeit less effectively (14.9 vs. 2.4%, p = 0.02). Knocking-down Na⁺/K⁺-ATPase (50% decrease in mRNA) lowered the CSD threshold in all mice tested with KCl but triggered CSDs in 14.3% and 16.7% of mice with photic and whisker stimulation, respectively. Confirming Na⁺/K⁺-ATPase hypofunction, extracellular K⁺ significantly rose during sensory stimulation after ouabain or shRNA treatment unlike controls. In line with the higher CSD susceptibility observed, K⁺ rise was more prominent after ouabain. To gain insight to preventive mechanisms reducing the probability of stimulus-evoked CSDs, we applied an A1-receptor antagonist (DPCPX) to the occipital cortex, because adenosine formed during stimulation from ATP can reduce CSD susceptibility. DPCPX induced spontaneous CSDs but only small-DC shifts along with suppression of EEG spikes during photic stimulation, suggesting that the inhibition co-activated with sensory stimulation could limit CSD ignition when K⁺ uptake was not sufficiently suppressed as with ouabain.ConclusionsNormal brain is well protected against CSD generation. For CSD to be ignited under physiological conditions, priming and predisposing factors are required as seen in migraine patients. Intense sensory stimulation has potential to trigger CSD when co-existing conditions bring extracellular K⁺ and glutamate concentrations over CSD-ignition threshold and stimulation-evoked inhibitory mechanisms are overcome.     

Dermatoses in overweight and obese children and their relationship with insulin and skin color

Background/Aim

The aim of the present study was to investigate the prevalence of obesity-related dermatoses in obese children, and the association between these dermatoses and insulin resistance as well as skin color.

Methods

Obese, overweight, and normal weight children according to body mass index who were followed up and treated in the outpatient clinics were included in the study. Dermatological examinations of the participants were performed, and fasting insulin and glucose levels were checked.

Results

The obese and overweight children were evaluated as the patient group (70 girls, 41 boys, mean age: 12.37 ± 3.14 years). One hundred one healthy children with normal weight were determined as the control group (59 girls, 42 boys, mean age: 12.15 ± 2.43). The first five common dermatoses in the patient group when compared with the control group were keratosis pilaris (KP), striae distensae, hyperhidrosis, acanthosis nigricans (AN), and plantar hyperkeratosis. The first five dermatoses which were positively correlated with formation and insulin resistance were KP, striae distensae, AN, hyperhidrosis, and plantar hyperkeratosis. According to the Fitzpatrick skin scale, we found that the darker the skin color, the higher the probability of AN and KP (OR, 0.298; 95% CI, 0.106–0.834, p = 0.021; OR, 0.306; 95% CI, 0.117–0.796, p = 0.015, respectively).

Conclusion

Some dermatoses associated with obesity and insulin resistance were not found in obese children, or there was no significant association. These results indicate that many skin morbidities may be prevented by preventing and treating obesity and insulin resistance in the early period.     

Clinical features of generalized lipodystrophy in Turkey: A cohort analysis

Aim

To describe the Turkish generalized lipodystrophy (GL) cohort with the frequency of each complication and the death rate during the period of the follow-up.

Methods

This study reports on 72 patients with GL (47 families) registered at different centres in Turkey that cover all regions of the country. The mean ± SD follow-up was 86 ± 78 months.

Results

The Kaplan–Meier estimate of the median time to diagnosis of diabetes and/or prediabetes was 16 years. Hyperglycaemia was not controlled in 37 of 45 patients (82.2%) with diabetes. Hypertriglyceridaemia developed in 65 patients (90.3%). The Kaplan–Meier estimate of the median time to diagnosis of hypertriglyceridaemia was 14 years. Hypertriglyceridaemia was severe (≥ 500 mg/dl) in 38 patients (52.8%). Seven (9.7%) patients suffered from pancreatitis. The Kaplan–Meier estimate of the median time to diagnosis of hepatic steatosis was 15 years. Liver disease progressed to cirrhosis in nine patients (12.5%). Liver disease was more severe in congenital lipodystrophy type 2 (CGL2). Proteinuric chronic kidney disease (CKD) developed in 32 patients (44.4%) and cardiac disease in 23 patients (31.9%). Kaplan–Meier estimates of the median time to diagnosis of CKD and cardiac disease were 25 and 45 years, respectively. Females appeared to have a more severe metabolic disease, with an earlier onset of metabolic abnormalities. Ten patients died during the follow-up period. Causes of death were end-stage renal disease, sepsis (because of recurrent intestinal perforations, coronavirus disease, diabetic foot infection and following coronary artery bypass graft surgery), myocardial infarction, heart failure because of dilated cardiomyopathy, stroke, liver complications and angiosarcoma.

Conclusions

Standard treatment approaches have only a limited impact and do not prevent the development of severe metabolic abnormalities and early onset of organ complications in GL.     

Dense genome‐wide linkage analysis of rheumatoid arthritis,including covariates

Objective

Rheumatoid arthritis (RA) is a heterogeneous disease that exhibits a complex genetic component. Previous RA genome scans confirmed the involvement of the HLA region and generated data on suggestive signals at non‐HLA regions, albeit with few overlaps in findings between studies. The present study was undertaken to detect potential RA gene regions and to estimate the number of true RA gene regions, taking into account the heterogeneity of RA, through performance of a dense genome scan.

Methods

In a study of 88 French Caucasian families (105 RA sibpairs), 1,088 microsatellite markers were genotyped (3.3‐cM genome scan), and a multipoint model‐free linkage analysis was performed. The statistical assessment of the results relied on 10,000 computer simulations. A covariate‐based multipoint model‐free linkage analysis was performed on the locations of regions with suggestive evidence for linkage.

Results

Involvement of the HLA region was strongly confirmed (P = 6 × 10⁻⁵), and 19 non‐HLA regions showed suggestive evidence for linkage (P < 0.05); 9 of these overlapped with regions suggested in other published RA genome scans. A routine 12‐cM genome scan with the same families would have detected only 7 of the 19 regions, including only 4 of the 9 overlapping regions. From the 10,000 computer simulations, we estimated that 8 ± 4 regions (mean ± SD) were true‐positives. RA covariate–based analysis provided additional linkage evidence for 3 regions, with age at disease onset, erosions, and HLA–DRB1 shared epitope as covariates.

Conclusion

The results of this study provide evidence of 19 non‐HLA RA gene regions, with an estimate of 8 ± 4 as true‐positives, and provide additional evidence for 3 regions from covariate‐based analysis.