Costello syndrome-associated orthopaedic manifestations focussed on kyphoscoliosis: a case series describing the natural course.

Costello syndrome (CS) is a rare genetic condition caused by a heterozygous mutation in the HRAS gene, with an estimated prevalence of 1: 300 000. Individuals with CS present with characteristic features including scoliosis, kyphosis, Chiari 1 malformation, and syringomyelia. The natural history of the spinal deformity associated with CS has been incompletely described. This case series describes the spinal deformity associated with CS and sets out a strategy for screening and treatment. The clinical records and spinal radiographs of nine consecutive CS patients encountered at a single centre were reviewed. Radiological assessments for the presence and progression of scoliosis were studied. Nine patients with confirmed CS were followed for a mean of 6.6 years. Five patients showed mild scoliosis. Two patients had lumbar kyphosis in addition to their scoliosis, and one showed scoliosis with proximal thoracic kyphosis. Three patients underwent investigation with MRI, one of which showed Chiari I malformation and a syrinx. One showed no change in the severity of their deformity over time. The remaining four patients showed a rate of increasing coronal deformity of 2.1° per year. There were no cases of rapid progression. All cases showed delayed skeletal maturity. The spinal deformity in CS appears to be slowly progressive. To identify those at risk of more rapid progression, brain and spine MRI should be carried out to exclude structural neurological abnormalities. Long follow-up is required for patients with spinal deformity in CS due to the delay in reaching skeletal maturity. Evidence level: 4.

A Case Demonstrating the Pathological Relationship between Granulomatous Vasculitis and Glomerular Lesion in Renal Sarcoidosis.

We experienced a rare case of tubulointerstitial angiocentric granulomatous vasculitis with focal segmental glomerulosclerosis (FSGS) and associated sarcoidosis. Our patient was an 18-year-old man who presented with exertional cough and dyspnea. He also had overt proteinuria (3.0 g/24 h), normal renal function (eGFR 95 mL/min/1.73 m2), heart failure, and hypertension. He had no previous episode of hypertension. These manifestations immediately improved after the administration of antihypertensive therapy that contained an angiotensin-converting enzyme inhibitor, calcium antagonists, beta antagonists, and diuretics. However, he, later on, developed renal dysfunction, with worsening of both proteinuria and hypertension. Renal biopsy was performed and showed epithelioid cells that were arranged concentrically around small blood vessels in tubulointerstitial granulomas. In the glomeruli, the segmental sclerotic lesions were classified as a perihilar variant of FSGS. There were no inflammatory changes, such as a mesangial lesion, inflammatory cell infiltration, fibrinoid necrosis, or crescent formation, and no glomerular granuloma. In the tubulointerstitial granulomas, the intimal elastic lamina of the interlobular arteries was reduplicated, and the intimal wall thickness of renal arterioles was remarkable. After receiving oral prednisolone therapy, the overt proteinuria resolved, the eGFR recovered from 39.4 to 60.6 mL/min/1.73 m2, and hypertension was managed more easily. Thereafter, he did not experience any recurrence. The concurrent improvement of renal function and proteinuria by steroid treatment suggested a relationship between the glomerular lesions and the tubulointerstitial granulomatous vasculitis with associated sarcoidosis.

Clinical characteristics of biopsy-proven renal sarcoidosis in Japan.

Background: Although some articles have described renal sarcoidosis, the incidence among biopsy cases remains unclear. Here, we defined the incidence of renal sarcoidosis among renal biopsy cases and analyzed the clinical course. Methods: We performed an epidemiological study examining renal biopsy cases treated at 5 centers between January 2000 and September 2015 and identified 16 cases (7 men, 9 women; mean (±SD) age, 59.4±18.6 years) out of a total of 14191 renal biopsy cases. Renal involvement of sarcoidosis was defined as granulomatous tubulointerstitial nephritis, tubulointerstitial nephritis without granulomatous lesions, and renal calcinosis. Fifteen of the cases were treated with steroid therapy. One case initially received steroid pulse therapy. The outcome was evaluated based on the estimated glomerular filtration rate (eGFR), CKD stage, and the change in eGFR (ΔeGFR) after treatment. A favorable response was defined as ΔeGFR ≥25%. Results: The incidence of renal sarcoidosis was 0.11%. The mean eGFR was 28.2±16.1 mL/min/1.73 m2. At the last observation, the mean eGFR was 43.7±19.7 mL/min/1.73 m2. Although a favorable response to steroid therapy was found in the majority of cases (10/15, 67%), 12 of the 15 cases (80%) had residual renal dysfunction at the last observation and 8 cases (53%) had moderate to severe renal dysfunction. Conclusion: Renal sarcoidosis is extremely rare among renal biopsy cases. Among cases with an unfavorable response to steroid therapy, pathogenetic mechanisms other than sarcoidosis and severe nephron damage were observed. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 252-260).