A 54-year-old patient was admitted for fever, diarrhea, and acute renal failure.
He had no significant medical history, did not take any medication, and had not traveled recently.
He had no relevant familial history.
Fifteen days before his admission, he developed fever, fluctuant rash, diarrhea, and pain in the joints.
On admission, blood pressure was 140/70 mm Hg, temperature 39°C.
Physical examination showed severe edema involving both lower and upper limbs, as well as ascites and pleural effusion.
Cervical and axillar infracentimetric lymphadenopathies were present, together with hepatosplenomegaly, confirmed by computed tomography (CT) scan.
Bilateral arthritis of the ankles resolved spontaneously.
Blood analysis revealed (Table ​(Table1):1): leukocytosis, normal hemoglobin and platelet levels with no biologic sign of hemolysis, elevated C-reactive protein, low albumin, elevated serum creatinin, mild proteinuria and no hematuria.
Despite intravenous rehydration using saline and albumin, renal function worsened and the patient required dialysis.
While diagnostic investigations were performed, hemiplegia occurred: brain MRI showed multifocal ischemic lesions.
Echographic and rythmologic studies ruled out any cardiologic cause for the stroke.
A renal biopsy was performed (Fig.1A and B).
Periodic acid–Schiff (PAS) staining showed endotheliosis in all glomeruli (Fig.1A, arrows), associated with mesangiolysis and double contours on silver staining (Fig.1B, arrows), and no arteriolar thrombus.
A moderate CD20+ B lymphocyte infiltrate was present in the interstitium, with a peritubularcapillaritis.
Immunofluorescence study did not show any deposit.
Lymph node biopsy (Fig.2A and B) showed abnormal follicles with hyalinization of germinal center, and an onion-skin aspect of the mantle zone.
Clinical presentation and lymph node histology were consistent with hyaline-vascular multicentric Castleman disease (MCD).
HIV and HHV-8 serology, as well as HHV-8 lymph node tissue staining, were negative.
Serum vascular endothelium growth factor (VEGF) was highly elevated.
There was no biologic manifestation of thrombotic microangiopathy (TMA), but the renal biopsy and brain MRI were consistent with glomerular and neurologic TMA lesions.
No other apparent cause of thrombotic microvascular involvement was noted.
Notably, there was no evidence for infection with shiga toxin-producing germs, ADAMTS-13 activity was decreased up to 14% but remained above 5%, and the alternative complement pathway was normal.
Plasma exchange was initiated due to the kidney histological lesions and the multifocal ischemic brain lesions.
It was discontinued after 1 month after the onset of the disease, since the patient's condition remained stable.
Furthermore, chemotherapy including 6 courses of rituximab (375 mg/m2), cyclophosphamide (750 mg/m2), and dexamethasone (40 mg/day from day 1 to day 4) was started together with plasma exchanges (chemotherapy was performed immediately after plasma exchanges).
Courses were performed every 3 weeks.
Clinical manifestations of vascular leak syndrome regressed, renal function normalized, and serum VEGF level decreased to 825 pg/mL after 1 course of chemotherapy.
The patient was discharged 43 days after admission.
No neurological event occurred after initiating the treatment.
Thoraco-abdominal CT scan was performed after 6 courses of chemotherapy, showing a normal liver and spleen size and no lymph node enlargement.
One year after the diagnosis, remission of MCD is persistent and plasma creatinine is 86 μmol/L, with no proteinuria.