Prof Judit Nagy Second Department of Medicine and Nephrological Center Pecs University, Faculty of Medicine Pecs, Hungary

 

A 30-year old Caucasian man, a violinist, was seen by his GP on December 2001 because of an upper respiratory tract infection with fever (body temperature 39.5°C) and with periumbilical pain. After a short symptomatic treatment he felt better. 2 weeks later, on January 2002 during a transatlantic flight he was found to have a purpuric rash and a moderate symmetrical oedema on his legs. After arriving he was referred to an outpatient department in the USA where they found minimal proteinuria, normal blood cell count, normal renal function and excluded deep vein thrombosis by Doppler ultrasound. They suspected vasculitis.

QUESTION 1

ANCA, ds-DNA, HCV, HBV, HIV serology was negative. After 3 days bed rest he continued his tour with his troop.
4 days later he was admitted to St. Luke Hospital, Jacksonville, FL, because of a severe generalised oedema, palpable purpuric rash on both legs and acute renal failure. Urinanalysis showed proteinuria (4.5 g/day) with irrelevant urinary sediments with low S-albumin (24.6 g/l). S-creatinin was 247 µmol/l, BUN: 20.1 mmol/l. He had a long history of cigarette smoking, pollen allergy and Penicillin hypersensitivity.
He was referred to a nephrologist who (after exclusion of postrenal acute renal failure by renal ultrasonography) indicated a renal biopsy. The pathological picture showed severe diffuse and global mesangial cell proliferation, focal segmental fibrinoid necrosis in the glomeruli by light microscopy and 3+ granular mesangial staining with IgA and 1+ staining with C3 by immunohistology. C1q and C4 were negative.

QUESTION 2 AND 3

Henoch-Schönlein purpura was diagnosed with nephrotic syndrome. He was put on three days of high dose Solu-Medrol 1 gram per day and then titrated down to prednisolon 60 mg daily . He was recommended to continue long-term prednisolon therapy. After 5 days he came back to Hungary. He was on prednisolon treatment for 1 week but because of the severe generalised oedema he was referred to our Nephrological Center.
In February 2002 he was admitted with severe nephrotic syndrome with generalised oedema, proteinuria (6.4 g/day), haematuria (50-90 dysmorphic red blood cells per high-power field). His blood pressure was normal. S-creatinine: 281 µmol/l, creatinin clearance 48 ml/min. S-IgA 4.2 g/l, S-cholesterol 12.1 mmol/l, S-tryglicerid 3.63 mmol/l. Protein, calorie and salt-restricted diet, ACEI, statin combined diuretic and methylprednisolon treatment 60 mg for further 6 weeks was moderately effective, albumin infusions with Furosemide further decreased his generalised oedema. He became oedema-free after 6-week treatment, proteinuria decreased to 0.5-1.0 g/day. His methylprednisolon was slowly titrated down. But, because of no change in haematuria and in renal function and moderate but permanent proteinuria we repeated the renal biopsy.

Figure 1. Moderate to marked mesangial matrix expansion can be seen in this glomerulus (PAS, x200).

Figure 2. The glomerulus shows moderate to severe sclerosis with fibrous crescent (PAS, x200).

Figure 3. Glomerular deposits of IgA show a global homogenous and granular mesangial pattern by immunohistology (x400).

Figure 4. In addition to mesangial deposits, granular deposits are seen in the GBM (x400).

Figure 5. Electron micrograph: glomerular capillary loop with numerous subepithelial and intramembranous electron-dense deposits.

QUESTION 4

Figure 6. Electon micrograph of a portion of a glomerulus showing a great increase in the mesangial matrix and thickening of the basement membrane.

Figure 7. This electron micrograph shows microtubular and fibrillary deposits in the subendothelial layer of the basement membrane.

QUESTION 5

There was no amyloid deposition in the renal biopsy by congo red staining. Oral glucose tolerance test (OGTT) showed impaired glucose tolerance (IGT). There was no cryoglobulin in the circulation.
Further treatment was based on the clinical picture (mild proteinuria, slightly elevated blood pressure, obesity, IGT, hyperlipidaemia, smoking, moderately decreased renal function) and on the renal biopsy findings (diabetic and sclerotic lesions in the glomeruli, interstitial fibrosis with round cell infiltration). Diet (protein, calorie, salt restricted, native sugar free), moderate regular exercise, stop smoking, ACEI, pentoxyphilline, statins.
At last check–up (Sept. 2003) he had no complaints, oedema-free, blood pressure was normal (120/75 mmHg), blood-sugar 4.48 mmol/l, OGTT negative, S-creatinine 96 µmol/l, S-cholesterol 4.17 mmol/l, S-tryglicerid 1.15 mmol/l, S-albumin 41.9 g/l, had miled proteinuria (albuminuria: 150 mg/day), haematuria 5-8 red blood cells/high power field.
Summarizing the case: a severe Henoch-Schönlein syndrome with secondary (?) diabetes "healed" with chronic glomerular and tubulointerstitial histological damage and with mild alterations in laboratory examinations.

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