Dr Irina Buhaescu Dialysis and Renal Transplantation Unit “C. I. Parhon” University Hospital Iasi, Romania	Prof Adrian Covic Full Professor of Nephrology Dialysis and Renal Transplantation Unit “C. I. Parhon” University Hospital Iasi, Romania

 

Introduction

Psoriatic nephropathy is a recently described entity. A Medline search retrieved 17 case reports and one single-case series, all describing different types of glomerular involvement in patients with psoriasis, most frequently mesangial glomerulonephritis with IgA deposits (9 case reports) and membranous nephropathy (6 case reports). In several other cases with nephrotic range proteinuria, usually associating psoriatic arthritis, AA amyloidosis was the underlying pathological finding. (1)

We report the case of a middle-aged man with psoriasis and psoriatic arthropathy, who also developed a nephrotic syndrome, caused by a focal and segmental glomerulosclerosis and leading to end-stage renal disease. This is only the second case of psoriasis-associated FSGS (11), and is therefore interesting as it acts as a reminder to the physician of other rare causes of nephrosis in patients with psoriasis.

Case

A 46 year-old male was referred to the Department of Nephrology, at the ”Dr.C.I.PARHON” University Hospital, Iasi, Romania for evaluation and management of lower limb and palpebral edema.

He had had psoriasis for 15 years, characterized by several remissions and recurrences. Two years after the initial diagnosis, he developed psoriatic arthropathy involving the ankles, wrists, distal interphalangeal and metacarpophalangeal joints. Various treatment strategies had been attempted during this two-year period: topical steroid preparations and ultraviolet therapy for the skin disease and NSAIDs, periodically recommended for the artrhritis flare-up. However, no particular treatment had been administrated over the last 6 months, except for intermittent intra articular cortico- therapy. The patient has no significant family history suggestive of chronic diseases, hypertension and diabetes and no past history of heart or liver diseases.

Ten weeks before the current admission, a routine planned check-up showed normal results. The routine laboratory work-up (including urine analysis and inflammatory status) was normal. During the five weeks that followed, however, he noticed the recurrence of psoriasis disease with flare-up of cutaneous lesions (some of which progressed to become pustular) and arthritis (with total immobility at the tibial and tarsal joints). This was soon followed by edema of the lower limbs and palpebral edema. The patient also declared that he had noticed turbid and foamy urine during these last few weeks.

Clinical examination revealed the presence of several typical cutaneous scaly lesions spread all over the body, with areas of exudates. He had bilateral pitting pedal edema, puffiness of the face and palpebral edema, joint tenderness with limitations of movements at the knee and ankle joints. He was afebrile. Blood pressure was 130/80 mmHg, heart rate – 80/min. Respiratory, cardiovascular, gastrointestinal and neurological systems were normal.

The paraclinical explorations revealed the presence of heavy proteinuria 8g/day, microscopic hematuria and normal renal function (creatinine 106 m mol/l), hypoproteinemia 44,7 g/l with hypoalbuminemia 24,5 g/l, hyper a 1 2,4 g/l and hyper a 2 globulinemia 10g/l, hypogammaglobulinemia 7,7 g/l. Cholesterol levels were elevated at 15.2 mmol/l, as well as triglyceride levels at 3.2 mmol/l. Liver function tests were normal. An associated inflammatory syndrome was detected: CRP 48 mg%, ESR 78 mm/hour, hyperleucocytosis 14800/mmc, fibrinogen 567 mg%, inflammatory anemia Hb 10g%, Ht 34 %, with hyposiderinemia 35 g % and elevated ferritin levels of 946 µg/l.

The only abnormality in the immunological profile consisted of an increased serum Ig A titer at 677 mg%. The ANCA antibodies, the serum complement and the rheumatoid factor values were within normal limits. Circulating immune complexes were absent. Viral serologies for HIV, hepatitis B and C and parvovirus were negative.

A renal biopsy was performed. On light microscopy (figure 1a) a focal and segmental glomerulosclerosis was described, with collapsed capillary lumina in the affected segments and acellular hyaline subendothelial deposits, tubular atrophy and interstitial inflammatory infiltrates. Immunofluorescent microscopy (figure 1b) demonstrated IgM, C3 and C1q deposits in the segmental lesions.

 

Figure 1 Renal biopsy in a case of nephrotic syndrome and psoriasis
Figure 1a	Figure 1b

The following management plan was prescribed: dietary modifications, a 3-day course of methylprednisolone 500 mg, followed by prednisone 1mg/kg/day, enalapril 10mg/day, atorvostatin 10mg/day, aspirin 100 mg/day, dipyridamole 225 mg/day. Four weeks after the initiation of this treatment, he presented with persistent edema, proteinuria of 9.4g/day, hypoproteinemia of 44.7g/l with hypoalbuminemia of 18g/l, severe dyslipidemia (S. Cholesterol = 17 mmol/l, triglycerides = 3,6 mmol/l) and altered renal function (creatinine 159 m mol/l). A second course of methylprednisolone 3 x 1 g/day was prescribed, followed by cyclophosphamide 0,75 mg/m2 intravenously. The ACE inhibitor and the statin dose was increased to a maximal level and the patient was referred to his general practitioner and to his local nephrology unit.

Subsequently, he received a 6-month course of pathogenic treatment (prednisone and monthly cyclophosphamide pulses) but, in spite of this, the proteinuria remained high (>6 g/day) and renal function deteriorated gradually. 15 months after the initial presentation with nephrotic syndrome he required renal replacement therapy with intermittent hemodialysis. The evolution of the patient's disease and treatment is presented in figure 2.

Figure 2 - The evolution of patient's disease and treatment is presented.

Discussion

The occurrence of glomerular diseases in patients affected by psoriasis is rare, although the number of reports has been increasing over recent years. Three major patterns are evident.

The mesangial nephropathy with IgA deposits , usually presenting with sub-nephrotic proteinuria, is the most frequent glomerulonephritis reported in association with psoriasis. An elevated IgA serum level seems to be characteristic (3,4). The pathogenesis of psoriasis vulgaris and IgA nephropathy may be related through an immune mechanism (5). Disregulation of the IgA system, leading to elevated serum IgA or IgA-containing immune complexes, or an intrinsic defect in the structure of IgA, leading to its deposition in the mesangium, may be present in psoriasis (11).

Secondly, a long-standing history of psoriasis and psoriatic arthritis is associated with secondary AA amyloidosis and nephrotic syndrome. This pattern was recently reviewed by Kagan (1) and also accounted for the majority of cases in the single-case series reported by Varshavski (2), where 59% of these patients had renal failure at presentation, and 56% died shortly after diagnosis, supporting the view that amyloidosis associated with psoriasis is an aggressive disease that can be fatal (1), although there are sporadic cases with a favorable evolution under colchicine (1) or infliximab, a monoclonal antibody anti-TNF alpha (12).

Finally, an equally frequent presentation is the membranous glomerulonephritis , considered to be, in the majority of cases, drug-related (NSAIDs, gold salts) (7, 8). The association of the mesangiocapillary glomerulonephritis and the minimal change disease has been rarely described (9, 10).

Author for Correspondence:

Adrian Covic MD PhD

Professor of Nephrology

Parhon University Hospital

50 Carol 1 st Blvd.

Iasi 6600, Romania

Tel: ++40-721-280246

Fax: ++40-232-210940

Email: acovic@xnet.ro