Transfus. Sci. 1992; 13:119-123 09553886/92 $5.00+0.00 Printed in Great Britain. All rights reserved Copyright @J 1992 Pergamon Press plc

Plasma Exchange in Rheumatoid Vasculitis

Rui Clemente Coelho Miguel Lea1 Galvgo

n Rheumatoid vasculitis (RV) is a rare but severe complication of rheumatoid arthritis, affecting skin, nerves and inter- nal organs; it is usually treated with immunosuppressive drugs. Plasma exchange (PE) was combined with methylprednisolone and cyclophospha- mide in 3 women with RV. Stabilization of peripheral necrotic lesions was accom- plished in all patients and the one suffer- ing from Mononeuritis Multiplex had a moderate improvement. We reviewed the literature on diagnosis and treatment of RV and found 30 patients reported as treated with PE alone or in combined therapy; according to classifiable data (28 cases), we concluded that PE is particu- larly suitable to patients unable to undergo immunosuppression or with life-threatening forms of RV. n

INTRODUCTION

119

Plasma exchange (PE) has been accepted as a good treatment modality in well defined clinical situations: hypervisco- sity syndrome, thrombotic thrombocy- topenic purpura, myasthenia gravis, cres- centic glomerulonephritis with renal insufficiency, Goodpasture’s syndrome, familial hypercholesterolemia, l and acute Guillain-Barre syndrome.2 In some

hmuno-Haemotherapy Department, Hospital de Santa Maria, Av. Prof. Egas Moniz, Lisbon, Portugal. Received 6/91; Accepted 8/91.

other selected conditions,’ patients may benefit from PE: these include rheuma- toid vasculitis (RV), a severe complica- tion of classical rheumatoid arthritis ( RA),3, 4 which is usually associated with

significant morbidity (cutaneous iecrosis5 and polyneuropathy6 and a high mortality rate (30%).‘, ’ The theoretical basis for PE treatment in autoimmune disorders is to remove immune com- plexes and inflammatory mediators from blood, with subsequent microcirculation clearance9 and dessaturation of the mononuclear-phagocytic system; lo, I’ PE must be combined with immunosup- pressive therapy in order to down- regulate self-reacting lymphocyte clones. This paper describes 3 patients with RV treated with PE plus methyl- prednisolone (MP) and cyclophospha- mide (CPP) and reviews 25 of the 30 cases reported in the literature managed by pE 9, 12-19

MATERIALS AND METHODS

There are 30 RV patients reported in the literature, whose therapy included PE. We will analyze those cases with classi- fiable data (25) and our 3 patients, which we describe here:

Case No. 1

A 65yr-old woman had nodular RA for 14 yr. In January 1983 she was admitted to hospital because she developed digital necrosis, purporic lesions on feet and

120 Transfus. Sci. Vol. 13. No. 1

mononeuritis multiplex (MM) on lower limbs. Daily immunosuppressive ther- apy ( 100 mg MP plus 50 mg CPP) was immediately started and after a week the patient was enrolled in a PE program: five sessions of I.3 plasma volume exchange were performed in 20 days, using fresh frozen plasma as replacing solution. A clear delimitation of necrotic areas and a neurologic improvement occurred in 3 weeks.

Case No. 2

A 75 yr-old woman was diagnosed of RA in April 1986; since then the disease had been erosive, with strongly positive serology. In November 1986 ischaemic lesions appeared on hands and feet, and evolved quickly to distal necrosis on 8 fingers. She was given immunosuppres- sive therapy (100 mg MP plus 100 mg CPP) and submitted to seven sessions of 1.3 plasma volume exchange (4% albu- min) in 17 days. The stabilization of the necrotic border and the remission of purpuric nodules, led to discontinuing of PE.

Case No. 3

A 63 yr-old woman had had deforming and erosive RA for 13 yr, being poorly controlled with corticosteroids. In Octo- ber 1987 she noticed mild signs of cuta- neous vasculitis on her right foot, which progressed rapidly to necrosis of one finger. Combined therapy of PE and daily immunosuppressive drugs (60 mg MP plus 150 mg CPP) was instituted. The apheresis protocol was performed on 13 days: six sessions of 0.9 plasma volume exchange using 4% albumin as replacing solution. Ischaemic and trophic changes were controlled after 2 weeks treatment, avoiding subsequent amputation. Erythrocyte sedimentation rate, C- reactive Protein and rheumatoid factor, all became normal.

The method we used to evaluate literature reports was to review all patients with respect to the following

criteria: RA characterization, presenta- tion of indications for PE, frequency and associated therapy, laboratory monitor- ing and clinical results.

RESULTS

RA Characterization

Classical RA manifestations in patients developing systemic vasculitis were pre- sent in most patients: long disease dura- tion (17.5 yr), severe articular damage (69% ), occurrence of rheumatoid nodules (65%) and strongly positive serology (73%) (Table 1).

Presentation of RV

The most common clinical features observed were: gangrene extremity (64%), skin ulcers (57%)‘ polyneuro- pathy (50%) and purpuric nodules (3 1%) (Table 2).

PE Indications

15 were treated with PE for intractable disease, 3 for corticosteroid resistance, 2 for cryoglobulinemia and one for marrow depression secondary to cyclophospha- mide.

PE Schedule

Scott, Duquesnoy, Bjelle and Coelho followed a PE schedule consisting in a short-term intensive program followed by a maintenance protocol, only varying in the plasma volume exchanged. Roux and Goldman group varied PE method among patients, and some also received several treatments in the first week.

Associated Therapy

According to reported data, 15 patients were medicated with MP plus CPP, 5 with MP alone, 3 with CPP alone and 2 with azathioprine. Three groups describe 5 patients managed by PE without associ- ated therapy.

PE in Rheumatoid Vasculitis 121

Table 1. Rheumatoid Arthritis: Clinical Features

9 12 13 14 15 16 * Total

Articular damage 2/2 ND ND ND II2 416 213 9113 (69%) Rheumatoid nodules ND 3/4 819 II2 212 216 l/3 17/26 (65%) Strongly positive ND 4/4 ND 212 l/2 II2 l/3 11/E (73%)

n/n = patients affected/patients reported per parameter. ND = non determined.

Table 2. Forms of Presentation of Rheumatoid Vasculitis

Gangrene of extremities PolvneuroDathv

9 12 13

II2 314 619 l/2 314 619

14

l/2 II2

15 16

212 316 o/2 216

l Total

213 18128 (64%) l/3 14/28 (SO%]

Pu&oric ioduies O/2 ND ND o/2 l/2 216 II3 4/13 (31%) Skin ulcers l/2 214 619 212 l/2 l/6 313 16128 (57%)

n/n = patients affected/patients reported per parameter. ND = non determined.

Laboratory Monitoring

No special laboratory parameters were used to monitor respopnse to PE proce- dures: erythrocyte sedimentation rate was mentioned by 5 groups, rheumatoid factor by six, complement consumption by three and immune complexes by two.

Clinical Response

Most authors were not very explicit about clinical evaluation after the PE program was started, but an accurate evaluation of available data shows that 55% of patients improved, 36% achieved stabilization, 23% had no response and 14% died (Table 3).

DISCUSSION

Vasculitic syndromes have been difficult to classify,20, 21 both from a clinical and histological point of view. Bacon’ includes RV in systemic necrotizing arteritis, where medium-size and small

Table 3. Clinical Response

arteries are major targets of inflamma- tory process; however venules and capil- laries may also be involved in milder forms of disease.22 Schneider et ~1.~ divides RV in two subtypes: type I, which includes mononeuritis multiplex and gangrene and type II which includes all other manifestations of RV. Most authors describe it as a rare complication of long-lasting RA, 23, 24 affecting patients with rheumatoid nodules25 and strongly positive serology. 26 The underlying phy- siopathological mechanism consists in immune complex deposition in the microcirculation,27, 28 leading to activa- tion of neutrophils,29 platelets,30 macrophages31 and T-lymphocytes.’ The final deleterious event in tissues is prob- ably related to free oxygen radicals and tumor necrosis factor-a (TNF-a).

The management of RV is contro- versia14, ’ as with many autoimmune disorders. Scott and Bacon32 treated 100 patients with intermittent boluses of MP plus CPP and concluded this drug reg- imen led to healing and lowered relapse

9 12 13 14 15 16 l Total

Improvement 212 719 Stabilization Ab response 214 2l9 Death 2l4

n/n = patients evaluated/patients reported per group.

l/2 l/6 l/3 12l22 (55%) 212 l/2 316 213 8l22 (36%)

l/6 5/22 (23%) II6 3/22 (14%)

122 Transfus. Sci. Vol. 13, No. 1

and mortality rates (in agreement with former results by Fauci et ~1.~~ and Abel et ~1.~~). Schneider et ~1.~ states that aggressive therapy should be reserved for life-threatening situations like gangrene, mononeuritis multiplex, renal failure and polyserositis. Milder RV forms can be treated more conservatively as they tend to respond well to conventional therapy.35

The group of Goldman12 was the first to introduce PE in the management of RV (1979); carried out an empirical basis on that occasion, its role is still not totally clarified. No randomized controlled study with PE alone has been reported, and only occasional cases have been reported. 9, 17, 28, 31 A total of 8 patients have been described and all except one improved or achieved clinical stabiliza- tion. Our patients, treated with com- bined therapy, obtained a relatively good outcome, confirming previous reports.

This literature review does not per- mit any clear-cut conclusions as no stan- dard procedures were followed by the various groups. Our personal view about RV is that PE should be reserved for patients who cannot undergo immuno- suppressive therapy (namely corticoster- oids), those affected by very severe condi- tions (gangrene and/or mononeuritis multiplex) and for cases complicated by cryoglobulinemia.

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