Plasma exchange in rheumatoid vasculitis

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Transfus. Sci. 1992; 13:119-123 Printed in Great Britain. All rights reserved

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 internal organs; it is usually treated with Plasma immunosuppressive drugs. exchange (PE) was combined with methylprednisolone and cyclophosphamide in 3 women with RV. Stabilization of peripheral necrotic lesions was accomplished in all patients and the one suffering 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 particularly suitable to patients unable to undergo immunosuppression or with life-threatening forms of RV. n

other selected conditions,’ patients may benefit from PE: these include rheumatoid vasculitis (RV), a severe complication 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 complexes and inflammatory mediators from blood, with subsequent microcirculation and dessaturation of the clearance9 mononuclear-phagocytic system; lo,I’ PE must be combined with immunosuppressive therapy in order to downself-reacting regulate lymphocyte clones. This paper describes 3 patients with RV treated with PE plus methylprednisolone (MP) and cyclophosphamide (CPP) and reviews 25 of the 30 cases reported in the literature managed by pE

9, 12-19

INTRODUCTION MATERIALS AND METHODS

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

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

There are 30 RV patients reported in the literature, whose therapy included PE. We will analyze those cases with classifiable 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

de Santa

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mononeuritis multiplex (MM) on lower limbs. Daily immunosuppressive therapy ( 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 immunosuppressive therapy (100 mg MP plus 100 mg CPP) and submitted to seven sessions of 1.3 plasma volume exchange (4% albumin) 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 October 1987 she noticed mild signs of cutaneous 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 amputation. subsequent Erythrocyte sedimentation rate, Creactive 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, presentation of indications for PE, frequency and associated therapy, laboratory monitoring and clinical results.

RESULTS RA Characterization Classical RA manifestations in patients developing systemic vasculitis were present in most patients: long disease duration (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%)‘ polyneuropathy (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 cyclophosphamide. 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 associated therapy.

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PE in Rheumatoid Vasculitis

Table 1.

Rheumatoid

Arthritis:

9 Articular damage Rheumatoid nodules Strongly positive n/n = ND =

2/2 ND ND

ND 3/4 4/4

ND 819 ND

Forms of Presentation

Gangrene of extremities PolvneuroDathv Pu&oric ioduies Skin ulcers

15

16

*

Total

ND II2 212

II2 212 l/2

416 216 II2

213 l/3 l/3

9113 (69%) 17/26 (65%) 11/E (73%)

of Rheumatoid

Total

Vasculitis

9

12

13

14

15

16

l

II2 l/2 O/2 l/2

314 314 ND 214

619 619 ND 619

l/2 II2 o/2 212

212 o/2 l/2 l/2

316 216 216 l/6

213 l/3 II3 313

18128 14/28 4/13 16128

(64%) (SO%] (31%) (57%)

patients affected/patients reported per parameter. non determined.

Laboratory

arteries are major targets of inflammatory process; however venules and capillaries 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, 23,24affecting patients with rheumatoid nodules25 and strongly positive serology. 26 The underlying physiopathological mechanism consists in immune complex deposition in the microcirculation,27, 28 leading to activation of neutrophils,29 platelets,30 macrophages31 and T-lymphocytes.’ The final deleterious event in tissues is probably related to free oxygen radicals and tumor necrosis factor-a (TNF-a). The management of RV is controversia14, ’ as with many autoimmune disorders. Scott and Bacon32 treated 100 patients with intermittent boluses of MP plus CPP and concluded this drug regimen led to healing and lowered relapse

Monitoring

No special laboratory parameters were used to monitor respopnse to PE procedures: 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 9

Improvement Stabilization Ab response Death n/n =

14

patients affected/patients reported per parameter. non determined.

Table 2.

n/n = ND =

Features 12 13

Clinical

patients evaluated/patients

12

212

13

14

15

16

212

l/2 l/2

l/6 316 l/6 II6

719 214 2l4

2l9

reported per group.

l

l/3 213

Total 12l22 8l22 5/22 3/22

(55%) (36%) (23%) (14%)

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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 stabilization. Our patients, treated with combined therapy, obtained a relatively good outcome, confirming previous reports. This literature review does not permit any clear-cut conclusions as no standard procedures were followed by the various groups. Our personal view about RV is that PE should be reserved for patients who cannot undergo immunosuppressive therapy (namely corticosteroids), those affected by very severe conditions (gangrene and/or mononeuritis multiplex) and for cases complicated by cryoglobulinemia.

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