|CONTINUING MEDICAL EDUCATION
|Year : 1990 | Volume
| Issue : 2 | Page : 101-106
Plasmapheresis in dermatology
AJ Kanwar, Surrinder Kaur, Murlidhar Rajagopalan
A J Kanwar
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Kanwar A J, Kaur S, Rajagopalan M. Plasmapheresis in dermatology. Indian J Dermatol Venereol Leprol 1990;56:101-6
Plasmapheresis is a special type of therapeutic modality which involves selective removal of plasma from the body and its replacement with a specific fluid. The term was first used by Abel et al in 1914. Initially however, the procedure was not adopted for clinical use as it required manual removal of large amounts of plasma which was time-consuming and cumbersome. The introduction of continuous and intermittent-flow centrifuges in 1960s has simplified the procedure. Plasmapheresis is now considered a practical procedure in clinical situations in which pathogenic materials can be effectively removed from the plasma., The pathogenic materials may be autoantibodies,[ 5] immune complexes or toxins like phytanic acids.
In simple language, plasmapheresis means drawing out a unit of blood at a time, centrifuging it, discarding the plasma, recombining the cells with a replacement fluid and returning the mixture to the patient.
| Rationale of plasmapheresis|| |
The rationale of plasmapheresis is to attempt to remove the pathogenic materials from the circulation and hence to achieve a therapeutic effect. The pathogenic substances may be: (a) Autoantibodies, e.g. myasthenia gravis, (b) Autoantibodies to epidermal cell membrane glycoproteins e.g. pemphigus, (c) Immune complexes e.g. systemic lupus erythematosus, (d) Monoclonal proteins e.g. hyperviscosity syndrome, (e) Toxins, e.g. mushroom poisoning, drug poisoning, (f) Phytanic acids
e.g. Refsum's disease, (g) Cryoglobulinst e.g. cryoglobulinemias, (h) Complement e.g. autoimmune diseases.
| Techniques of plasmapheresis|| |
Three methods of plasmapheresis are currently available: (a) Centrifugal separation, (b) Membrane separation, and (c) On-line plasma processing.
| Centrifugal separation|| |
This method is based on the differences in the sedimentation properties of the components of whole blood. A high speed central-core centrifuge allows incoming blood to form layers according to the densities which can be removed by precisely positional sampling ports.
| Membrane separation|| |
A variety of semi-permeable membranes with separation properties are now available. The dialysing membranes allow sieving of small molecules while membranes with large pores permit sieving of larger molecules.
| On-line plasma processing|| |
It consists of treatment of separated plasma, followed by recombination of the treated plasma with the cellular elements and reinfusion. This allows processing of large volumes of plasma during a single treatment and also the need for replacement fluids is minimized.
| Replacement fluids|| |
The various replacement fluids which can be used are fresh frozen or stored plasma albumin and purified protein fractions.
Except for thrombotic thrombocytopenic purpura in which plasma is the replacement fluid of choice, there are no other diseases foi which the optimal replacement fluids have beer identified. The usual practice has been to use albumin or purified protein fraction.
The common practice is to give first one third of the replacement fluid as isotonic saline and the remaining two thirds of 5% albumin 01 4% purified protein fraction. If the objective is clearance of circulating immune complexes, complement rich fluid must be given, while if autoantibodies are to be removed, replacement fluid lacking in complement should be transfused.
| Indications of plasmapheresis in dermatology|| |
These can be divided into four categories:
(a) Standard therapy-acceptable but not mandatory, Refsum's disease.
(b) Efficacious--conventional therapy is usually tried first, Systemic lupus erythematosus.
Vasculitis without renal disease. Type IIA familial hyperlipoproteinemia (homozygous).
(c) Inadequately testedPemphigus.
Progressive systemic sclerosis. Raynaud's phenomenon. Polymyositis!Dermatomyositis. Psoriatic arthritis.
Acquired immunodeficiency syndrome. Toxic epidermal necrolysis. Lucio phenomenon. Porphyria cutanea tarda.
(d) No demonstrated value in controlled trialsPsoriasis.
Pyoderma gangrenosum. Herpes gestationis.
| Refsum's disease|| |
The features of this rare inherited disorder include ichthyosis, chronic polyneuropathy. deafness and retinitis pigmentosa. There is in addition accumulation of phytanic acid in tissues. Plasmapheresis has been used as an adjunct to dietary restrictions of phytanic acid to reduce its levels in the blood and tissues.
| Systemic lupus erythematosus|| |
Marked but short-term clinical improvement has been observed in patients having systemic lupus erythematosus who had plasmapheresis alone or in combination with corticosteroids and cytotoxic drugs. However, no controlled study has yet proved the benefit of this therapy in systemic lupus erythematosus., It has not been possible to correlate the levels of antibodies to DNA and immune complexes to response to plasma exchanges. In fact, in one study where plasmapheresis alone was used to treat systemic lupus erythematosus, an immunologic deterioration occurred within one month of an initial good clinical response. This is probably due to the rebound phenomenon. At present, it would be advisable to use plasmapheresis as an adjunct therapy in severe lupus only.
| Familial hypercholesterolemia|| |
Patients with familial type IIa hyperlipoproteinemia have xanthomas and premature atherosclerosis along with a marked increase in the level of plasma cholesterol and low density lipoproteins. Plasmapheresis reduces the concentration of cholesterol and low-density lipoproteins resulting in resolution of the skin xanthomas., However, whether this can reverse or prevent atherosclerosis is not clear.
| Vasculitis|| |
In vasculitis associated with circulating immune complexes plasmapheresis is recommended in life-threatening situations. Improvement has been reported in polyarteritis nodosa, Henoch-Schoenlcin's purpura, cryoglobulinemia with vasculitis, kucocytoclastic vasculitis of unknown aetiology and rheumatoid vasculitis.,
| Pemphigus|| |
Plasmapheresis may be considered in patients with active and extensive disease who are not responding to conventional therapy. Whether it has a role in the initial treatment of the disease is not known. In a recent study, circulating levels of pemphigus antibodies. corticosteroid requirements and side effects of therapy were no better in 22 patients treated with a combination of low doses of prednisolone and plasmapheresis than in a control group of 18 patients treated only with prednisolone. These results are discordant from previous uncontrolled studies of plasmapheresis in pemphigus which had reported favourable results.,
The failure of plasmapheresis in pemphigus is due to the rebound phenomenon which occurs following this procedure. The rebound which results in an increase in the antibody levels is due to two different processes : (a) passive diffusion of extracellular immunoglobulins back into the circulation, and (b) lowering of the antibodies by plasmapheresis stimulating the feedback mechanism regulating the antibody levels resulting in a burst of new antibody synthesis that replaces and usually overshoots that which had been removed. 9sub To overcome these, plasmapheresis should be performed intensively and it should be coupled with measures to suppress the new antibody synthesis.
| Other autoimmune disorders|| |
Favourable results have been reported in uncontrolled trials of plasmapheresis in progressive systemic sclerosis, adult and childhood forms of polymyositis/dermatomyositis,,and psoriatic arthritis. However, these results need to be confirmed in controlled studies.
| Bullous pemphigoid|| |
Plasmapheresis may be useful as an adjunctive therapy for the treatment of bullous pemphigoid unresponsive to the standard treatment or in situations where the side effects of corticosteroid therapy predominate. Goldberg et a1 recently reported beneficial effect of plasmapheresis in a patient who had in addition to bullous pemphigoid, diabetes mellitus, severe fluid retention, hypertension and a myopathy.
| Drug-induced toxic epidermal necrolysis|| |
Kamanabroo et al reported five patients with severe drug-induced toxic epidermal necrolysis who improved rapidly after one to two plasma exchanges. Earlier, Gerard et al had reported benefit from this form of therapy in one patient with severe toxic epidermal necrolysis. As drug-induced toxic epidermal necrolysis is associated with a mortality rate of as high as 50% and some authors consider the role of corticosteroids in its management controversial, it may be worthwhile to try plasmapheresis in this disorder.
| Lucio phenomenon|| |
As plasmapheresis has been found to be effective for disease states characterized by circulating immune complexes, Wallach et al used this therapy with success in a 76-year-old patient with Lucio phenomenon. There was a dramatic clinical improvement, the ulcers healed rapidly and the nodules flattened, leaving atrophic pigmented scars.
| Psoriasis|| |
Clemmensen et a1 failed to observe beneficial effect of plasmapheresis in psoriasis in a controlled clinical study.
| Other conditions|| |
Presently, experience with plasmapheresis is limited in Behcet's disease, porphyria cutanea tarda. mixed connective tissue diseases and pruritus associated with cholestatic jaundice.
| Untoward effects of plasmapheresis|| |
Though plasmapheresis is a relatively safe procedure, it may result in certain adverse effects which can be broadly classified into three categories.
I Removal of beneficial components
(a) Coagulopathy : Due to the removal of coagulation components, patients ma have extensive haemorrhages.
(b) Drugs : Removal of phenytoin in a patien with central nervous system lupus may lead to reactivation of a previously controlled seizure situation.
(c) Removal of immuno-regulatory factors like, lymphokines in lupus erythematosus mal result in rebound phenomenon with exacer bation of the disease activity.
(d) Removal of proteins : Proteins maintair osmotic pressures and their replacement may result in fluid shifts resulting in nausea dizziness and even syncope. A rapid fluic shift can lead to severe problems in the patients with compromised cardiovascular functions.
II Infusion of harmful materials
(a) Hypersensitivity reactions to replacement fluids may occur such as urticaria, wheezing, angioedema and rarely anaphylaxis.
(b) Introduction of hepatitis virus or human immunodeficiency virus may occur if plasma is used as a replacement fluid and its origin is not known.
(c) Reaction to anticoagulants used in plasmapheresis e.g. thromocytopenia due to heparin and hypocalcemia due to citrate anticoagulants can also occur. Citrate toxicity may result in patients with liver diseases.,
(d) Air embolism may result if the equipment is not functioning properly.
III At the point of access, the in-dwelling catheter may lead to phlebitis, thrombosis and perforation; besides the catheters are a potential source of infection.
Most of the more than 50 deaths associated with plasmapheresis have been due to use of fresh plasma as a replacement fluid.
| Effective schedules of plasmapheresis|| |
During each plasmapheresis procedure, in which the volume exchange approachs the patient's plasma volume, about 50 to 60% of an intravascular substance is removed. Four or five such exchanges over a period of 7-10 days constitutes an adequate short-term therapy. This would hold true only if catabolism were to continue to balance the synthesis and intravascular shift throughout this time when the final concentration of a substance would be less than 10% of its initial concentration.  Since however, the actual concentration differs frequently, a sustained balance is unlikely. Therefore in disorders for which plasmapheresis is an effective therapy, serial clinical assessment and measurement of the pathogenic plasma factors should be done to decide the volume and the frequency of exchanges.
The kinetic characteristics of the material being removed should be taken into consideration while designing a protocol. For instance, the protocol for removal of a toxin or a drug would differ from that for the removal of auto antibodies.
| Future aspects and conclusions|| |
Though theoretically, plasmapheresis should improve a number of conditions, its efficacy remains unproven. However, in some of these conditions, it is reasonable to consider this form of therapy when conventional first-line therapy has failed. In spite of a number of side effects, it is still relatively safe compared. with other therapies of comparable efficacy. But it is a highly costly therapy. Apart from the cost of the machine, each plasmapheresis procedure costs anything between Rs 10,000 to Rs 25,000. In addition, immunosuppressive therapy is often recommended as an adjunct, negating some of the attractiveness of plasmapheresis from the standpoint of safety.
Though facilities for plasmapheresis are now available in several centres abroad, there is still a great deal of confusion concerning its role in therapy. Controlled trials are needed to assess its role in the disorders discussed above. Facilities for this procedure are also available at a few specialized centres in India. In our opinion, however, this should be resorted to perhaps only in a life saving desparate situation.
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