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  In this article
   Rationale of pla...
   Techniques of pl...
   Centrifugal sepa...
   Membrane separation
   On-line plasma p...
   Replacement fluids
   Indications of p...
   Refsum's disease
   Systemic lupus e...
   Familial hyperch...
   Vasculitis
   Pemphigus
   Other autoimmune...
   Bullous pemphigoid
   Drug-induced tox...
   Lucio phenomenon
   Psoriasis
   Other conditions
   Untoward effects...
   Effective schedu...
   Future aspects a...
   References

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CONTINUING MEDICAL EDUCATION
Year : 1990  |  Volume : 56  |  Issue : 2  |  Page : 101-106

Plasmapheresis in dermatology




Correspondence Address:
A J Kanwar


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How to cite this article:
Kanwar A J, Kaur S, Rajagopalan M. Plasmapheresis in dermatology. Indian J Dermatol Venereol Leprol 1990;56:101-6

How to cite this URL:
Kanwar A J, Kaur S, Rajagopalan M. Plasmapheresis in dermatology. Indian J Dermatol Venereol Leprol [serial online] 1990 [cited 2019 Apr 23];56:101-6. Available from: http://www.ijdvl.com/text.asp?1990/56/2/101/3492


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.[1] 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.[2] Plasmapheresis is now considered a practical procedure in clinical situations in which pathogenic materials can be effectively removed from the plasma.[3],[4] The pathogenic materials may be autoantibodies,[ 5][1] immune complexes[7] or toxins like phytanic acids.[8]

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 Top


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[5],[6] e.g. myasthenia gravis, (b) Autoantibodies to epidermal cell membrane glycoproteins[9] e.g. pemphigus, (c) Immune complexes[7] e.g. systemic lupus erythematosus, (d) Monoclonal proteins[10] e.g. hyperviscosity syndrome, (e) Toxins[11],[12] e.g. mushroom poisoning, drug poisoning, (f) Phytanic acids[8]

e.g. Refsum's disease, (g) Cryoglobulinst[13] e.g. cryoglobulinemias, (h) Complement[7] e.g. autoimmune diseases.


  Techniques of plasmapheresis Top


Three methods of plasmapheresis are currently available: (a) Centrifugal separation, (b) Membrane separation, and (c) On-line plasma processing.


  Centrifugal separation Top


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.[14]


  Membrane separation Top


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.[15]


  On-line plasma processing Top


It consists of treatment of separated plasma, followed by recombination of the treated plasma with the cellular elements and reinfusion.[16] This allows processing of large volumes of plasma during a single treatment and also the need for replacement fluids is minimized.


  Replacement fluids Top


The various replacement fluids which can be used are fresh frozen or stored plasma albumin and purified protein fractions.[17]

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.[18] 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 Top


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 Top


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.[8]


  Systemic lupus erythematosus Top


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.[19],[20] It has not been possible to correlate the levels of antibodies to DNA and immune complexes to response to plasma exchanges.[4] 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.[21] 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.[2]


  Familial hypercholesterolemia Top


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.[22],[23] However, whether this can reverse or prevent atherosclerosis is not clear.[4]


  Vasculitis Top


In vasculitis associated with circulating immune complexes plasmapheresis is recommen­ded in life-threatening situations.[2] Improvement has been reported in polyarteritis nodosa, Henoch-Schoenlcin's purpura, cryoglobulinemia with vasculitis, kucocytoclastic vasculitis of unknown aetiology and rheumatoid vasculitis.[24],[25]


  Pemphigus Top


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.[9] 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.[27],[28]

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.[9]


  Other autoimmune disorders Top


Favourable results have been reported in uncontrolled trials of plasmapheresis in progres­sive systemic sclerosis,[29] adult and childhood forms of polymyositis/dermatomyositis,[30],[31]and psoriatic arthritis.[32] However, these results need to be confirmed in controlled studies.


  Bullous pemphigoid Top


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.[33] Goldberg et a1[34] 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 Top


Kamanabroo et al[35] reported five patients with severe drug-induced toxic epidermal necro­lysis who improved rapidly after one to two plasma exchanges. Earlier, Gerard et al[36] 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[37] consider the role of corticosteroids in its management controversial, it may be worthwhile to try plasmapheresis in this disorder.


  Lucio phenomenon Top


As plasmapheresis has been found to be effective for disease states characterized by circulating immune complexes, Wallach et al[33] 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 Top


Clemmensen et a1[39] failed to observe bene­ficial effect of plasmapheresis in psoriasis in a controlled clinical study.


  Other conditions Top


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 Top


Though plasmapheresis is a relatively safe procedure, it may result in certain adverse effects which can be broadly classified into three categories.[16]

I Removal of beneficial components

(a) Coagulopathy : Due to the removal of coagulation components, patients ma have extensive haemorrhages.[16]

(b) Drugs : Removal of phenytoin in a patien with central nervous system lupus may lead to reactivation of a previously controlled seizure situation.[16]

(c) Removal of immuno-regulatory factors like, lymphokines in lupus erythematosus mal result in rebound phenomenon with exacer bation of the disease activity.[40]

(d) Removal of proteins : Proteins maintair osmotic pressures and their replacement may result in fluid shifts resulting in nausea dizziness and even syncope.[4] A rapid fluic shift can lead to severe problems in the patients with compromised cardiovascular functions.[4]

II Infusion of harmful materials

(a) Hypersensitivity reactions to replacement fluids may occur such as urticaria, wheezing, angioedema and rarely anaphylaxis.[4]

(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.[4],[16]

(d) Air embolism may result if the equipment is not functioning properly.[16]

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.[16]

Most of the more than 50 deaths associated with plasmapheresis have been due to use of fresh plasma as a replacement fluid.[4]


  Effective schedules of plasmapheresis Top


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. [4] 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.[4]

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.[16]


  Future aspects and conclusions Top


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.[2] 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.[4] 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.[2]

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.

 
  References Top

1.Abel JJ, Rowntree LG and Turner BB : Plasma removal with return of corpuscles (plasmapheresis), J Pharmacoi Exp Therap, 1914; 5 : 625-641.  Back to cited text no. 1    
2.Barnes A, Clough JD, Gifford RW et al : Current status of therapeutic plasmapheresis and related techniques-report of the AMA panel on thera­peutic plasmapheresis, JAMA, 1985; 253 : 819-825.  Back to cited text no. 2    
3.Millward BL and Hoeltge GA : The historical development of automated hemapheresis, J Clin Apheresis, 1982; 1 : 25-32.  Back to cited text no. 3    
4.Shumak KH and Rock GA : Therapeutic plasma exchange, N Eng J Med, 1984; 310 : 762-769.  Back to cited text no. 4    
5.Dau PC, Lindstrom JM, Cassel CK et al : Plasma­pheresis and immunosuppressive drug therapy in myaesthenia gravis, N Eng J Med, 1977; 297 :1134­ 1140.  Back to cited text no. 5    
6.Newsom-Davis J, Pinching AJ, Vincent A et al Function of circulating antibody to acetylcholine receptor in myaesthenia gravis : investigation by plasma exchange, Neurol (Minneap), 1978; 28 266-272.  Back to cited text no. 6    
7.Lockwood CM, Worlledge S. Nicholas A et al Reversal of impaired splenic function in patients with nephritis or vasculitis (or both) by plasma exchange, N Eng J Med, 1979; 300 : 524-530.  Back to cited text no. 7    
8.Gibberd FB, Billimoria JD, Page NGR et al Heredopathia at actica polyneuritiformis(Refsum's disease) treated by diet and plasma exchange, Lancet, 1979; 1 : 575-578.  Back to cited text no. 8    
9.Bystryn JC : Plasmapheresis therapy of pemphigus, Arch Dermatol, 1988; 124 : 1702-1704.  Back to cited text no. 9    
10.Schwab PJ and Fahey JL : Treatment of Walden­strom's macroglobulinemia by plasmapheresis, N Eng J Med, 1960; 263 : 574-579.  Back to cited text no. 10    
11.Mercuriali F and Sirchia G : Plasma exchange for mushroom poisoning, Transfusion, 1977; 17 : 644­646.  Back to cited text no. 11    
12.Dearnaley DR and Martin MFR : Plasmapheresis for paraquat poisoning, Lancet, 1978; 1 : 162.  Back to cited text no. 12    
13.Berkman EM and Orlin JB : Use of plasmapheresis and partial plasma exchange in the management of patients with cryoglobulinemia, Transfusion, 1980; 20 : 171-178.  Back to cited text no. 13    
14.McCullough J, Fortuity IE, Kennedy BJ et al Rapid plasma exchange with the continuous flow centrifuge, Transfusion, 1973; 13 : 94-99.  Back to cited text no. 14    
15.Solomon BA : Membrane separations : techno­logical principles and issues,Trans Amer Soc Artit Int Organs, 1981; 27 : 345-350.  Back to cited text no. 15    
16.Clough JD and Paganini EP : Therapeutic plasma­pheresis, Postgrad Med, 1984; 75 : 77-84.  Back to cited text no. 16    
17.Wenz B, Barland P : Therapeutic intensive plasma­pheresis, Semin Hematol, 1981; 18 : 147-162.  Back to cited text no. 17    
18.Barnes JJ and Khurana M : Treatment of throm­botic thromhocytopenic purpura with plasma, N Eng J Med, 1977; 297 : 1386-1389.  Back to cited text no. 18    
19.Verrier Jones J, Cumming RH, Bucknall RC et al Plasmapheresis in the management of acute syste­mic lupus erythematosus? Lancet, 1976; 1 709-711.  Back to cited text no. 19    
20.Parry HE, Moran CJ, Snaith ML et al : Plasma exchange in systemic lupus erythematosus, Ann Rheum Dis, 1981; 40 : 224-228.  Back to cited text no. 20    
21.Wei N, Klippel JH, Huston DP et al : Randomized trial of plasma exchange in mild systemic lupus erythematosus, Lancet, 1983; 1 : 17-22.  Back to cited text no. 21    
22.Thompson GR, Lowenthal R and Myant NB Plasma exchange in the management of homozy­gous familial hypercholesterolaemia, Lancet, 1975; 1 : 1208-1211.  Back to cited text no. 22    
23.King MEE, Breslow JL and Lees RS : Plasma­exchange therapy of homozygous familial hyper­cholesterolemia, N Eng J Med, 1980; 302 : 1457­1459.  Back to cited text no. 23    
24.Kauffman RH and Houwes DA : Plasmapheresis in rapidly progressive Henoch-Schoenlein glome­rulonephritis and the effect on circulating IgA immune complexes, Clin Nephrol, 1981; 16 : 155­160.  Back to cited text no. 24    
25.Wysenbeek AJ, Calabrese LH, Mandel DR et al Limited plasmapheresis in fulminant leucocyto­clastic vasculitis, J Rheumatol, 1982; 9 :315-318.  Back to cited text no. 25    
26.Guillaume JC, Roujeau IC, Morel P et al : Con­trolled study of plasma exchange in pemphigus, Arch Dermatol, 1988; 124 : 1659-1663.  Back to cited text no. 26    
27.Roujeau JC, Andre C, Fabre MJ et al : Plasma exchange in pemphigus : uncontrolled study; often patients, Arch Dermatol, 1983; 119 : 215 221.  Back to cited text no. 27    
28.Cotteril JA, Barker DJ, Milard LG et al : Plasma exchange in the treatment of pemphigus vulgaris, Brit J Dermatol, 1978: 98 : 243-245.  Back to cited text no. 28    
29.Dau PC, Kahaleh MB and Sagebiel RS : Plasma­pheresis and immunosuppressive drug therapy in sclcroderma, Arth Rheumatol, 1981; 24: 1128­1136.  Back to cited text no. 29    
30.Bennington JL and Dare PC : Patients with poly­myositis and dermatomyositis who undergo plasma­pheresis therapy, Arch Neurol, 1981; 38 : 553-560.  Back to cited text no. 30    
31.Brewer EJ, Giannini EG, Rossen RD et al : Plasma exchange therapy of a childhood onset dermato­mpositis patient, Arth Rheumatol, 1980; 23 : 509­ 513.  Back to cited text no. 31    
32.Wallace DJ, Goldfinger D, Thompson-Breton R et al : Advances in the use of therapeutic nheresis for the management of rheumatic diseases, Semin Arth Rheumatol, 1980; 10 : 81-91.  Back to cited text no. 32    
33.Roujeau JC, Guillaume JC, Morel P et al : Plasma exchanges in bullous pemphigoid, Lancet, 1984; 2: 486-489.  Back to cited text no. 33    
34.Goldberg NS, Robinson JK, Roenigk HH et al Plasmapheresis therapy for bullous pemphigoid, Arch Dermatol, 1985; 121 : 1484-1485.  Back to cited text no. 34    
35.Kamanabroo D, Schmitz-Landgraf W and Czar­netzski BM: Plasmapheresis in severe drug-induced toxic epidermal necrolysis, Aich Dermatol, 1985; 121 : 1548-1549.  Back to cited text no. 35    
36.Gerard A, Roche G, Presles O et al : Drug-induced Lyell's syndrome : nine cases, Therapies 1982; 37 475-480.  Back to cited text no. 36    
37.Lyell A : Toxic epidermal necrolysis (The scalded skin syndrome) : a reappraisal, Brit J Dermatol, 1979; 68 : 355-358.  Back to cited text no. 37    
38.Wallach D, Cottenol F, Bussel A et at : Plasma exchange therapy in Lucio's phenomenon, Arch Dermatol, 1980; 116 : 1101.  Back to cited text no. 38    
39.Clemmensen OJ, Andersen R and Andersen E Plasmapheresis in the treatment of psoriasis : a controlled clinical study, J Amer Acad Dermatcl, 1983; 8 : 190-192.  Back to cited text no. 39    
40.Schlansky R, DeHoratius R.1, Pincus T et al Plasmapheresis in systemic lupus erythematosus a cautionary note, Arth Rheumatol, 1981; 24 49-53.  Back to cited text no. 40    




 

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