plasma exchange for treatment of intractable psoriasis

Artificial Organs 7(4):450-453, Raven Press, New York 0 1983 International Society for Artificial Organs

Plasma Exchange for Treatment of Intractable Psoriasis

Kenji Maeda, Tom Shinzato, Masaaki Naotsuka, Masatsune Usuda, Ryozo Sezaki, Toshimitsu Niwa, Shunsuke Kawaguchi, "Akira Saito,*Naoki Yamanaka, and

*Kazuhiro Ohta

Nagoya University Branch Hospital, and *The Bio-Dynamics Research Institute, Nagoya, Japan

Abstract: Hemofdtration and plasma exchange, using a plasma separator with membranes, were used in 14 psoriatic patients. The efficacies of the treatments were compared. Among the patients, 13 were treated with hemofiltration and/or direct hemoperfusion, 5 experienced complete remission, 5 improved, and 3 remained unaffected. In these 3 cases, plasma exchange was performed. The first patient, who suffered from psoriasis pustulosa with arthropathica, achieved complete remission with only

two treatments of 2-L plasma exchange. Joint pain was also eliminated. Both skin lesions and joint pain were markedly improved in the second patient, who suffered from psoriasis vulgaris with arthropathica. The third patient showed marked improvement with only two plasma exchanges, and is under continuing observation. Key Words: Psoriasis-Plasma exchange-Plasmapheresis- Hemofiltration-Plasma separation-Membrane separator.

Psoriasis is an intractable disease. With various conventional therapies, temporary relief can be achieved, but relapses are frequent. For pustular psoriasis cases, there is no treatment at present. By administration of analgesics to the psoriasis patient suffering from arthropathica, pain can be relieved temporarily; however, it never disappears completely. Since the first report of dialysis being an effective therapy for psoriasis (l), many reports have followed. One states the ineffectiveness of conventional dialysis with cellulose membrane (2); another the remarkable effect of hemofiltration (HF) (3); and yet another the effectiveness of direct hemoperfusion (DH) with activated charcoal (4). The true effectiveness of these solute-removal therapies for psoriasis, however, remains controversial. In this article, the following are discussed concerning psoriasis treatment with various membranes: (a) Can psoriasis be treated with solute-removal therapies using semipermeable membranes? (b) What is the effect of heparin administration on psoriasis? (c) What is the effect on treatment of different membrane processes, including dialysis with cellulose

Received March 1982; revised September 1982. Presented in part, at the Second Tutzing Symposium on Chem-

ical Engineering in Medicine: New Membranes in Medical Treat- ment, September 14-17, 1981, Castle Tutzing, F.R.G.

Address correspondence and reprint requests to Dr. Maeda at Nagoya University Branch Hospital, 1-4, Daiko-cho I-chome, Higashi-ku, Nagoya 461, Japan.

membrane, H F with polyacrylonitrile membrane, and plasma exchange (PE) with cellulose acetate membrane?

METHODS

Fourteen psoriasis patients (13 male and 1 female, between 27 and 71 years of age) were treated with HF [Hospal RP-6 filter (Hospal AG, Basel, Swit- zerland) with polyacrylonitnle membrane] receiving 10-18 L of replacement fluid for each treatment a n d or DH (Asahi Hemosorba; Asahi Medical Co., Ltd., Tokyo, Japan) three times a week for 2-13 months. Plasma exchange was performed in three male patients whose clinical data are shown in Table l. In the PE, which used a plasma separator (Asahi MA- 2500) with cellulose acetate membrane, 2,000 ml of plasma was exchanged during each treatment. As a substitution fluid, fresh frozen plasma in the same volume as the removed plasma or 5% human albumin solution (Na+ 140 mEq/L; K + 4.0 mEq/L; Ca2+ 4.0 mEq/L; Mg2+ 1.0 mEq/L; acetate 38 mEq/ L; C1- 111 mEq/L) was used.

Heparin was used in all the above-mentioned treatments, so its effect on psoriasis could be clar- ified. Heparin was given to four male patients (16- 67 years of age) through an intravenous infusion line (Table 2). In three of these cases, initial administration of 50 mg of heparin was followed by an injec- tion of 10 mg each hour three times a week, 27-42

450

PSORIASIS TREATMENT WITH PLASMA EXCHANGE 451

TABLE 1. Psoriasis patients treated with heniofiltration (HF)idirect hernoperfusion (DH) arid plasma exchange (PE)

No. of Patient Age (yr) Sex Diagnosis Treatment treatments Effect

1" (Y.K.)

2 (R.O.) 3 (T.T.) 4 (S.S.) 5" (H.H.)

6 (H.B.) 7 (Y.M.) 8 (H.I.) 9 (Y.O.)

10 (H.M.) I 1 (K.T.)

12 (Y.O.) 13 (T.Y.) 14 (M.T.)

~

65 M

67 M

64 M 31 M 53 M 45 M 47 M 35 M 52 M 63 M 37 M 27 F 71 M

37 M 36 M 30 M

Pustular Arthropathica Pustular Arthropathica Pustular Vulgaris Pustular Vulgaris Vulgaris Arthropathica Vulgaris Vulgaris Vulgaris Vulgaris With

Vulgaris Vulgaris Vulgaris

erythrodermia

H F 38

PE 2

H F + DH 48 H F + D H 71 H F + DH 27 H F + D H 45 PE 2 PE 2 H F 24 H F 27 H F + DH 38 H F 39 H F + DH 18

H F + DH 32 H F 34 H F 36

Complete remission

Complete remission

Complete remission Complete remission Complete remission Complete remission Improved Improved Improved Improved Improved Improved Improved

Ineffective Ineffective Ineffective

Patients 1 and 5 experienced complete remissions, but subsequently relapsed. Therefore, plasma exchange was performed, and the therapeutic efficacies of hemofiltration and plasma exchange were compared

times in total. In one case (patient Y.K.), who suffered a relapse after long-term remission, heparin administration by the same method was continued for 26 consecutive days.

RESULTS The therapeutic efficacies of H F and/or DH and

PE are summarized in Table 1. Of the 13 patients who were treated with H F or HF/DH, five were in complete remission, five improved, and three were unaffected. The treatment for the improved cases was stopped between the 18th and 39th treatments. In the group showing no improvement, the treatment was stopped between the 32nd and 36th treatments. Five cases had complete remission after 27- 71 treatments for 3-11 months. Two of these, each of whom suffered a relapse about 2 years later, received two plasma exchanges: one patient achieved complete remission and the other almost achieved one also. Patient H.B., who was treated with PE

only twice, showed marked improvement. Case reports for some of the patients follow.

Case Y.K. (male; 35 years old; pustular psoriasis with arthropathica)

At 39 years of age, the first stage of psoriasis vulgaris appeared (Fig. 1 ) . After that, the patient complained of progressively worsening joint pain. At 57 years of age, a glucocorticoid was administered for this pain. The skin lesions and joint pain sometimes lessened and sometimes increased. At age 64, the lesions changed to a pustular type, and at 65 years of age, joint pain worsened and he was remarkably debilitated. Since his life was in danger, HF was started in July 1978, using a Hospal RP-6 filter with 18 L of replacement fluid. Thirty-eight treatments (three times a week over 3 months) re- sulted in complete remission. With improved skin lesions, joint pain disappeared and the systemic condition showed marked improvement. Complete remission continued for 2 years, but the lesions and

TABLE 2. Examination of the effeets of heparin on psoriasis

No. of Total amount of Patient Age (yr) Diagnosis administrations heparin (mg) Effect

1 (Y.K.) 67 Pustular 26 (daily) 2,600 Ineffective

2 (R.O.) 64 Pustular 27 (3 times a week) 2,430 Ineffective 3 (T.T.) 31 Vulgaris 42 (3 times a week) 3,780 Ineffective 4 (Y.N.) 16 Vulgaris 36 (3 times a week) 3,240 Ineffective

Arthropathica

Arfif Organs, Vul. 7, No. 4 , 1983

452 K. MAEDA ET AL.

1 1978 July

Oct. 1

1980 Aug. J Oct.

Dee' 1 1981 Feb. J

March

April

Hemofiltration using Hospal RP-6 filter, 18 L of substitution fluid (38 treatments)

Complete remission (without joint pain)

Knee joint pain recurs Aggravation of knee joint pain; relapse

of pustular psoriasis Heparin administration (50 mg at first;

thereafter, 10 mg, 5 times/h) (26 treatments)

Plasma exchange (2,000 ml of fresh frozen plasma) (two treatments)

Complete remission

FIG. 1. Patient Y.K., 65-year-old male, with pustular psoriasis and arthropathica. With 38 hemofiltration treatments over 3 months, the patient experienced complete remission; however, after a relapse, only two plasma exchange treatments produced complete remission.

joint pain recurred in October 1980. Heparin treatment was begun in December 1980, for 26 consecutive days. The skin lesions changed, but progres- sive improvement was not observed. The skin lesions and joint pain were observed for an additional 2 months after heparin administration, but aiain no improvements were observed.

The patient could not walk by himself due to increased joint pain; the systemic condition worsened. Therefore, in March 1981, PE treatment was performed. Two thousand milliliters of plasma was removed and the same volume of fresh frozen plasma was infused. The skin lesions improved. A second PE treatment of 2,000 ml was then performed. Com- plete remission was achieved, together with the relief of joint pain. To date, there has been no recurrence of symptoms. Thus, this patient achieved complete remission with only two PE treatments. Case R.O. (male; 65 years old; pustular psoriasis)

At 59 years of age, skin lesions were observed and the patient was diagnosed as having psoriasis vulgaris. At 63 years of age, erythrodermia was found and exudative changes became apparent. At age 64, some pustular change was observed. Begin- ning in October 1978, 48 DH and HF treatments were performed over 5 months. Although complete remission was achieved, gastric cancer was discov- ered in 1979, and the patient died in December 1980. Case T.T. (male; 31 years old; psoriasis vulgaris)

This patient (Fig. 2) suffered from psoriasis vulgaris at the age of 23. Regardless of various therapies, no improvements were observed. Beginning in November 1978, heparin was administered three times a week for 3 months, 42 times in total. The skin lesions improved slightly after 1 month, but

subsequently deteriorated and returned to their preadministration state. It was concluded that administration of heparin was ineffective. Therefore, in February 1979, combined treatments of HF and DH were performed 20 times over 2 months, followed by 59 H F treaments over 9 months. He may have achieved complete remission with this course of treatment. To date, as of December 1979, the lesions have not reappeared. For younger patients with psoriasis vulgaris, long-term treatment seems to be required. Case H . H . (male)

This patient was first diagnosed as having psoriasis vulgaris in 1972. Beginning in December 1978, treatment with HF and DH was administered, and, in April 1979, he experienced complete remission, which continued for 26 months. However, in June 1981, relapse of psoriasis vulgaris was observed. At this time, with only two PE treatments, he is in almost complete remission.

As shown in Table 3, three cases achieved complete remission or marked improvement with only two PE treatments. Therefore, PE appears to be a remarkably effective treatment for psoriasis. Effect of heparin administration

As shown in Table 2, the total number of heparin administrations ranged from 26 to 42 in four patients. In two pustular psoriasis cases, slight reduc- tions of skin lesions were observed but the condi- tions soon worsened. There were no observable changes in other psoriasis vulgaris cases. It can be concluded from these results that the therapeutic benefits did not depend on administration of heparin.

1970 Diagnosed as psoriasis vulgaris 1978 Oct. Heparin administration (50 mg at first;

thereafter 10 mg, 4 tirnes/h, 3 times/ week) (42 treatments)

Hemofiltration + direct hemofiltration (20 treatments)

Mar. Hemofiltration (3 timeslweek) (59 treatments)

lg7’ Feb‘

Complete remission

No recurrence seen for 20 months

1979 Dec.

1981 Aug.

FIG. 2. Patient T.T., 31-year-old male, with psoriasis vulgaris. Heparin was administered at first, resulting in temporary reduction of skin lesions. The treatment was deemed ineffective. Combined hemofiltration and direct hemofiltration was performed 20 times over 2 months, followed by 59 hemofiltration treatments over 9 months. The patient may be in complete remission; to date (>20 months), symptoms have not recurred.

Art i forgans , Vol. 7, No. 4, 1983

PSORIASIS TREATMENT WITH PLASMA EXCHANGE 453

TABLE 3. Treatmerzt of pxwiasis with plusnia exchange

Exchange Plasma Substitution volume No. of

Patient Age (yr) Sex Diagnosis separator fluid per treatment treatments Effect

1 (Y.K.) 67 M Pustular MA-2500 Fresh, frozen 2 L 2 Complete

2 (H.B.) 35 M Vulgaris MA-2500 5% Albumin 2 L 2 Markedly

3 (H.H.) 47 M Vulgaris MA-2500 5% Albumin 2 L 2 Markedly

Arthropathica plasma remission

Arthropathica solution improved

improved solution

DISCUSSION

The efficacy of solute-removal therapies for psoriasis seems to differ with the type of lesion. Com- plete remission seems to be most easily achieved for pustular psoriasis cases and those cases with severe exudative change. In general, better efficacy is seen with older patients.

When the efficacy of various artificial membranes was examined, dialysis treatment with cellulose membrane had little benefit, and some investigators have reported a total ineffectiveness. Our experi- ence demonstrates that H F with polyacrylonitrile membrane was superior. From the results obtained in H F treatment, plasma separation, which removes large molecules, should be more beneficial in a short period than HF, assuming the efficacy of treatment depends upon the removal of large molecular substances. Therefore, PE was performed in patient Y.K., in whom the lesions recurred after 2 years. He may have a complete remission after only two PE treatments, which constitutes a far shorter treatment time than was required for HF (38 treatments). Patient H.B. (male, 35 years old, psoriasis vulgaris with arthropathica) also improved. Patient H.H., in whom the lesion recurred after 26 months, experienced marked improvement with only two PE treatments. Additionally, it was reported that a 69-year- old female patient with psoriasis, in whom plasmapheresis was performed to treat myasthenia gravis, achieved complete remission of the psoriasis (5).

PE appears to be the most effective of the solute- removal therapies for pustular psoriasis, arthropathica, and psoriasis with severe exudative changes. Younger patients with plaque psoriasis should be made aware of the indications, and sub- sequent long-term treatment should be performed.

When the effectiveness of hemodialysis is compared with that of HF, the latter is superior. With regard to H F treatment of plaque psoriasis, in patient T.T., long-term treatment over l l months re- sulted in complete remission. With PE, however, complete remission was achieved with only two

treatments. With such dramatic effects after only two PE treatments, it does not seem plausible that the effects are due to certain substances being ad- sorbed onto the membrane or that the membranes are releasing some substance. If such a substance is in the circulation, it may be removed more effec- tively by PE. The effectiveness of HF appears to be related to the removal of some substances that can only be eliminated over long-term therapy with the polyacrylonitrile membrane. This assumption is supported by the above-mentioned efficacy of PE. Tagami et al. (6,7) reported that a leukotactic factor existed in psoriatic scale that had a molecular weight of approximately 10,000.

CONCLUSIONS

Hemofiltration treatment has been performed three times a week for 3-6 months in pustular psoriasis cases, and complete remissions were acheved. For plaque psoriasis, although a long-term treatment over 11 months was required, complete remission was achieved. With HF, both arthropathica and skin lesions disappeared. It takes a much shorter period to achieve a complete remission in PE than in HF. Joint pain disappeared completely with plasma exchange in two patients having arthropathica.

REFERENCES 1.

2.

3 .

4.

5 .

6.

7.

McEvoy J, Kelly AMT. Psoriatic clearance during hemodialysis. Ulster Med .I 1976;45:76. Nissenson AR, Rapaport M, Gordon A, Narins RG. Con- trolled study demonstrates that psoriasis is not improved by hemodialysis. Kidney Int 1978;14:682. Maeda K, Ohki T, Kawaguchi S, Saito A, Niwa T, Sezaki R, Kobayashi K, Yamamoto Y, Asada H, Ohta K. Chemical analysis of the nails of patients with psoriasis treated with dialysis. Artif Organs 1979;3(suppl): 166-9. Sideman S, Chang TMS, eds. Hemoperfusion: kidney and liver support and detoxification (part 1). New York: Hemi- sphere Publishing, 1980:349-55. Peter C. Resolution of psoriasis during plasmapheresis therapy. Arch Dermatol 1979;115:1171. Tagami H, Ofuji S. Leukotactic properties of soluble substances in psoriasis scale. Br J Dermatol 1976;95: 1 . Tagami H, Ofuji S. Characterization of a leukotactic factor derived from psoriatic scale. Br J Dermatol 1977;97:509.

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plasma exchange for treatment of intractable psoriasis

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