British Journal of Dermatology (1979} ioi, 87.
Systemic lupus erythematosus in pregnancy treated with plasmapheresis HILARY C.HUBBARD AND B.PORTNOY The Skin Hospital, University of Manchester School of Medicine, Quay Street, Manchester M3 3HL Accepted for publication i November 197S
SUMMARY
A young woman developed severe systemic lupus erythematosus (SLE) at the beginning of her second pregnancy: her disease was extremely difficult to control and the baby died unexpectedly when 8 weeks old. She became very ill at the same rime in her third pregnancy; plasmapheresis appeared to make her management easier, and the 7-month-old baby is doing well.
Initially plasma exchange was thought to be most successful in those with acute SLE who have immune complexes in the serum; this padent had no detectable immune complexes. CASE REPORT
A 23-year-old woman was admitted to the Skin Hospital in August 1975 when 2 months pregnant. She was extremely ill with a crusted erythematous rash on the face (Fig. i), a bullous rash on the arms, necrotic vasculitis of the fingers, and a livid erythema on other exposed areas. Systemic lupus erythematosus (SLE) was suspected and the diagnosis confirmed by the presence of LE cells, antinuclear factor, a neutropenia and compatible histology. The disease was eventually controlled on 80 mg prednisolone a day. She was sent home in November on 35 mg a day, and this was gradually reduced so that just before delivery she was on 20 mg daily. The baby appeared normal at birth, but died a 'cot death' at 8 weeks. Her first pregnancy in 1973 was normal, although the baby was born by caesarean section because of a brow presentation, and was small for dates; that child is alive and well. Shortly after the death of the second child the patient was admitted with a relapse of SLE: 150 mg azathioprine was added to 60 mg prednisolone daily and she improved on this regime. The azathioprine was discontinued 8 months later when she became hypersensitive to it: a new blotchy erythematous rash appeared on the face which disappeared when the drug was stopped and reappeared when it was resumed. Within 4 weeks of stopping azathioprine, and while on 200 mg chloroquine and 20 mg prednisolone daily, she became pregnant again against medical advice. As the disease was not controlled on 60 mg prednisolone, plasmapheresis was carried out on five occasions during i week, when * This case was presented to the North of England Dermatological Society on 16 May 1978. 0007-0963/79/0700-0087 $02.00
V' 1979 British Association of Dermatologists
87
H.C.Huhhard and B.Portnoy
FIGURE I. Crusted erythematous rash on face of patient.
she was 15 weeks pregnant, with a total exchange of 9 1. Her most disabling feature at this stage was vasculitis of the fingers which improved dramatically after treatment, and she was discharged home a month earlier than in the previous pregnancy. A further exchange was carried out 3 weeks later but no further attempts were made because of poor veins. The patient had a normal baby by caesarean section, and is now maintained on 15 mg prednisolone a day. Investigations During her second pregnancy: ESR 75 mm/h; WBC 1600 m m ^ platelets I26,ooo;mm'; LE cells present; ANF positive 4- + ; a skin biopsy from the forearm showed the histological features of bullous lupus erythematosus, and immunofiuorescent studies showed IgG at the dermo-epidermal junction. During the third pregnancy while she was on high doses of systemic steroids: ANA i :2ooo homogenous IgG, anti DNA antibody 25 units, ml (< 10, normal). At all times serum complement, immunoglobulins, proteins, creatinine, WR, urine microscopy and chest X-rays have been normal: no immune complexes (Ciq) were found.
SLE treated with plasmapheresis
f^
DISCUSSION
Plasma exchange has been used successfully in rhesus disease, myasthenia gravis and renal disease as well as SUE {British Medical JotimaU 1978). Initially 1-5-3 1 are removed a day and replaced with fresh or dried plasma, or a plasma substitute; in pregnancy fresh plasma must be used. When the disease is controlled, maintenance exchanges are carried out at weekly to monthly intervals. Occasionally it is necessary to insert an arteriovenous shunt if the veins are very poor, and some centres use concurrent immunosuppressive drugs (Moran et al.^ 1977). Verrier Jones et a!. (1976) described eight patients with SLE, seven of whom had high anti-DNA antibodies and four had high levels of immune complexes; the latter group did well with plasmapheresis. Since then patients without immune complexes detectable by the methods used have benefited from plasmapheresis (Bacon, personal communication): the explanation for this is not clear, but it is possible that factors other than immune complexes are removed or that present techniques do not detect all of them. There are no complications from intensive plasmapheresis in pregnancy apart from slight nausea (Fraser et ai, 1976). A post mortem on the second baby showed a scabbed lesion 7 mm x 7 mm on the right arm at the site of a neonatal BCG vaccination, and the adrenals were small with fatty depletion. Although plasma immunoglobulins and cortisols were normal shortly after birth, it may be unwise to give these children BCG so early in life. This patient is also interesting because she subsequently became pregnant within a month of stopping azathioprine while she was on chloroquine and has had a normal baby. Plasmapheresis, although time consuming, expensive and cumbersome for routine use, can clearly play a useful part in the management of fulminating SLE, where there is a need to reduce the dose of oral steroids as in pregnancy, or where cytotoxic drugs are contraindicated because of pancytopenia or hypersensitivity. ACKNOWLEDGMENTS
We are very grateful to Dr Hull, Dr Stevens and Dr Vosylius of the Haematology Department for carrying out the plasmapheresis and to Dr Holt, Rheumatologist at the Manchester Royal Infirmary for helpful advice. REFERENCES BRirisH MEDICAL JOURNAL (1978) Plasmapheresis (leading article), i, loir. FRASER, I.D., BOTHAMLEY, J.E., BENNETT, M.O., AIRTH, G.R., LEHANE, D . , MCCARTHY, M . & ROBERTS, F . M .
(1976) Intensive antenatal plasmapheresis in severe rhesus isoimmunisation. Lancet, i, 6. MORAN, C.J., PARRY, H.F., MOWBRAY, J., RICHARDS, J . D . M . & GOLDSTONI-, A . H . (1977) Plasmapheresis in
Systemic Lupus Erythematosus. British Medical Journal, i, 1573. VERRIER JOKES, J., BUCNALL, R . C , CUMMING, R.H., ASI'LIN, C M . , FRASER, I.D., BOTHAMLEY, J., DAVIS, P. &
HAMBLIN, T.J. (1976) Plasmapheresis in the management of acute lupus erythematosus. Lancet, i, 709.
Systemic lupus erythematosus in pregnancy treated with plasmapheresis HILARY C.HUBBARD AND B.PORTNOY The Skin Hospital, University of Manchester School of Medicine, Quay Street, Manchester M3 3HL Accepted for publication i November 197S
SUMMARY
A young woman developed severe systemic lupus erythematosus (SLE) at the beginning of her second pregnancy: her disease was extremely difficult to control and the baby died unexpectedly when 8 weeks old. She became very ill at the same rime in her third pregnancy; plasmapheresis appeared to make her management easier, and the 7-month-old baby is doing well.
Initially plasma exchange was thought to be most successful in those with acute SLE who have immune complexes in the serum; this padent had no detectable immune complexes. CASE REPORT
A 23-year-old woman was admitted to the Skin Hospital in August 1975 when 2 months pregnant. She was extremely ill with a crusted erythematous rash on the face (Fig. i), a bullous rash on the arms, necrotic vasculitis of the fingers, and a livid erythema on other exposed areas. Systemic lupus erythematosus (SLE) was suspected and the diagnosis confirmed by the presence of LE cells, antinuclear factor, a neutropenia and compatible histology. The disease was eventually controlled on 80 mg prednisolone a day. She was sent home in November on 35 mg a day, and this was gradually reduced so that just before delivery she was on 20 mg daily. The baby appeared normal at birth, but died a 'cot death' at 8 weeks. Her first pregnancy in 1973 was normal, although the baby was born by caesarean section because of a brow presentation, and was small for dates; that child is alive and well. Shortly after the death of the second child the patient was admitted with a relapse of SLE: 150 mg azathioprine was added to 60 mg prednisolone daily and she improved on this regime. The azathioprine was discontinued 8 months later when she became hypersensitive to it: a new blotchy erythematous rash appeared on the face which disappeared when the drug was stopped and reappeared when it was resumed. Within 4 weeks of stopping azathioprine, and while on 200 mg chloroquine and 20 mg prednisolone daily, she became pregnant again against medical advice. As the disease was not controlled on 60 mg prednisolone, plasmapheresis was carried out on five occasions during i week, when * This case was presented to the North of England Dermatological Society on 16 May 1978. 0007-0963/79/0700-0087 $02.00
V' 1979 British Association of Dermatologists
87
H.C.Huhhard and B.Portnoy
FIGURE I. Crusted erythematous rash on face of patient.
she was 15 weeks pregnant, with a total exchange of 9 1. Her most disabling feature at this stage was vasculitis of the fingers which improved dramatically after treatment, and she was discharged home a month earlier than in the previous pregnancy. A further exchange was carried out 3 weeks later but no further attempts were made because of poor veins. The patient had a normal baby by caesarean section, and is now maintained on 15 mg prednisolone a day. Investigations During her second pregnancy: ESR 75 mm/h; WBC 1600 m m ^ platelets I26,ooo;mm'; LE cells present; ANF positive 4- + ; a skin biopsy from the forearm showed the histological features of bullous lupus erythematosus, and immunofiuorescent studies showed IgG at the dermo-epidermal junction. During the third pregnancy while she was on high doses of systemic steroids: ANA i :2ooo homogenous IgG, anti DNA antibody 25 units, ml (< 10, normal). At all times serum complement, immunoglobulins, proteins, creatinine, WR, urine microscopy and chest X-rays have been normal: no immune complexes (Ciq) were found.
SLE treated with plasmapheresis
f^
DISCUSSION
Plasma exchange has been used successfully in rhesus disease, myasthenia gravis and renal disease as well as SUE {British Medical JotimaU 1978). Initially 1-5-3 1 are removed a day and replaced with fresh or dried plasma, or a plasma substitute; in pregnancy fresh plasma must be used. When the disease is controlled, maintenance exchanges are carried out at weekly to monthly intervals. Occasionally it is necessary to insert an arteriovenous shunt if the veins are very poor, and some centres use concurrent immunosuppressive drugs (Moran et al.^ 1977). Verrier Jones et a!. (1976) described eight patients with SLE, seven of whom had high anti-DNA antibodies and four had high levels of immune complexes; the latter group did well with plasmapheresis. Since then patients without immune complexes detectable by the methods used have benefited from plasmapheresis (Bacon, personal communication): the explanation for this is not clear, but it is possible that factors other than immune complexes are removed or that present techniques do not detect all of them. There are no complications from intensive plasmapheresis in pregnancy apart from slight nausea (Fraser et ai, 1976). A post mortem on the second baby showed a scabbed lesion 7 mm x 7 mm on the right arm at the site of a neonatal BCG vaccination, and the adrenals were small with fatty depletion. Although plasma immunoglobulins and cortisols were normal shortly after birth, it may be unwise to give these children BCG so early in life. This patient is also interesting because she subsequently became pregnant within a month of stopping azathioprine while she was on chloroquine and has had a normal baby. Plasmapheresis, although time consuming, expensive and cumbersome for routine use, can clearly play a useful part in the management of fulminating SLE, where there is a need to reduce the dose of oral steroids as in pregnancy, or where cytotoxic drugs are contraindicated because of pancytopenia or hypersensitivity. ACKNOWLEDGMENTS
We are very grateful to Dr Hull, Dr Stevens and Dr Vosylius of the Haematology Department for carrying out the plasmapheresis and to Dr Holt, Rheumatologist at the Manchester Royal Infirmary for helpful advice. REFERENCES BRirisH MEDICAL JOURNAL (1978) Plasmapheresis (leading article), i, loir. FRASER, I.D., BOTHAMLEY, J.E., BENNETT, M.O., AIRTH, G.R., LEHANE, D . , MCCARTHY, M . & ROBERTS, F . M .
(1976) Intensive antenatal plasmapheresis in severe rhesus isoimmunisation. Lancet, i, 6. MORAN, C.J., PARRY, H.F., MOWBRAY, J., RICHARDS, J . D . M . & GOLDSTONI-, A . H . (1977) Plasmapheresis in
Systemic Lupus Erythematosus. British Medical Journal, i, 1573. VERRIER JOKES, J., BUCNALL, R . C , CUMMING, R.H., ASI'LIN, C M . , FRASER, I.D., BOTHAMLEY, J., DAVIS, P. &
HAMBLIN, T.J. (1976) Plasmapheresis in the management of acute lupus erythematosus. Lancet, i, 709.
