CAMEO
PEMPHIGUS EOLIACEUS TREATED SUCCESSEULLY WITH PLASMA EXCHANGE CHRISTINA CINTIN, M.D., PREBEN JOFFE, M.D., S0REN D. LADEFOGED, M.D., ERIK DABELSTEEN, D.D.S., AND TORKIL MENNE, M.D.
A 64-year-old man had suffered from pemphigus foliaceus since 1979. The clinical diagnosis of pemphigus foliaceus was confirmed by histologic and immunologic examinations of a skin biopsy. Over the years he had several relapses despite treatment with steroids, erythromycin, gold, azathioprine, and cyclosporine. In 1989, the skin lesions became more severe even though prednisone and cyclophosphamide was increased (Fig. 1), and the patient developed severe side effects such as pneumonia, hypertension, heart failure, and noninsulin dependent diabetes mellitus. Serum titer of intercellular antibodies (ICAb) was 1:10,000 when plasma exchange was initiated. Four to 5 L were exchanged with albumin daily for 3 days. The skin symptoms disappeared, and the prednisone and the antihypertensive could be withdrawn. Six months later the patient had a full-blown relapse. Serum titer of ICAb was 1:2,500. Again treatment with highdose cyclophosphamide and prednisone was given, but without success; the patient developed severe side effects. Plasma exchanges were resumed and continued for 2.5 years with an interval of 6 weeks. The skin lesions rapidly improved. The serum level of ICAb decreased to 1:600. Prednisone was lowered to 7.5 mg/day and cyclophosphamide withdrawn. At present the patient is in remission and continues with plasma exchanges every second month.
DISCUSSION
Pemphigus foliaceus is an autoimmune skin disease, which primarily affects middle-aged people. There is strong evidence that intercellular antibodies (ICAb) directed against the 160 kD desmosomal glycoprotein of epidermal cell membranes (desmoglein) are directly responsible for producing the lesions. It has also been shown that pemphigus ICAb induced acantholysis after injection into monkey skin or oral epithelium.'-^ The current treatment of pemphigus foliaceus utilizes systemic steroids, immunosuppressants, or gold;
however, these treatments are not always able to control the disease and often cause severe side effects. Recently plasma exchange has been used successfully to treat other skin diseases believed to be caused by circulating autoantibodies.''^ High-dose adrenal steroid therapy provides adequate disease control in most patients with pemphigus foliaceus, but carries a significant risk of morbidity.'^ Immunosuppressive drugs may help to control the disease and provide a steroid-sparing effect, but since the pathogenic role of ICAb is well-known, plasma exchange may be a supplement to conventional therapy. Plasma exchange has been applied to other skin diseases with suspected autoimmune etiology, (e.g., bullous pemphigoid and pemphigus vulgaris).'''^ There is only one previous report of two patients suffering from pemphigus foliaceus, and they were both successfully treated with plasma exchange.^ In our patient, plasma exchange decreased the level of circulating ICAb and induced a decreased activity in the skin disease (Fig. 2). Some authors have found that the serum level of ICAb fluctuates with and reflects disease activity. This finding, however, has been challenged by others.'''''**'' Plasma exchange is a relatively safe procedure."' The tnost common side effects are thrombocytopenia, hypogammaglobulinemia, and depletion of complement ' components and clotting factors.'^''^ Furthermore, the procedure may increase the risk of systemic infections
From the Department of Nephrology, Herlev Hospital, University of Copenhagen, the School of Dentistry, University of Copenhagen, the Department of Dermatology, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark. Address for correspondence: Christina Cintin, M.D., Department of Nephrology B109, Herlev Hospital, Herlev Ringvej 75, 2730 Herlev, Denmark.
Figure 1. The patient before plasma exchange was initiated. 871
tntcrnational Journat of Dermatology Vot. 31, No. 12, December 1992
REEERENCES
S-titres of ICAb PEX3 10,000 .9,000 _ 8,000 _
1.
7,000-
2.
6,0005,000-
Relapse
4,0003,000 -
PE
3.
Roujeau JC, Morel P, Dalle E. Plasma exchange in bullous pemphigoid. Lancet 1984; i:486-489. 4. Cotterill JA, Barker DJ, Millard LG. Plasma exchange in the treatment of pemphigus vulgaris. Br J Dermatol 1978; 98:243. 5. Eular HH, Loffler H, Christopher Z. Synchronization of plasmapheresis and pulse cyclophosphamide therapy in pemphigus vulgaris. Arch Dermatol 1987; 123: 1205-1210. 6. Ahmed RA, Graham J, Jordon RE, et al. Pemphigus: current concepts. Ann Intern Med 1980; 92:396-405. 7. Roujeau J, Andre C, Eabre JM, et al. Plasma exchange in pemphigus. Arch Dermatol 1983; 119:215-221. 8. Judd KP, Lever WE. Correlation of antibodies in skin and serum with disease severity in pemphigus. Arch Dermatol 1979; 115:428-432. 9. Eine JD; Appel ML, Green L, Somes WH. Pemphigus vulgaris. Arch Dermatol 1988; 124:236-239. 10. Zieselman EM, Bongiovanni MB, Wurzel A. The complications of therapeutic plasma exchange. Vox Sang 1984; 46:270-276. 11. Lockwood CM, Rees AI, Pearsson TA, et al. Immunosuppression and plasma exchange in the treatment of Goodpasture's syndrome. Lancet 1976; i:711-713. 12. Domen RE, Kennedy MS, Jones LL, Stenhauer DA. Hemostatic imbalances produced by plasma exchange. Transfusion 1984; 24:336-339.
1
2,000 1,000 -
I
Hashimoto K, King LE, Yamanishi Y, et al. Identification of a substance binding pemphigus antihody and eoncanavalin A in the skin. J Invest Dermatol 1974; 62: 423-435. Russel WE, Stanely RJ. Human autoantihodies against a desmosomal protein complex with a calcium-sensitive epitope are characteristic of pemphigus foliaceus patients. J Exp Med 1987; 165:1719-1724.
I
I
I
,Time
6 12 18 24 32 months Figure 2. The serum titers of ICAb before and during plas7 ma exchange (PE).
in patients receiving immunosuppressive agents; however, our patient did not experience any side effects from plasma exchange.
CONCLUSIONS
Plasma exchange lowers circulating levels of ICAb. This may, therefore, be an alternative method of treating patients with pemphigus foliaceus who are unresponsive to, or suffer serious side effects from, conventional therapy. Acknowledgment: Sonia Phillips assisted in the preparation of the manuscript.
Theories About Scurvy I shall now, therefore, briefly state my experience of the scorbutic and antiscorbutic properties of the food usually supplied on long voyages, and the inferences I am led to deduce from it, and the generally received treatment of scurvy. To persons who are familiar with the treatment of scurvy only in print, it will seem strange when I assert, from extensive inquiry and practical experience, that few ships, even amongst the best regulated transports, pass through a voyage of more than four, or even three, consecutive months, without being visited by this loathsome pestilence. And the publicity of its presence in those instances of protracted voyages would be more generally known were the medical officers in charge not ashamed to admit such an occurrence, owing to the present popular belief that an outbreak of scurvy is impossible when strict attention is paid to cleanliness, ventilation, employment of the mind and body, and the free use of lime juice, and other supposed antiscorbutics. No doubt ennui, climatic changes, moisture, uncleanliness, impure air, &c., will predispose to scurvy, as they do to other diseases; but as to the generally supposed antiscorbutic properties of preserved milk, meats, vegetables, lime-juice such as we find in general use, and other specifics, I do not entertain the slightest belief. From Oliver WS. Scurvy: its cause. Lancet 1863; i:61. 872
PEMPHIGUS EOLIACEUS TREATED SUCCESSEULLY WITH PLASMA EXCHANGE CHRISTINA CINTIN, M.D., PREBEN JOFFE, M.D., S0REN D. LADEFOGED, M.D., ERIK DABELSTEEN, D.D.S., AND TORKIL MENNE, M.D.
A 64-year-old man had suffered from pemphigus foliaceus since 1979. The clinical diagnosis of pemphigus foliaceus was confirmed by histologic and immunologic examinations of a skin biopsy. Over the years he had several relapses despite treatment with steroids, erythromycin, gold, azathioprine, and cyclosporine. In 1989, the skin lesions became more severe even though prednisone and cyclophosphamide was increased (Fig. 1), and the patient developed severe side effects such as pneumonia, hypertension, heart failure, and noninsulin dependent diabetes mellitus. Serum titer of intercellular antibodies (ICAb) was 1:10,000 when plasma exchange was initiated. Four to 5 L were exchanged with albumin daily for 3 days. The skin symptoms disappeared, and the prednisone and the antihypertensive could be withdrawn. Six months later the patient had a full-blown relapse. Serum titer of ICAb was 1:2,500. Again treatment with highdose cyclophosphamide and prednisone was given, but without success; the patient developed severe side effects. Plasma exchanges were resumed and continued for 2.5 years with an interval of 6 weeks. The skin lesions rapidly improved. The serum level of ICAb decreased to 1:600. Prednisone was lowered to 7.5 mg/day and cyclophosphamide withdrawn. At present the patient is in remission and continues with plasma exchanges every second month.
DISCUSSION
Pemphigus foliaceus is an autoimmune skin disease, which primarily affects middle-aged people. There is strong evidence that intercellular antibodies (ICAb) directed against the 160 kD desmosomal glycoprotein of epidermal cell membranes (desmoglein) are directly responsible for producing the lesions. It has also been shown that pemphigus ICAb induced acantholysis after injection into monkey skin or oral epithelium.'-^ The current treatment of pemphigus foliaceus utilizes systemic steroids, immunosuppressants, or gold;
however, these treatments are not always able to control the disease and often cause severe side effects. Recently plasma exchange has been used successfully to treat other skin diseases believed to be caused by circulating autoantibodies.''^ High-dose adrenal steroid therapy provides adequate disease control in most patients with pemphigus foliaceus, but carries a significant risk of morbidity.'^ Immunosuppressive drugs may help to control the disease and provide a steroid-sparing effect, but since the pathogenic role of ICAb is well-known, plasma exchange may be a supplement to conventional therapy. Plasma exchange has been applied to other skin diseases with suspected autoimmune etiology, (e.g., bullous pemphigoid and pemphigus vulgaris).'''^ There is only one previous report of two patients suffering from pemphigus foliaceus, and they were both successfully treated with plasma exchange.^ In our patient, plasma exchange decreased the level of circulating ICAb and induced a decreased activity in the skin disease (Fig. 2). Some authors have found that the serum level of ICAb fluctuates with and reflects disease activity. This finding, however, has been challenged by others.'''''**'' Plasma exchange is a relatively safe procedure."' The tnost common side effects are thrombocytopenia, hypogammaglobulinemia, and depletion of complement ' components and clotting factors.'^''^ Furthermore, the procedure may increase the risk of systemic infections
From the Department of Nephrology, Herlev Hospital, University of Copenhagen, the School of Dentistry, University of Copenhagen, the Department of Dermatology, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark. Address for correspondence: Christina Cintin, M.D., Department of Nephrology B109, Herlev Hospital, Herlev Ringvej 75, 2730 Herlev, Denmark.
Figure 1. The patient before plasma exchange was initiated. 871
tntcrnational Journat of Dermatology Vot. 31, No. 12, December 1992
REEERENCES
S-titres of ICAb PEX3 10,000 .9,000 _ 8,000 _
1.
7,000-
2.
6,0005,000-
Relapse
4,0003,000 -
PE
3.
Roujeau JC, Morel P, Dalle E. Plasma exchange in bullous pemphigoid. Lancet 1984; i:486-489. 4. Cotterill JA, Barker DJ, Millard LG. Plasma exchange in the treatment of pemphigus vulgaris. Br J Dermatol 1978; 98:243. 5. Eular HH, Loffler H, Christopher Z. Synchronization of plasmapheresis and pulse cyclophosphamide therapy in pemphigus vulgaris. Arch Dermatol 1987; 123: 1205-1210. 6. Ahmed RA, Graham J, Jordon RE, et al. Pemphigus: current concepts. Ann Intern Med 1980; 92:396-405. 7. Roujeau J, Andre C, Eabre JM, et al. Plasma exchange in pemphigus. Arch Dermatol 1983; 119:215-221. 8. Judd KP, Lever WE. Correlation of antibodies in skin and serum with disease severity in pemphigus. Arch Dermatol 1979; 115:428-432. 9. Eine JD; Appel ML, Green L, Somes WH. Pemphigus vulgaris. Arch Dermatol 1988; 124:236-239. 10. Zieselman EM, Bongiovanni MB, Wurzel A. The complications of therapeutic plasma exchange. Vox Sang 1984; 46:270-276. 11. Lockwood CM, Rees AI, Pearsson TA, et al. Immunosuppression and plasma exchange in the treatment of Goodpasture's syndrome. Lancet 1976; i:711-713. 12. Domen RE, Kennedy MS, Jones LL, Stenhauer DA. Hemostatic imbalances produced by plasma exchange. Transfusion 1984; 24:336-339.
1
2,000 1,000 -
I
Hashimoto K, King LE, Yamanishi Y, et al. Identification of a substance binding pemphigus antihody and eoncanavalin A in the skin. J Invest Dermatol 1974; 62: 423-435. Russel WE, Stanely RJ. Human autoantihodies against a desmosomal protein complex with a calcium-sensitive epitope are characteristic of pemphigus foliaceus patients. J Exp Med 1987; 165:1719-1724.
I
I
I
,Time
6 12 18 24 32 months Figure 2. The serum titers of ICAb before and during plas7 ma exchange (PE).
in patients receiving immunosuppressive agents; however, our patient did not experience any side effects from plasma exchange.
CONCLUSIONS
Plasma exchange lowers circulating levels of ICAb. This may, therefore, be an alternative method of treating patients with pemphigus foliaceus who are unresponsive to, or suffer serious side effects from, conventional therapy. Acknowledgment: Sonia Phillips assisted in the preparation of the manuscript.
Theories About Scurvy I shall now, therefore, briefly state my experience of the scorbutic and antiscorbutic properties of the food usually supplied on long voyages, and the inferences I am led to deduce from it, and the generally received treatment of scurvy. To persons who are familiar with the treatment of scurvy only in print, it will seem strange when I assert, from extensive inquiry and practical experience, that few ships, even amongst the best regulated transports, pass through a voyage of more than four, or even three, consecutive months, without being visited by this loathsome pestilence. And the publicity of its presence in those instances of protracted voyages would be more generally known were the medical officers in charge not ashamed to admit such an occurrence, owing to the present popular belief that an outbreak of scurvy is impossible when strict attention is paid to cleanliness, ventilation, employment of the mind and body, and the free use of lime juice, and other supposed antiscorbutics. No doubt ennui, climatic changes, moisture, uncleanliness, impure air, &c., will predispose to scurvy, as they do to other diseases; but as to the generally supposed antiscorbutic properties of preserved milk, meats, vegetables, lime-juice such as we find in general use, and other specifics, I do not entertain the slightest belief. From Oliver WS. Scurvy: its cause. Lancet 1863; i:61. 872
