ARTICLE
In 1929 Bloom et al. were the first to report on the simultaneous
occurrence of psoriasis vulgaris and bullous pemphigoid [1]. Since then
more than 60 patients suffering from these both diseases have been described
in the literature. In all cases, the bullous pemphigoid developed after
the psoriasis. One therapeutical problem in these cases is that one standard
treatment of bullous pemphigoid, the oral administration of corticosteroids,
may lead to severe, even pustular psoriasis eruptions upon dose reductions.
In our case of bullous pemphigoid and psoriatic erythroderma, we were
successful in achieving a stable, complete remission of both conditions
using a combination treatment with azathioprine and acitretin.
Case report
A 59-year-old Caucasian male had suffered from severe psoriasis with
polyarthritis for 22 years and been topically treated with classical antipsoriatics
such as dithranol, tar and salicylic acid. For his additional chronic
psoriatic polyarthritis he had received gold therapy several years ago.
He was hospitalized several times in our hospital and received series
of UV-B radiation and PUVA therapy as well. In March 1996, his condition
worsened again and PUVA therapy was re-started with good initial success.
Furthermore, non-steroidal antiphlogistics and azulfidine were necessary
to treat his polyarthritis. Shortly after his stay on the ward and without
further consultation, the patient decided to discontinue this treatment.
Within 6 weeks the psoriasis worsened again. On admission we saw an almost
complete psoriatic erythroderma as well as tight blisters on both hands
and on the left leg (Fig. 1a,
b).
A biopsy specimen obtained from a psoriasis
lesion showed typical findings for psoriasis with hyperkeratotic acanthosis
and elongated rete ridges, subcorneal Munroe's microabscesses, and perivascular
lymphohistiocytic infiltrates in the upper dermis. A biopsy specimen obtained
from the border of a fresh bulla revealed subepidermal blistering with
eosinophil-rich inflammatory infiltrates at the bottom of the blister
and was typical for bullous pemphigoid (Fig.
2). Direct immunofluorescence from non-lesional skin revealed
IgG and C3 deposits along the basement membrane (Fig.
3). With the salt split skin technique, IgG deposits could be
demonstrated at the roof of the blister. Indirect immunofluorescence using
monkey esophagus as substrate disclosed basement membrane antibodies in
the patient serum at a titer of 1:256.
After this confirmation of a combination of
psoriasis and bullous pemphigoid, the patient was treated with acitretin
at an initial dose of 20 mg/day (0.3 mg/kg bodyweight). Dosage was increased
to 50 mg/day (0.8 mg/kg bodyweight) within two weeks. Additionally, treatment
with azathioprine at a dose of 100 mg/day (1.7 mg/kg bodyweight) was started.
External skin therapy consisted of daily applications of unspecific ointments
only. Under that regimen amelioration of skin redness and infiltration
was achieved and no new blisters occurred. After 3 weeks, an increase
of liver enzymes (alcalic phospatase 226 U/l, normal range 33-105 U/l,
and gamma-glutamyl-transferase 160 U/l, normal 6-28 U/l) occurred, which
normalised again upon reduction of the acitretin dose to 30 mg/day (0.5
mg/kg bodyweight). After 7 weeks of treatment, both the psoriasis and
the blisters were in complete remission. The psoriatic polyarthritis could
be easily controlled with the addition of ibuprofene (3 x 400 mg/day).
In an indirect immunofluorescence assay, performed 7 weeks after the start
of the treatment, serum titer of basement membrane antibodies decreased
to < 1:25. A follow up of 28 months revealed an occurrence of less
severe psoriatic lesions upon further reduction of the acitretin dosage
to 10 mg/day. Direct and indirect immunofluorescence at that time revealed
the presence of basement membrane antibodies in the skin and in the serum
(titer 1: 100). Psoriatic lesions immediately cleared again after an increase
of the acitretin dosis to 30 mg/day.
Discussion
Coexistence of psoriasis vulgaris and bullous pemphigoid has not infrequently
been reported so far [see Table
I for summary]. PUVA radiation is the most often discussed possible
triggering factor for the occurrence of the always secondary bullous autoimmune
disease. It was hypothezised that the antipsoriatic treatment (dithranol,
tar, UV-B-radiation, and especially PUVA) might increase the immunogenecity
of basement membrane proteins resulting in a higher risk of the formation
of autoantibodies [3]. In our patient, PUVA therapy was started shortly
prior to the occurrence of the bullous pemphigoid, again supporting this
close relationship.
Several therapeutic modalities have been described
for the treatment of coexisting psoriasis and bullous pemphigoid. Those
included the administration of methotrexate, dapsone, cyclosporine A [6,
11-14, 17] as well as erythromycin in combination with etretinate [25].
Systemic steroids should not be used [3] because of the risk of triggering
severe pustular psoriasis episodes upon dose modification. Therefore we
decided to treat our patient with a combination of acitretin, which is
well established in the treatment of severe psoriasis, and azathioprine,
often used as a combination agent to treat autoimmune bullous diseases.
This combination, to the best of our knowledge never tried before, was
highly successful in suppressing lesions of both diseases. A limited elevation
in liver enzymes at 50 mg/day acitretin and 150 mg azathioprine was the
only side-effect seen. Values returned to normal after reduction of the
acitretin dose to 30 mg/day. Our long term follow up showed that both
the clinical response and the good tolerability could be maintained at
lower doses. Again, no severe side effect has occurred in the follow up
so far. Our experience encourages further trials with this combination
treatment in patients suffering from psoriasis and bullous pemphigoid.
REFERENCES
1. Bloom D. Bullous eruption in a psoriatic patient. Arch Dermatol
1929; 20: 254-5.
2. Bork K. Psoriasis und bullöses Pemphigoid. Hautarzt 1987;
38: 348-51.
3. Kirtschig G, Chow ETY, Venning VA, Wojnarowska FT. Acquired subepidermal
bullous diseases associated with psoriasis: a clinical, immunopathological
and immunogenetic study. Br J Dermatol 1996; 135: 738-45.
4. Grattan CEH. Evidence of an association between bullous pemphigoid
and psoriasis. Br J Dermatol 1985; 113: 281-3.
5. Grunwald MH, David M, Feuerman EJ. Coexistence of psoriasis vulgaris
and bullous diseases. J Am Acad Dermatol 1985; 13: 224-8.
6. Koerber WA, Price NM, Watson W. Coexistent psoriasis and bullous
pemphigoid. Arch Dermatol 1978; 114: 1643-6.
7. Ahmed AR, Winkler NW. Psoriasis and bullous pemphigoid. Arch Dermatol
1977; 113: 845.
8. Simon M. Bullöses Pemphigoid bei Psoriasis vulgaris. Dermatol
im Bild 1991; 18: 23-5.
9. Stüttgen G, Bockendahl H, Remy W, Lewicki D. Psoriasis und bullöse
Dermatosen. Hautarzt 1978; 29: 134-40.
10. Wallach D, Cottenot F. Erythrodermic bullous pemphigoid or erythrodermic
psoriasis and bullous pemphigoid? J Am Acad Dermatol 1982; 7: 800.
11. Wollina U, Roth H. Psoriasis vulgaris partim inversa und bullöses
Pemphigoid. Dermatol Monschr 1987; 173: 29-32.
12. Albergo RP, Gilgor RS. Delayed onset of bullous pemphigoid after
PUVA and sunlight treatment of psoriasis. Cutis 1982; 30: 621-4.
13. Bianchi L, Gatti S, Nini G. Bullous pemphigoid and severe erythrodermic
psoriasis: combined low-dose treatment with cyclosporine and systemic
steroids. J Am Acad Dermatol 1992; 27: 278.
14. Boixeda JP, Soria C, Medina S, Ledo A. Bullous pemphigoid and psoriasis:
treatment with cyclosporine. J Am Acad Dermatol 1991; 24: 152.
15. Chen KR, Shimizu S, Miyakawa S, Ishiko A, Shimizu H, Hashimoto T.
Coexistence of psoriasis and unusual IgG- mediated subepidermal bullous
dermatosis: identification of a novel 200-kDa lower lamina lucida target
antigen. Br J Dermatol 1996; 134: 340-6.
16. Abel EA, Bennett A. Bullous pemphigoid. Arch Dermatol 1979;
115: 988-9.
17. Hisler BM, Blumenthal NC, Aronson PJ, Hashimoto K, Rudner EJ. Bullous
pemphigoid in psoriatic lesions. J Am Acad Dermatol 1989; 20: 683-4.
18. Kawahara Y, Hashimoto T, Ohata Y, Nishikawa T. Eleven cases of bullous
pemphigoid treated with a combination of minocycline and nicotinamide.
Eur J Dermatol 1996; 6: 427-9.
19. Person JR, Rogers RS. Bullous pemphigoid and psoriasis: does subclinical
bullous pemphigoid exist ? Br J Dermatol 1976; 95: 535-40.
20. Robinson JK, Baughman RD, Provost TT. Bullous pemphigoid induced
by PUVA therapy. Br J Dermatol 1978; 99: 709-13.
21. Saeki H, Nayashi N, Komine M, Soma Y, Shimada S, Watanabe K, Hashimoto
T. A case of generalized pustular psoriasis followed by bullous disease:
an atypical case of bullous pemphigoid or a novel bullous
disease ? Br J Dermatol 1996; 134: 152-5.
22. Tappeiner G, Konrad K, Holubar K. Erythrodermic bullous pemphigoid.
Am Acad Dermatol 1982; 6: 489-92.
23. Thomsen K, Schmidt H. PUVA-induced bullous pemphigoid. Br J Dermatol
1976; 95: 568-9.
24. Primka EJ, Camisa C. Psoriasis and bullous pemphigoid treated with
azathioprine. J Am Acad Dermatol 1998; 39: 121-3.
|
Printable version
