Favourable progression of acquired hemophilia-associated bullous pemphigoid

ARTICLE

Auteur(s) : Anne Caudron¹, Denis Chatelain², Olivia Christophe¹, Catherine Lok¹, Bertrand Roussel³, Valérie Viseux¹

¹Amiens University Medical Centre, South Hospital Dermatology Unit, F-80054 Amiens cedex 1, France
²Pathology Service, Amiens University Medical Centre
³Biological Hematology Service, Amiens University Medical Centre

In bullous pemphigoid (BP), an association with acquired hemophilia A (AHA) has been only rarely described. We report a regression of AHA following topical treatment of BP with clobetasol propionate alone.

A 68-year-old woman was hospitalized for BP (80 bullae on the first day with some hemorrhagic bullae), diagnosed on clinical, histological signs, anti-basement membrane antibodies (1/640, threshold 1/20) and anti-BPAG2 antibodies (182 AU.mL^-1, threshold 9 AU.mL^-1) in ELISA. Spontaneous lengthening of the Activated Partial Thromboplastin Time (APTT) (50 seconds, N = 24-34 seconds) was detected, not corrected by the addition of normal plasma. Prothrombin Time (PT) was normal. APTT coagulation factor assay (factors VIII, IX, XI, XII) revealed a low level of factor VIII (6%, N = 60-150%). The factor VIII inhibitor assay was 1.4 Bethesda, confirming the presence of acquired factor VIII inhibitor.

An external jugular vein catheterization was inserted before the AHA diagnosis. Given the severe bleeding after catheterization, 5000 IU of FEIBA^® (an activated prothrombic complex concentrate factors II-VII-IX-X) was administered.

BP was treated with topical administration of clobetasol propionate (40 g per day). After a month, we noted fewer than 10 bullae, APTT normalized (26 seconds for the patient plasma/29 seconds for the normal plasma), the factor VIII level climbed back up to 166%, and we could no longer detect anti-factor VIII antibodies. Anti-basement membrane antibody assay yielded a value of 1/80. Anti-BPAG2 antibodies were at 129 AU.mL^-1. A serum clobetasol assay was negative. The cortisol level was low, at 4.4 μg.dL^-1 (N = 7-28 μg.dL^-1). Three months later, no cutaneous recurrence of PB was observed, the patient was being treated with the same quantity of clobetasol. The coagulation profile was normal. Clobetasol propionate was progressively decreased. Five months after the initial abnormal cortisol level, it became normal.

Bullous diseases are rarely associated with AHA. Ten cases of BP associated with AHA, 5 of pemphigus vulgaris, 3 of acquired epidermolysis bullosa, one of cicatricial pemphigoid, have been published. Hemorrhage was present in 87% of cases [1]. The mortality has been estimated at 22% [1]. For the patients suffering from BP (table 1), hemorrhaging led to a diagnosis of AHA. In our case, there was no major hemorrhagic accident. Spontaneous lengthening of the APTT [2] led us to assay for factors VIII, IX, XI and XII. We decided to treat the patient with local clobetasol propionate [3]. The injection of FEIBA^® short-circuited the factor VIII activity but did not interfere with factor VIII levels or its auto-antibody.

Three hypotheses may be discussed to explain the disparition of AHA without systemic immunosuppressive agents:

• – For some authors, sequence homology between the factor VIII and the BPAG2 collagen XVII domain are present. The serum anti-factor VIII antibody may interact with the central collagen-like part of the BPAG2 protein [4, 5]. Resolution of BP due to a drop in anti-BPAG2 auto-antibodies may have induced a reduction of anti-factor VIII antibodies.
• – A second hypothesis concerns the immunosuppressive effects of topical corticoid use. After a month of daily clobetasol application, the cortisol level was low, suggesting a systemic effect of this treatment. As a systemic immunosuppressive drug, it could induce a decrease of the anti-VIII antibodies. However, we were unable to detect clobetasol in the blood using the techniques available in our laboratory. Once topical treatment was tailed off, cortisol levels were normal.
• – The last hypothesis relates to spontaneous regression of anti-factor VIII antibodies. Thirty per cent of acquired haemophilia cases resolve spontaneously, but rather concerning a non-autoimmune context [6]. Our case suggests that topical clobetasol may be sufficient to treat an AHA-associated BP.

Acknowledgements

References

2 Gupta S, Mahipal A. A case of acquired hemophilia associated with bullous pemphigoid. Am J Hematol 2007; 82: 502.

3 Soria A, Matichard E, Descamps V, Crickx B. Bullous pemphigoid and acquired hemophilia. Ann Dermatol Venereol 2007; 134: 353-6.

4 Patel RS, Harman KE, Nichols C, Burd RM, Pavord S. Acquired haemophilia heralded by bleeding into the oral mucosa in a patient with bullous pemphigoid, rheumatoid arthritis, and vitiligo. Postgrad Med J 2006; 82: e3.

5 Maczek C, Thoma-Uszynski S, Schuler G, Hertl M. Simultaneous onset of pemphigoid and factor VIII antibody hemophilia. Hautarzt 2002; 53: 412-5.

6 Lottenberg R, Kentro TB, Kitchens CS. Acquired hemophilia. A natural history study of 16 patients with factor VIII inhibitors receiving little or no therapy. Arch Intern Med 1987; 147: 1077-81.