Chronic recalcitrant Henoch-Schönlein purpura: successful treatment with dapsone

ARTICLE

Auteur(s) : Thalia Papandreou¹, Matthias Dürken¹, Matthias Goebeler^2,3, Peter H Hoeger⁴, Sergij Goerdt², Wiebke K Peitsch²

¹Department of Pediatrics,
²Department of Dermatology, University Medical Centre Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68135 Mannheim, Germany
³Department of Dermatology, University Hospital Giessen, Giessen, Germany
⁴Department of Pediatric Dermatology, Catholic Children's Hospital Wilhelmstift, Hamburg, Germany

Henoch-Schönlein purpura (HSP) is a systemic IgA-mediated small vessel vasculitis characterized by palpable purpura, abdominal pain, renal involvement and arthritis. The course is usually self-limiting, however, one third of patients experience recurrence. A small percentage sustain severe complications such as nephritis with progression to end-stage renal disease, gastrointestinal, pulmonary or cerebrovascular haemorrhage [1].

Here we report a 13-year-old boy with a 7-year history of recurrent palpable purpura with microhematuria and abdominal pain. Initially the episodes were associated with upper respiratory tract infections and tonsillitis but over the last two years the patient had hardly been free of symptoms. A lesional skin biopsy showed leukocytoclastic vasculitis (figure 1A) without immunoglobulin or complement deposits in direct immunofluorescence. An extensive laboratory workup to exclude systemic ANCA- or connective tissue disease-associated vasculitis was unremarkable. Therefore, HSP was diagnosed despite lacking evidence of IgA deposits, according to the criteria of the American College of Rheumatology (for relevance of classification of immune complex vasculitis, see [2]). Flare-ups of the disease had repeatedly been treated with systemic corticosteroids (2 mg/kg prednisone), with an initial response but prompt relapse after tapering. Furthermore, therapy with intravenous immunoglobulins (2 g/kg, 2 cycles) had been without success.

When the patient presented to our department, physical examination revealed extensive palpable purpura on the upper and lower extremities (figures 1B, C) and urinalysis revealed mild proteinuria. Because of progressive arthralgia of both ankle joints, ongoing for one year, magnetic resonance imaging was performed, showing diffuse bone marrow oedema, possibly indicating vasculitic involvement of the bone marrow vessels. We decided to initiate treatment with dapsone, a bacteriostatic sulphonamide used for a variety of dermatological conditions associated with accumulation of neutrophils, including leukocytoclastic vasculitis. An initial combination of dapsone (1.2 mg/kg, 100 mg daily) with prednisone (2 mg/kg/day) led to prompt resolution of skin lesions, proteinuria, abdominal and joint pain, and glucocorticoids could rapidly be tapered. Dapsone was well tolerated apart from mild fatigue and minor methemoglobinemia (< 3%). MRI revealed a significant improvement of the bone marrow oedema. However, both attempts to discontinue dapsone and to reduce the daily dose from 100 to 50 mg resulted in relapses of the purpura, arthralgia and abdominal pain. The patient has now been asymptomatic on 100 mg/day dapsone for 15 months.

Treatment options for HSP include non-steroidal antiinflammatory drugs, pentoxifylline and H2 antihistamines for gastrointestinal involvement. Use of systemic steroids is a matter of controversy [1, 3]. According to recent meta analyses it seems rather unlikely that they anticipate or alter the course of renal involvement [3]. In cases with severe organ complications, other immunosuppressants such as azathioprine or cyclophosphamide, rituximab or intravenous immunoglobulins may be considered. However, their actual efficacy is often debatable and the risk-benefit ratio sometimes unfavourable. Moreover, successful treatment with dapsone has been reported, leading to marked improvement of cutaneous, articular and gastrointestinal symptoms [4, 5]. The largest pediatric case series included 8 patients, all of whom responded well to dapsone 1-2 mg/kg [5]. However, 6 of these relapsed after discontinuation, suggesting that dapsone allows control rather than cure of vasculitis. Its mechanism of action in leukocytoclastic vasculitis is unknown. Dapsone has been reported to act as an antioxidant and to suppress the generation of toxic free radicals by neutrophils and the production of prostaglandin D2. Furthermore, it inhibits the interactions between neutrophils and IgA [6]. Controlled trials of dapsone in HSP have not yet been performed. However, given its favourable safety profile, especially compared to corticosteroids and immunosuppressants, its value in HSP should be more widely appreciated.

Acknowledgements

References

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