TREATMENT OF HENOCH-SCHONLEIN PURPURA : WHAT DO WE KNOW,

WHAT DO WE NEED ?

Eric THERVET, MD, PhD

Service de Néphrologie et Transplantation Rénale

Hôpital Saint-Louis

1, avenue Claude Vellefaux

75010 Paris, France

e-mail : eric.thervet@sls.ap-hop-paris.fr

Henoch-Schönlein purpura (HSP) is a leucocytoclastic vasculitis involving small vessels with

the deposition of immune complexes containing immunoglobulin A (IgA). It is characterized

by the association of skin, joint and gastrointestinal manifestations which may occur in

successive episodes (1). In addition to these manifestations, renal involvement is common,

and the long-term prognosis depends on its severity.

HSP primarily affects children and its incidence is around 15 cases/100,000 children/year (2).

It is less common in adults, approximatively 0.8 cases/100,000 adults/year. Although HSP has

been extensively studied in children, much less is known about its natural history in adults.

Even though the prognosis is considered to be good, some severe forms can exist.

During the initial presentation, gastrointestinal, cardiac, pulmonary, neurological and ocular

manifestations can be severe. However, the most important visceral manifestation is renal

because of its short and long-term implications.

The incidence of adult visceral involvement is variable. Severe gastro-intestinal bleeding has

been reported in up to 40 % responsible for bloody diarrhea. Other complications such as

acute pancreatitis, enteropathy and colonic perforations can be observed. A cardiac

involvement can be observed in 3,8 % of patients with pericarditis or myocardial infarct.

Clinical pulmonary involvement is present in only 2 % of patients. However, the involvement

is more frequent when looked systematically using CT scan or functional pulmonary test.

Neurological involvement, in 1 % of patients, is responsible for cephalagia secondary to

cerebral vasculitis or rare cerebral hemorraghe or infarct.

Renal involvement varies from 45 to 85% of cases, depending on the data for patients and of

renal involvement definition (3). Among the cases of glomerulonephritis, HSP is only

responsible for 0.6 to 2% of adults nephropathies (3, 4, 5). The risk of progression to renal

insufficiency, 15% (6, 7, 8) in children, seems to be higher when a long follow-up is possible

(9) or in adults, in more than 30% (10).

We analyzed retrospectively 250 adults suffering from HSP, with biopsy proven renal

involvement. Evidence of renal involvement was detected within a median period of 2

months after onset of the first clinical symptoms. Hypertension was frequent. Hematuria was

present in more than 90% of patients such as proteinuria with nephritic syndrom in 30 % of

patients. The most frequent lesion in renal biopsies was proliferative endocapillary

glomerulonephritis with possible extracapillary glomerulonephritis was only present in 8%

(Figure 1). In this study, mortality rate was 26%. The most frequent cause of death was

neoplasia (27% of deaths) not related to immunosuppressive treatment. The second cause of

death was infection (16%), two third being attributable to immunosuppressive treatment.

Death was secondary to HSP evolution in 11%, due, in particular, to severe digestive

involvement. Regarding renal survival, 11% of patients developed end stage renal failure,

13% had severe renal failure, and 14%, moderate renal insufficiency (Figure 2). It is clear

from our experience and others that long-term prognosis of HS purpura may be more severe

than once described.

However, there is no consensus or randomized study existing to give guidelines regarding

treatment.

Prognostic factors for severe renal impairment are the following. Clinical presentation,

including purpura, arthritis and abdominal involvement, was not associated with a significant

difference in renal function at the end of the follow up. Age over 50 years, the presence of

renal failure at onset, proteinuria >1g/l and the presence of macroscopic hematuria, were

strong predictors of severe renal failure. On renal biopsy, the glomerular classification, the

number of global sclerotic glomeruli and the degree of interstitial fibrosis were also predictive

of the renal outcome.

As to the efficacy of specific treatments, the results of pediatric therapeutic studies (11-13),

even though none was prospective and randomized against placebo, were mostly positive. In

adults, it is difficult to draw any conclusions from our study since their administration was

frequently associated with both clinical and histologic risk factors for renal failure (Figure 3).

On univariate analysis, steroids even seem to worsen the course of renal evolution. As in most

previous retrospective studies of HSP nephropathy, the limitation of the present investigation

was that the distribution of established renal risk factors was different in treated or not treated

patients.

We recently initiated a large multicentric, randomised, prospective study to evaluate the efficacy and safety of steroid treatment, either alone or combined with cyclophosphamide in severe forms of Henoch-Schönlein purpura

in adults (14, 15). This study will include patients with severe visceral involvement of HS

purpura in adults including all the clinical forms described in the beginning of this

manuscript. The primary end-point will be the control of the clinical acute disorder evaluated

by the Birmingham Vasculitis Activity Score. The secondary end-points will be the presence

of chronic damage including chronic renal failure. The results are awaited for the end of 2007.

Figure 1 : Extracapillary glomerulonephritis in a HS pupura nephropathy with focal

necorsis

Figure 2 : (A) Estimated Kaplan-Meier survival time after diagnosis of Henoch-Schönlein

purpura (HSP) and its 95% confidence interval (CI): median, 178 mo (95% CI, 157 mo to not

determined). (B) Estimated Kaplan-Meier time to occurrence of end-stage renal failure

(ESRF) after diagnosis of HSP and its 95% (CI): median, 246 mo (95% CI, 189 mo to not

determined). Analysis is somewhat hampered by the limited numbers of patients after 180 mo.

Figure 3 : Number of patients with severe renal failure at the end of follow-up, according

to their glomerular classification (classes 1, 2, 3a, 3b, 4, and 5) and the treatment received. n =

250 patients with Schönlein-Henoch nephritis. , no treatment; , corticosteroids alone; ,

corticosteroids + cyclophosphamide.

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