Severe glomerulonephritis and isolated ileitis in adult Henoch-Schönlein Purpura

Caterina Di Perna, Simona Vanni, Landino Allegri, Paolo Manganelli¹, Carlo Buzio

Dipartimento di Clinica Medica, Nefrologia e Scienze della Prevenzione, Università degli Studi di Parma, Italia

¹II Divisione Medica e Reumatologia, Azienda Ospedaliera di Parma, Italia
Key words: Henoch-Schönlein Purpura; hypersensitivity vasculitis; ileitis terminalis; levofloxacin; necrotizing, glomerulonephritis. Arthritis; IgA immune complex; immunosuppressive therapy; palpable purpura; pneumonia; quinolones

Introduction

Henoch-Schönlein Purpura (HSP) is a vasculitic syndrome involving small blood vessels, typical of children, but well described also in adults [1]. The classical clinical manifestations include a purpuric rash, arthritis, gastrointestinal involvement and nephritis, although other localizations such as nervous system, lungs and heart are occasionally reported [1].

In HSP, renal lesions, ranging from mild haematuria to end-stage renal disease, are well known [1], as well as gastrointestinal alterations, which are more frequently found in duodenum and colon, but which can also involve any portion of upper and lower digestive tract [2]. Documented gut alterations limited to the ileum, especially if associated with nephropathy, have been described in only a few reports, up to now [Table 1].

We describe a case of HSP in an adult patient with necrotizing glomerulonephritis with nephrotic syndrome concomitant to isolated ileal involvement.

Case report

A 56-year-old white man was admitted to our Department in November 1999 because of a highly suspicious clinical picture of HSP. In his past history he reported an episode of malarial fever at the age of 31 and blood hypertension lasting ten years, treated with enalapril (20 mg daily). His recent history began 6 weeks before, when he was admitted to the Pneumology Division of our Hospital for pyrexia, vomiting and diarrhoea. Chest X-ray showed a left basal density. He was diagnosed as having pneumonia of uncertain etiology (sputum and blood cultures were negative), and a therapy with levofloxacin (500 mg/day) and methylprednisolone (16 mg/day) per os was begun and prolonged for about 20 days obtaining a clinical and radiological recovery from pneumonia. The patient complained of polyarthralgias ten days after the withdrawal of therapy. A few days later he developed diffuse abdominal pain and severe diarrhoea, that sometimes was bloody. In addition a purpuric rash appeared on the legs, ankles and top of feet. For these reasons he came under our observation.

Physical examination revealed diffuse abdominal tenderness and arthritis signs at wrists, left elbow, right knee and ankles, as well as palpable purpura on the lower extremities, that were considerably edematous. The patient was afebrile. Laboratory data showed a red blood cell count of 4 x 10⁶/ml, a hemoglobin concentration of 12.2 g/dl and an increased blood leukocyte count (13.12 x 10³/ml). Platelets were 303 x 10³/ml. The Westergren erythrocyte sedimentation rate and the C-reactive protein were over the normal values (respectively 42 mm/1^sth and 110 mg/l). Serum total protein was seen as low as 4.1 g/dl  with serum albumin of 2 g/dl. The serum creatinine was 1.7 mg/dl and the glomerular filtration rate was 60 ml/min. Urine was sterile and there was proteinuria in the nephrotic range (5,580 mg per 24 h). Urinary sediment was telescopic, showing a large number of white and red cells, granular casts and 7-8 cellular casts per high-power field. Serum IgA were at the upper limit of the normal range (393 mg/dl), while levels of IgG and IgM were lower than normal (respectively 605 and 25 mg/dl). C3c and C4 complement components were normal. Cryoglobulins, as well as autoantibodies (rheumatoid factor, antinuclear antibodies, anti-double stranded DNA, and anti-neutrophil cytoplasmic antibodies) and Helicobacter Pylori antibodies were negative. Stool cultures were negative for pathogens including Yersinia Enterocolitica. Chest X-ray showed a slight bilateral basal density confirmed by chest computed tomography as fibrotic streaks. Ileocolonoscopy discovered no abnormalities in the colorectum, but showed a hemorrhagic, ulcerating mucosa with marked edema in the terminal ileum. Histological features of ileal specimens revealed a leukocytoclastic vasculitis [Figure 1]. Upper endoscopy evidenced hiatal hernia but no mucosal lesions were seen in the stomach and duodenum. Biopsy of a leg skin lesion revealed dermal capillaritis on histological examination and linear speckled IgA deposits in the basal membrane and in the dermal vessels on immunofluorescence microscopy. Renal biopsy was performed; light microscopy showed segmental mesangial proliferation, fibrinoid necrosis and polymorphonuclear granulocytes infiltration with nuclear dust in the glomeruli; moreover some glomerular crescents, interstitial inflammatory infiltrates and fibrosis were seen [Figure 2]. Immunofluorescence documented diffuse mesangial and loop IgA deposition [Figure 3].

In December 1999, a therapy was started with 500 mg/day intravenous methylprednisolone for three days and then with 1 mg/kg/day oral prednisone. Cyclophosphamide was added, initially intravenously 200 mg for three days, then orally at the dose of 2 mg/kg/day. Skin lesions, arthralgias and gastrointestinal symptoms reversed within a few days, but both proteinuria and edema at lower extremities were irrespective of therapy. At last observation, in March 2000, nephrotic syndrome persisted unchanged.

Discussion

HSP is a vasculitis whose pathogenetic mechanism is a hypersensitivity reaction against endogenous and exogenous stimuli, mediated by A immunoglobulins. Both increased IgA synthesis and diminished clearance have been implicated in the pathogenesis of IgA immune complex formation. This phenomenon occurs mainly in dermal, gastrointestinal and glomerular capillaries, relating to clinical manifestations [1].

The patient described in the present report showed the classical symptoms of HSP, with involvement of the skin, joints, gut and kidney [1]. The particular feature of this case is the severity of glomerulonephritis associated with isolated ileal involvement.

A recent review of the literature shows that renal involvement occurs in about 33% of children and 63% of adults with HSP [7]. The nephropathy is not only more common but also more severe in adults; renal outcome in HSP is conditioned by several factors, such as old age, nephrotic and/or acute nephritic syndrome at onset and a severe histological picture [7, 8]. Our patient, an adult with nephrotic syndrome at first appearance, in whom a proliferative diffuse necrotizing glomerulonephritis was documented, had no benefits from the immunosuppressive therapy. This lack of response is witness to the difficulty of obtaining good results in severe adult HSP glomerulonephritis. The literature does not provide a standardized treatment for HSP nephritis; pulse steroids, whether associated or not with immunosuppressive drugs, seem to get the best results, but other therapeutic strategies have been tried (plasmapheresis and immunoglobulins), in an attempt to obtain an improvement also for those patients who do not respond to steroids [1].

Gastrointestinal involvement is present in about 64% and 57% respectively of children and adults suffering from HSP [8]. Any portion of upper and lower gastrointestinal tract may be involved; even if the localization of HSP in the ileum is well known, more common sites are represented by duodenum and colon [2]. Usually, HSP enteropathy is self-limiting, but steroids can relieve a severe symptomatology and hasten the recovery. Nevertheless, some cases have been reported that failed to improve even with steroids [5]. Our patient, in whom intestinal involvement was limited to the ileum, had important abdominal symptoms, that however showed a quick improvement.

The etiology of HSP remains unknown, but various antigenic stimuli have been implicated in triggering this pathology, including a broad spectrum of infectious agents (especially of upper airways), allergens such as drugs, foods, insect bites and antigens associated with malignancies or autoimmune diseases [1]. Among drugs, various medications have been suggested as etiological factors, and there is some evidence that ciprofloxacin may occasionally induce HSP [9]. In our case the onset of HSP was seen after a pneumonia episode treated with levofloxacin. No data are available up to now about the relationship between HSP and levofloxacin, that anyhow belongs to the same class of drugs as ciprofloxacin.

In conclusion, we describe a case of adult HSP, presented after a pneumonia episode treated with levofloxacin, showing poor responding necrotizing glomerulonephritis and isolated ileitis. An etiological role of levofloxacin in HSP is attractive, but has still to be proved. The pathogenetic mechanisms underlying intestinal involvement of HSP limited to the ileum remain unexplained so far.

Acknowledgments