|Year : 2021 | Volume
| Issue : 1 | Page : 33-35
Delayed presentation with henoch–schönlein purpura in a patient with immunoglobulin a nephropathy
WA Lasanthi Kumari Weerasooriya1, Neelakanthi V I. Ratnatunga2, Dinesh Rangana1, Shenal Thalgahagoda1
1 Department of Paediatrics, Faculty of Medicine, University of Peradeniya, Kandy, Sri Lanka
2 Department of Pathology, Faculty of Medicine, University of Peradeniya, Kandy, Sri Lanka
|Date of Submission||04-Nov-2020|
|Date of Decision||20-Jun-2021|
|Date of Acceptance||14-Apr-2021|
|Date of Web Publication||30-Jun-2021|
Faculty of Medicine, University of Peradeniya, Kandy
Source of Support: None, Conflict of Interest: None
Henoch–Schönlein purpura (HSP) nephritis (HSPN) and immunoglobulin A (IgA) nephropathy (IgAN) are related conditions that may be encountered sequentially in the same patient, are described in twins, and have common biological and pathological basis. The clinical features as well as the spectrum of severity at presentation vary significantly among patients. Here, we report a girl who first presented with acute glomerulonephritis and biopsy evidence of acute diffuse proliferative IgA nephritis with crescents, and 5 years later, she developed HSP and proteinuria. Such delayed appearance of cutaneous manifestations after initial renal involvement is unusual, though reported previously. This presentation stresses the importance of long-term follow-up of patients with HSPN and primary IgAN.
Keywords: Crescentic glomerulonephritis, Henoch–Schönlein purpura, immunoglobulin A vasculitis nephropathy, proteinuria
|How to cite this article:|
Lasanthi Kumari Weerasooriya W A, I. Ratnatunga NV, Rangana D, Thalgahagoda S. Delayed presentation with henoch–schönlein purpura in a patient with immunoglobulin a nephropathy. Asian J Pediatr Nephrol 2021;4:33-5
|How to cite this URL:|
Lasanthi Kumari Weerasooriya W A, I. Ratnatunga NV, Rangana D, Thalgahagoda S. Delayed presentation with henoch–schönlein purpura in a patient with immunoglobulin a nephropathy. Asian J Pediatr Nephrol [serial online] 2021 [cited 2021 Jul 25];4:33-5. Available from: https://www.ajpn-online.org/text.asp?2021/4/1/33/320189
| Introduction|| |
Henoch–Schönlein purpura (HSP) nephritis (HSPN), now termed immunoglobulin A (IgA) vasculitis, is closely related in its pathogenesis to IgA nephropathy (IgAN) and is occasionally encountered sequentially in the same patient or in twins.,, The clinical picture and spectrum of severity at presentation varies widely between individual cases. We report a girl who initially presented with acute glomerulonephritis with biopsy evidence of acute diffuse proliferative IgA nephritis with crescent formation. Five years later, she developed cutaneous manifestations and proteinuria indicating IgA vasculitis. Such delayed appearance of cutaneous lesions, though described, is unusual.
| Case Report|| |
An 8-year-old girl, who was previously well, presented in 2014 with gross hematuria, generalized edema, and hypertension but with normal urine output. Urinalysis revealed hematuria and significant proteinuria (spot urine protein-to-creatinine ratio [UPCR] of 5.9 mg/mg). Serum creatinine was normal, albumin was 23 g/L, cholesterol was 7.6 mmol/L, and anti-streptolysin O (ASO) titer was not elevated. Antinuclear antibodies (ANAs) were negative and complement levels (C3 and C4) were within the normal range. Serum IgA levels were normal. Persistent proteinuria with active urine sediment, and normal complement and ASO levels, prompted kidney biopsy. While all 14 glomeruli showed mesangial hypercellularity and neutrophilic infiltration, one glomerulus each had a cellular crescent and segmental mesangial sclerosis [Figure 1]a. There was occasional double contouring of the glomerular basement membrane [Figure 1]b along with focal interstitial lymphocytes. Immunofluorescence revealed IgA immune complexes in the capillaries only, along with linear deposition of immunoglobulin G (IgG); immunoglobulin M (IgM) and C3 were negative. These findings indicated an acute diffuse proliferative glomerular nephritis driven by IgA immune deposits.
|Figure 1: Kidney biopsy at initial presentation Glomeruli show evidence of acute diffuse proliferative glomerular nephritis with (a) cellular crescent and segmental mesangial sclerosis, and (b) occasional double contouring of the glomerular basement membrane|
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With a diagnosis of acute glomerulonephritis due to IgAN with crescents, the patient was administered intravenous pulses of methylprednisolone followed by oral prednisone along with monthly intravenous cyclophosphamide pulses for six doses. In view of persisting subnephrotic range proteinuria, therapy with azathioprine was started after the sixth dose of cyclophosphamide and was associated with complete remission of proteinuria. However, subsequently, there was a loss to follow-up for over a year associated with noncompliance to therapy. The patient then presented in early 2020 with bilateral lower limb edema, ankle and knee joint arthritis, and palpable purpuric rash involving bilateral lower limbs and buttocks [Figure 2]. While serum creatinine was normal, serum albumin was 26 g/L and cholesterol was 8.57 mmol/L. Complement C3 and C4 levels were normal and ANA was nonreactive. Urinalysis revealed significant proteinuria (UPCR 4.2 mg/mg) and microscopic hematuria. Kidney biopsy showed eight glomeruli with mesangial hypercellularity, one cellular crescent, and two glomeruli with segmental necrosis [Figure 3]. There was no glomerulosclerosis; there were a few interstitial lymphocytes. Immunofluorescence indicated IgA deposits (3+ staining) in capillaries and mesangium, no IgG deposition, and fine granular C3 (1+) and focal segmental IgM (1+) in capillaries. There was nothing to indicate chronic lesions. Based on this presentation, the diagnosis of IgAN was revised to IgA vasculitis associated with HSP. Immunosuppression was advised to be restarted.
|Figure 3: Kidney biopsy 5 years later showed (a) mesangial hypercellularity and cellular crescent; and (b) glomeruli with segmental necrosis|
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| Discussion|| |
HSP is a small-vessel vasculitis mediated by IgA, seen mostly in children 3–10 years old. Approximately half of the cases occur before the age of 5 years. The condition is infrequently seen among adults, with an incidence of 0.1–1.2/million population older than 20 years. The typical clinical presentation of HSP includes a purpuric skin rash involving the extensor surfaces of the limbs and buttocks, abdominal pain, polyarthralgia or arthritis, and proteinuria with hematuria. The prevalence of renal involvement, based on serial urinalysis in unselected cohorts, ranges from 20% to 55%. The urinary abnormalities vary from isolated microscopic hematuria to nephrotic range proteinuria and rarely, rapidly progressive crescentic glomerulonephritis.
A relationship between primary IgAN and HSP is considered based on indistinguishable histopathology and shared pathogenesis. Both are IgA-mediated conditions triggered by mucosal infections and associated with mesangial deposition of IgA immune complexes. Abnormal glycosylation of this immunoglobulin is postulated to be the cause for this abnormal deposition. The IgA1 subclass is the predominant immunoglobulin deposited in the glomeruli in both the conditions. IgA is deposited in capillaries more in HSP than in IgAN, leading HSPN to be renamed as IgA vasculitis. Both the conditions have been reported to occur within families, suggesting a common genetic basis. Levy reported five patients with HSP in a cohort of 40 French families with IgAN. Patients with HSP also can have episodic macroscopic hematuria triggered by upper respiratory infections, following the initial presentation, akin to IgAN. In addition, extrarenal manifestations are reported in IgAN, similar to HSP. Epidemiological similarities also exist, with a predominance of boys in both the conditions and occurrence in the same geographic locations.
The cutaneous manifestations of HSP occur concurrently with renal involvement in the majority of patients with HSPN. However, skin lesions precede renal involvement in around 25% of cases and occur later than the renal manifestations in another 10% of patients. The appearance of cutaneous manifestations 5 years after initial renal involvement is however unusual, though delayed appearance has been reported previously., One reason for this extremely delayed occurrence in our patient could be the fact that she received prolonged immunosuppression owing to severe histological changes, including crescents, observed in the initial biopsy; this might have suppressed inflammation preventing the cutaneous manifestations from appearing until long after the cessation of therapy. The lack of mesangial IgA deposition in the initial biopsy might be attributed to delay in the biopsy, while the linear IgG deposition was considered related to heavy proteinuria.
In conclusion, this report emphasizes the importance of long-term follow-up of patients with both HSPN and primary IgAN, even when long-term remission has been achieved, as recurrences can occur in both the conditions. Cutaneous manifestations of HSP can follow renal involvement by a variable period of time.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient's parents have given their consent for patient's images and other clinical information to be reported in the journal. The patient's parents understand that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
We thank the parents of the girl described for allowing us to share her details and thank Ms.H.M.N.D. Herath, Technical Officer, Department of Pathology, University of Peradeniya, for technical assistance.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Ravelli A, Carnevale-Maffè G, Ruperto N, Ascari E, Martini A. IgA nephropathy and Henoch-Schönlein syndrome occurring in the same patient. Nephron 1996;72:111-2.
Knight JF. The rheumatic poison: A survey of some published investigations of the immunopathogenesis of Henoch-Schönlein purpura. Pediatr Nephrol 1990;4:533-41.
Davin JC, Weening JJ. Berger disease: Thirty years later. Eur J Pediatr 1999;158:437-43.
Trapani S, Micheli A, Grisolia F, Resti M, Chiappini E, Falcini F, et al
. Henoch Schonlein purpura in childhood: Epidemiological and clinical analysis of 150 cases over a 5-S period and review of literature. Semin Arthritis Rheum 2005;35:143-53.
Watts RA, Carruthers DM, Scott DG. Epidemiology of systemic vasculitis: Changing incidence or definition? Semin Arthritis Rheum 1995;25:28-34.
Wei LY, Liu C, Zhang YL, Li GL. IgA nephropathy with leucocytoclastic vasculitis. J Int Med Res 2018;46:3009-14.
Rieu P, Noël LH. Henoch-Schönlein nephritis in children and adults. Morphological features and clinicopathological correlations. Ann Med Interne (Paris) 1999;150:151-9.
Levy M. Familial cases of Berger's disease and anaphylactoid purpura. Kidney Int 2001;60:1611-2.
Davin JC, Ten Berge IJ, Weening JJ. What is the difference between IgA nephropathy and Henoch-Schönlein purpura nephritis? Kidney Int 2001;59:823-34.
Nakamoto Y, Asano Y, Dohi K, Fujioka M, Iida H, Kida H, et al
. Primary IgA glomerulonephritis and Schönlein-Henoch purpura nephritis: Clinicopathological and immunohistological characteristics. Q J Med 1978;47:495-516.
Coppo R, Amore A, Gianoglio B. Clinical features of Henoch-Schönlein purpura. Italian group of renal immunopathology. Ann Med Interne (Paris) 1999;150:143-50.
Hughes FJ, Wolfish NM, McLaine PN. Henoch-Schönlein syndrome and IgA nephropathy: A case report suggesting a common pathogenesis. Pediatr Nephrol 1988;2:389-92.
Kaneko K, Suzuki Y, Kiya K, Fukuda Y, Yabuta K. A case report suggesting a common pathogenesis for IgA nephropathy and Henoch-Schönlein purpura. Pediatr Nephrol 1994;8:750-1.
[Figure 1], [Figure 2], [Figure 3]