Henoch-Schonlein Purpura

Background

This is a variant of a leukocytoclastic vasculitis characterized by a purpuric rash occurring on the lower portion of the legs, usually in children and young adults. The rash varies from macular-papular to vesiculobullous with ulceration. Systemic symptoms include arthritis, abdominal pain, hematuria, cardiac, and neurologic changes. A preceeding upper respiratory infection is usually identified. Drugs such as penicillin, ampicillin, erythromycin, chlorpromazine, and acetylsalicylic acid may also precipitate the disease. Infections with Streptococcus and Helicobacter pylori gastritis have been implicated although many other bacteria and viruses have been implicated.

IgA immune complexes form and deposit within the skin and affected organs. This leads to complement activation and subsequent vascular damage. Patients usually recover although a small percentage of patients have persistent renal disease.

The histology is a leukocytoclastic vasculitis.

DISEASE ASSOCIATIONS CHARACTERIZATION

PARVOVIRUS B19

Parvovirus B19 and parvovirus V9 are not associated with Henoch-Schonlein purpura in children.

Heegaard ED, Taaning EB.

Department of Clinical Microbiology, University State Hospital, Rigshospitalet, Copenhagen, Denmark.

Pediatr Infect Dis J 2002 Jan;21(1):31-4 Abstract quote
BACKGROUND: Based on single case reports, parvovirus B19 (B19) has repeatedly been proposed as an etiologic agent in patients with Henoch-Schonlein purpura (HSP), perhaps causing vasculitis by direct invasion of vascular endothelial cells because of the tissue distribution of the cellular B19 receptor. A cohort of children with HSP and other vasculitic diseases was investigated and compared with healthy control children to assess the role of B19 as well as parvovirus V9 (a putative emerging B19-like virus).

PATIENTS AND METHODS: Serum samples from 36 children with HSP (n = 29) or other vasculitic diseases (n = 7) were examined, and 38 healthy bone marrow donors were used as controls. The presence of specific B19 and V9 IgM and IgG antibodies was determined with a recently developed enzyme-linked immunosorbent assay, and viral DNA was detected by a novel nested PCR.

RESULTS: Specific IgM was not present in any of the patient or control serum samples. B19 DNA was detected in one patient, a previously healthy 8-year-old boy diagnosed with HSP, whereas none of the controls was B19-positive. V9 was not detected in any of the clinical or control samples. It seems likely that B19 infection might have triggered the development of HSP in the B19-positive patient, because B19 viremia is otherwise uncommon.

CONCLUSIONS: Although causality is difficult to construe in single cases, the data indicate that B19 is not a common contributing factor in the pathogenesis of vasculitis and that this pathogen is only rarely associated temporally with HSP or vasculitic diseases in children.

Parvovirus B19 associated adult Henoch Schonlein purpura.

Cioc AM, Sedmak DD, Nuovo GJ, Dawood MR, Smart G, Magro CM.

Department of Pathology, Ohio State University, Columbus, OH, USA, Cadham Provincial Laboratories, Winnipeg, Manitoba, Canada.

J Cutan Pathol 2002 Nov;29(10):602-7 Abstract quote
BACKGROUND: Parvovirus B19 has recently been implicated in various vasculitic syndromes including Henoch Schonlein purpura (HSP), Wegener's granulomatosis and microscopic polyarteritis. The association was established through serology, the identification of DNA in the peripheral blood and affected tissues and more recently by RNA localization to cutaneous capillary endothelium. However, direct localization of the viral DNA to the glomerular and cutaneous endothelium in HSP in correlation with the histopathologic findings has not been demonstrated.

METHODS: Skin and kidney biopsy tissues were processed for hematoxylin and eosin, immunofluorescent, polymerase chain reaction (PCR) and reverse transcriptase in situ PCR studies.

CASE PRESENTATION: A 64-year-old-female presented with palpable purpura and nephrotic range proteinuria. Kidney and skin biopsies showed IgA-associated mesangioproliferative glomerulonephritis and IgA-associated leukocytoclastic vasculitis, respectively. A diagnosis of HSP was rendered. Her clinical course was refractory to prednisone. Parvovirus B19 DNA and tumor necrosis factor alpha DNA were identified in the dermal and glomerular capillary endothelial cells and surrounding dermal inflammatory cells.

CONCLUSION: This is the first documentation of B19 localization to dermal and glomerular capillary endothelium in HSP. It is important to recognize parvovirus B19-associated adult HSP cases, as the treatment of choice is intravenous gamma globulin in concert with anti-TNFalpha therapy. In contrast immunosuppressive therapy may lead to a persistent and/or worsening disease course.

HISTOLOGICAL TYPES CHARACTERIZATION

General

VARIANTS

KIDNEY

Grading of Acute and Chronic Renal Lesions in Henoch-Sch�nlein Purpura

Cheuk Chun Szeto, M.R.C.P., Paul C.L. Choi, F.R.C.P.A., Ka Fai To, F.R.C.P.A., Philip K.T. Li, F.R.C.P., Joannie Hui, F.R.A.C.P., Kai Ming Chow, M.R.C.P., C.B. Leung, M.R.C.P., Siu Fai Lui, F.R.C.P. and Fernand Mac-Moune Lai, F.R.C.P.A.

Department of Medicine and Therapeutics (CCSPKTL, KMC, CBL, SFL), Department of Anatomical and Cellular Pathology (PCLC, KFT, FM-ML), and Department of Pediatrics (JH), The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong Correspondence

Mod Pathol 2001;14:635-640 Abstract quote

The renal outcome of 34 patients with Henoch-Sch�nlein purpura nephritis was assessed clinically and by grading acute and chronic renal lesions using a system we applied to primary IgA nephropathy.

On a median follow-up period of 65 months, hypertension and the serum levels of creatinine and proteinuria at the time of renal biopsy were correlated with renal survival. Acute glomerular lesions including mesangial hypercellularity, endocapillary proliferation, necrosis, cellular crescents, and leukocytes infiltration were observed, respectively, in 41%, 12%, 50%, 29%, and 32% of the cases. Of these, only glomerular necrotizing lesion and cellular crescent were correlated with the renal survival. Chronic renal lesions based on a grading system applied to primary IgA nephropathy and assessing the extent of glomerular sclerosis (glomerular grading), of tubular loss and interstitial fibrosis (tubulointerstitial grading), and of hyaline arteriolosclerosis demonstrated correlation between these lesions, as well as with renal survival. On follow-up, these chronic renal lesions were predictors of subsequent clinical events associated with disease progression, such as impaired renal function, significant proteinuria, and development of hypertension.

Despite some limitations related to the relatively small size, this series indicates that distinction of acute and chronic lesions of Henoch-Schonlein purpura nephritis is important for both the prognosis and management of patients.

SKIN

Henoch-Schonlein purpura: clinicopathologic correlation of cutaneous vascular IgA deposits and the relationship to leukocytoclastic vasculitis.

Helander SD, De Castro FR, Gibson LE.

Department of Dermatology, Mayo Clinic, Rochester, Minnesota 55905, USA.

Acta Derm Venereol 1995 Mar;75(2):125-9 Abstract quote
Significant cutaneous vascular IgA deposits are common in Henoch-Schonlein purpura but not in other vasculitides. The specificity for IgA vascular deposits for Henoch-Schonlein purpura is not well defined.

To examine the specificity of IgA vascular deposits for this disease, we compared clinicopathologic features of 92 cases with IgA vascular deposits and a direct immunofluorescence impression of vasculitis with 90 similar cases without IgA deposits. Henoch-Schonlein purpura was diagnosed in 24% of cases with vascular IgA deposits on direct immunofluorescence examination. IgA deposits were frequent in erythema nodosum and venous stasis-related problems and in cryoglobulinemia, coagulopathic vasculopathies, and livedoid vasculitis.

Of our cases, 78% exhibited vascular fluorescence with multiple conjugates. No histologic or immunofluorescence pattern alone was specific. The diagnostic specificity for Henoch-Schonlein purpura is improved if gastrointestinal involvement, upper respiratory infection, or age < 20 years is present.

We propose diagnostic criteria for Henoch-Schonlein purpura incorporating clinical findings yielding sensitivity and specificity > 90%.

Immunoglobulin A-associated lymphocytic vasculopathy: a clinicopathologic study of eight patients.

Crowson AN, Magro CM, Usmani A, McNutt NS.

Central Medical Laboratories, Winnipeg, Manitoba, Canada, Department of Dermatology, University of Oklahoma, OH, USA, Regional Medical Laboratories, St John's Medical Center, Tulsa, OK, USA, Department of Pathology, Division of Dermatopathology, Ohio State University, Columbus, OH, USA, and Department of Pathology, Division of Dermatopathology, Weill Medical College of Cornell University, New York, NY, USA.

J Cutan Pathol 2002 Nov;29(10):596-601 Abstract quote
INTRODUCTION: Cutaneous IgA-associated vasculitis can be a clue to Henoch-Schonlein purpura (HSP), which typically comprises renal and gastrointestinal tract disease and arthritis, whereby prominent and predominant IgA deposits within the cutaneous vasculature provoke a pustular leukocytoclastic vasculitis.

DESIGN: We describe eight patients with a novel expression of a cutaneous IgA vascular injury syndrome, namely a lymphoid vasculopathy which clinically and light microscopically resembled a pigmentary purpura (PP) in six, and correlate direct immunofluorescence (DIF) and clinical features to light microscopy.

RESULTS: Among associated diseases were prior viral infection, an HSP symptom complex, an undifferentiated connective tissue disease syndrome, lupus erythematosus profundus (LEP), Degos' disease and Berger's disease. Skin lesions comprised non-palpable petechial lesions involving lower extremities in all cases and also the upper extremities in two. A superficial perivascular lymphocytic infiltrate unaccompanied by vascular fibrin deposits was associated with prominent erythrocyte extravasation including into the epidermis. Mural and extravascular fibrin deposition was seen in one biopsy from a PP-like lesion and mural fibrinoid necrosis was seen in the cases of LEP and Degos' disease; in biopsies from these three cases, the presence of fibrin deposition warranted use of the appellation 'lymphocytic vasculitis'. In all patients, DIF showed prominent and predominant IgA deposits.

CONCLUSIONS: A non-necrotizing lymphocytic purpuric vascular reaction is one manifestation of vascular IgA deposition in the skin. A subpopulation of human lymphocytes bear surface Fc receptor and/or C3 receptors ('complement receptor lymphocytes') which can bind circulating immune complexes (ICs) or C3 generated via activation of the alternative complement cascade. Thus, circulating ICs are a potential pathogenic basis of this eruption, the histologic differential diagnosis of which is idiopathic PP and PP of drug or viral etiology.

Rosai J. Ackerman's Surgical Pathology. Eight Edition. Mosby 1996.
Sternberg S. Diagnostic Surgical Pathology. Third Edition. Lipincott Williams and Wilkins 1999.
Robbins Pathologic Basis of Disease. Sixth Edition. WB Saunders 1999.

Commonly Used Terms

Leukocytoclastic vasculitis

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Last Updated 12/18/2002

DISEASE ASSOCIATIONS	CHARACTERIZATION
PARVOVIRUS B19
Parvovirus B19 and parvovirus V9 are not associated with Henoch-Schonlein purpura in children. Heegaard ED, Taaning EB. Department of Clinical Microbiology, University State Hospital, Rigshospitalet, Copenhagen, Denmark.	Pediatr Infect Dis J 2002 Jan;21(1):31-4 Abstract quote BACKGROUND: Based on single case reports, parvovirus B19 (B19) has repeatedly been proposed as an etiologic agent in patients with Henoch-Schonlein purpura (HSP), perhaps causing vasculitis by direct invasion of vascular endothelial cells because of the tissue distribution of the cellular B19 receptor. A cohort of children with HSP and other vasculitic diseases was investigated and compared with healthy control children to assess the role of B19 as well as parvovirus V9 (a putative emerging B19-like virus). PATIENTS AND METHODS: Serum samples from 36 children with HSP (n = 29) or other vasculitic diseases (n = 7) were examined, and 38 healthy bone marrow donors were used as controls. The presence of specific B19 and V9 IgM and IgG antibodies was determined with a recently developed enzyme-linked immunosorbent assay, and viral DNA was detected by a novel nested PCR. RESULTS: Specific IgM was not present in any of the patient or control serum samples. B19 DNA was detected in one patient, a previously healthy 8-year-old boy diagnosed with HSP, whereas none of the controls was B19-positive. V9 was not detected in any of the clinical or control samples. It seems likely that B19 infection might have triggered the development of HSP in the B19-positive patient, because B19 viremia is otherwise uncommon. CONCLUSIONS: Although causality is difficult to construe in single cases, the data indicate that B19 is not a common contributing factor in the pathogenesis of vasculitis and that this pathogen is only rarely associated temporally with HSP or vasculitic diseases in children.
Parvovirus B19 associated adult Henoch Schonlein purpura. Cioc AM, Sedmak DD, Nuovo GJ, Dawood MR, Smart G, Magro CM. Department of Pathology, Ohio State University, Columbus, OH, USA, Cadham Provincial Laboratories, Winnipeg, Manitoba, Canada.	J Cutan Pathol 2002 Nov;29(10):602-7 Abstract quote BACKGROUND: Parvovirus B19 has recently been implicated in various vasculitic syndromes including Henoch Schonlein purpura (HSP), Wegener's granulomatosis and microscopic polyarteritis. The association was established through serology, the identification of DNA in the peripheral blood and affected tissues and more recently by RNA localization to cutaneous capillary endothelium. However, direct localization of the viral DNA to the glomerular and cutaneous endothelium in HSP in correlation with the histopathologic findings has not been demonstrated. METHODS: Skin and kidney biopsy tissues were processed for hematoxylin and eosin, immunofluorescent, polymerase chain reaction (PCR) and reverse transcriptase in situ PCR studies. CASE PRESENTATION: A 64-year-old-female presented with palpable purpura and nephrotic range proteinuria. Kidney and skin biopsies showed IgA-associated mesangioproliferative glomerulonephritis and IgA-associated leukocytoclastic vasculitis, respectively. A diagnosis of HSP was rendered. Her clinical course was refractory to prednisone. Parvovirus B19 DNA and tumor necrosis factor alpha DNA were identified in the dermal and glomerular capillary endothelial cells and surrounding dermal inflammatory cells. CONCLUSION: This is the first documentation of B19 localization to dermal and glomerular capillary endothelium in HSP. It is important to recognize parvovirus B19-associated adult HSP cases, as the treatment of choice is intravenous gamma globulin in concert with anti-TNFalpha therapy. In contrast immunosuppressive therapy may lead to a persistent and/or worsening disease course.

HISTOLOGICAL TYPES	CHARACTERIZATION
General
VARIANTS
KIDNEY
Grading of Acute and Chronic Renal Lesions in Henoch-Sch�nlein Purpura Cheuk Chun Szeto, M.R.C.P., Paul C.L. Choi, F.R.C.P.A., Ka Fai To, F.R.C.P.A., Philip K.T. Li, F.R.C.P., Joannie Hui, F.R.A.C.P., Kai Ming Chow, M.R.C.P., C.B. Leung, M.R.C.P., Siu Fai Lui, F.R.C.P. and Fernand Mac-Moune Lai, F.R.C.P.A. Department of Medicine and Therapeutics (CCSPKTL, KMC, CBL, SFL), Department of Anatomical and Cellular Pathology (PCLC, KFT, FM-ML), and Department of Pediatrics (JH), The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong Correspondence	Mod Pathol 2001;14:635-640 Abstract quote The renal outcome of 34 patients with Henoch-Sch�nlein purpura nephritis was assessed clinically and by grading acute and chronic renal lesions using a system we applied to primary IgA nephropathy. On a median follow-up period of 65 months, hypertension and the serum levels of creatinine and proteinuria at the time of renal biopsy were correlated with renal survival. Acute glomerular lesions including mesangial hypercellularity, endocapillary proliferation, necrosis, cellular crescents, and leukocytes infiltration were observed, respectively, in 41%, 12%, 50%, 29%, and 32% of the cases. Of these, only glomerular necrotizing lesion and cellular crescent were correlated with the renal survival. Chronic renal lesions based on a grading system applied to primary IgA nephropathy and assessing the extent of glomerular sclerosis (glomerular grading), of tubular loss and interstitial fibrosis (tubulointerstitial grading), and of hyaline arteriolosclerosis demonstrated correlation between these lesions, as well as with renal survival. On follow-up, these chronic renal lesions were predictors of subsequent clinical events associated with disease progression, such as impaired renal function, significant proteinuria, and development of hypertension. Despite some limitations related to the relatively small size, this series indicates that distinction of acute and chronic lesions of Henoch-Schonlein purpura nephritis is important for both the prognosis and management of patients.
SKIN
Henoch-Schonlein purpura: clinicopathologic correlation of cutaneous vascular IgA deposits and the relationship to leukocytoclastic vasculitis. Helander SD, De Castro FR, Gibson LE. Department of Dermatology, Mayo Clinic, Rochester, Minnesota 55905, USA.	Acta Derm Venereol 1995 Mar;75(2):125-9 Abstract quote Significant cutaneous vascular IgA deposits are common in Henoch-Schonlein purpura but not in other vasculitides. The specificity for IgA vascular deposits for Henoch-Schonlein purpura is not well defined. To examine the specificity of IgA vascular deposits for this disease, we compared clinicopathologic features of 92 cases with IgA vascular deposits and a direct immunofluorescence impression of vasculitis with 90 similar cases without IgA deposits. Henoch-Schonlein purpura was diagnosed in 24% of cases with vascular IgA deposits on direct immunofluorescence examination. IgA deposits were frequent in erythema nodosum and venous stasis-related problems and in cryoglobulinemia, coagulopathic vasculopathies, and livedoid vasculitis. Of our cases, 78% exhibited vascular fluorescence with multiple conjugates. No histologic or immunofluorescence pattern alone was specific. The diagnostic specificity for Henoch-Schonlein purpura is improved if gastrointestinal involvement, upper respiratory infection, or age < 20 years is present. We propose diagnostic criteria for Henoch-Schonlein purpura incorporating clinical findings yielding sensitivity and specificity > 90%.
Immunoglobulin A-associated lymphocytic vasculopathy: a clinicopathologic study of eight patients. Crowson AN, Magro CM, Usmani A, McNutt NS. Central Medical Laboratories, Winnipeg, Manitoba, Canada, Department of Dermatology, University of Oklahoma, OH, USA, Regional Medical Laboratories, St John's Medical Center, Tulsa, OK, USA, Department of Pathology, Division of Dermatopathology, Ohio State University, Columbus, OH, USA, and Department of Pathology, Division of Dermatopathology, Weill Medical College of Cornell University, New York, NY, USA.	J Cutan Pathol 2002 Nov;29(10):596-601 Abstract quote INTRODUCTION: Cutaneous IgA-associated vasculitis can be a clue to Henoch-Schonlein purpura (HSP), which typically comprises renal and gastrointestinal tract disease and arthritis, whereby prominent and predominant IgA deposits within the cutaneous vasculature provoke a pustular leukocytoclastic vasculitis. DESIGN: We describe eight patients with a novel expression of a cutaneous IgA vascular injury syndrome, namely a lymphoid vasculopathy which clinically and light microscopically resembled a pigmentary purpura (PP) in six, and correlate direct immunofluorescence (DIF) and clinical features to light microscopy. RESULTS: Among associated diseases were prior viral infection, an HSP symptom complex, an undifferentiated connective tissue disease syndrome, lupus erythematosus profundus (LEP), Degos' disease and Berger's disease. Skin lesions comprised non-palpable petechial lesions involving lower extremities in all cases and also the upper extremities in two. A superficial perivascular lymphocytic infiltrate unaccompanied by vascular fibrin deposits was associated with prominent erythrocyte extravasation including into the epidermis. Mural and extravascular fibrin deposition was seen in one biopsy from a PP-like lesion and mural fibrinoid necrosis was seen in the cases of LEP and Degos' disease; in biopsies from these three cases, the presence of fibrin deposition warranted use of the appellation 'lymphocytic vasculitis'. In all patients, DIF showed prominent and predominant IgA deposits. CONCLUSIONS: A non-necrotizing lymphocytic purpuric vascular reaction is one manifestation of vascular IgA deposition in the skin. A subpopulation of human lymphocytes bear surface Fc receptor and/or C3 receptors ('complement receptor lymphocytes') which can bind circulating immune complexes (ICs) or C3 generated via activation of the alternative complement cascade. Thus, circulating ICs are a potential pathogenic basis of this eruption, the histologic differential diagnosis of which is idiopathic PP and PP of drug or viral etiology.