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• the riddle of the association of alpha 1-antitrypsin deficiency, henoch-schonlein purpura, and ANCA
  oscar,m jolobe
  Published on: 23 March 2016

• Published on: 23 March 2016

  the riddle of the association of alpha 1-antitrypsin deficiency, henoch-schonlein purpura, and ANCA

  • oscar,m jolobe, retired geriatrician

  Although examples of interstitial lung disease such as diffuse alveolar haemorrhage and interstitial fibrosis were the only ones acknowledged to be associated with Henoch-Schonlein purpura(HSP) in a recent review(1), the association of HSP and pan-acinar emphysema attributable to alpha-1 antitrypsin(AAT) deficiency also deserves mention(2), especially in view of the speculative relationship between anti neutrophil cytosp...

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  Although examples of interstitial lung disease such as diffuse alveolar haemorrhage and interstitial fibrosis were the only ones acknowledged to be associated with Henoch-Schonlein purpura(HSP) in a recent review(1), the association of HSP and pan-acinar emphysema attributable to alpha-1 antitrypsin(AAT) deficiency also deserves mention(2), especially in view of the speculative relationship between anti neutrophil cytosplasmic antibodies(ANCA) and AAT deficiency, on the one hand(2), and ANCA vs HSP on the other(3)(4). Although the precise pathogenic basis of the association of AAT deficiency and the vasculitides is unclear, according to a recent evaluation a major role of alpha-1 antitrypsin(AAT) is to inhibit the destructive capabilities of proteinase-3(PR3), the serine protease released from neutrophils and monocytes at local sites of inflammation and tissue injury. Deficiency of AAT results in an increase in blood levels of free and active PR3 which, in turn generate further tissue injury and also generate an antibody response in the form of ANCA. ANCA, in turn, compounds PR3-related vascular injury by generating a cascade which includes activation of tumour necrosis factor(TNF)-primed neutrophils, accelaration of apoptosis of TNF-primed neutrophils, and secondary necrosis of the TNF-primed neutrophils themselves. The premature release of the toxic contents of the apoptopic cells is a further episode in the catalogue of ANCA-related tissue destruction.(2). In the clinical context a literature review revealed six cases of the association of AAT deficiency and HSP, one being a child aged 1.8 years when first reported, and the other five being adults aged 27-82. In the paediatric case there was no documentation of lung disease, and, in that instance, chronic renal disease was the significant complication of AAT deficiency. Among the five adults, four had documented pan-lobular emphysema, with co-existing chronic renal disease in three of those four. The one adult in whom pulmonary status had not been documented did also have chronic renal disease but the fourth adult with pan-lobular emphysema only experienced transient proteinuria and transient haematuria(2). In the latter instance, HSP was associated with ANCA of the Immunoglobulin G(IgG) subtype(5) whereas, among the three adults in whom pan-lobular emphysema co-existed with chronic renal disease, the one patient with ANCA was characterised by the IgA subtype of ANCA(2). In all, ANCA was present in only two of the 6 patients characterised by the association of AAT deficiency and HSP(2). Both had pan-lobular emphysema, but only one had chronic renal disease. ANCA of the IgA subclass was a feature of the patient with chronic renal disease(2), and ANCA of the IgG subclass charcterised the patient who was free of chronic renal disease(5). Although IgA ANCA has been identified in as many as 82.3% of 35 chidren aged 3-16 in the acute phase of HSP(3), among 28 consecutive adult HSP patients who presented predominantly with abdominal symptoms, the prevalence of ANCA(subtype not stated) was only 32.1%(4). In the former, no relationship was found between severity of HSP and IgA ANCA(3), but in the latter HSP patients with ANCA had significantly(p=0.02) higher clinical scores, significantly higher(p=0.01)serum creatinine levels, and significantly(p=0.03)higher 24 hour urinary protein excretion than their ANCA negative counterparts(4) However, given the variability in prevalence of ANCA in HSP patients free of AAT deficiency(3)(4), and the low prevalence of ANCA when HSP is associated with AAT(2), the role of ANCA, though speculative, nevertheless remains intriguing, especially in view of the theoretical considerations evaluated by Patterson et al(2). References (1) Tizard EJ., Hamilton-Ayres MJJ Henoch-Schonlein purpura Archives of Disease in Childhood 2008:93:1-8 (2)Patterson CC., Ross P., Pope-Harman AL., Knight DA., Magro CM Alpha-1 anti-trypsin deficiency and Henoch-Schonlein purpura associated with anti-neutrophil cytoplasmic and anti-endothelial cell antibodies of immunoglobulin-A isotype Journal of Cutaneous Pathology 2005:32:300-6 (3) Ozaltin F., Bakkaloglu A., Ozen S et al The significance of IgA class of antineutrophil cytoplasmic antibodies(ANCA) in childhood Henoch-Schonlein purpura Clinical Rheumatology 2004:23:426-9 (4) Zhang Y., Wu Y-K., Ciorba MA., Ouyang Q Significance of antineutrophil cytoplasmic antibody in adult patients with Henoch-Schonlein purpura presenting mainly with gastrointestinal symptoms World Journal of Gastroenterology 2008:14:622-6 (5) Meier P., Dayer E., Lemoine R., Blanc E Henoch-Schonlein purpura with IgG PR3-ANCA in a PiZZ alpha 1- antitrypsin deficient patient Nephrology Dialysis Transplantation 2001:16:1932-5

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  Conflict of Interest:
  None declared.

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