Henoch-Schönlein purpura pathophysiology: Difference between revisions

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==Overview==
==Overview==
Henoch-Schönlein purpura (HSP) is an [[Immune-mediated disease|immune complex-mediated disease]] with circulating [[immune complexes]] and [[IgA|IgA rheumatoid factors]] usually follows [[Upper respiratory tract infection|upper respiratory tract infections]], various [[viruses]], and the [[bacteria]] have been implicated as triggers of the disease.


==Pathophysiology==
==Pathophysiology==
HSP can develop after infections with [[streptococcus|streptococci]] ([[Streptococcus pyogenes|β-haemolytic, Lancefield group A]]), [[hepatitis B]], [[herpes simplex virus]], [[parvovirus B19]], [[Coxsackievirus]], [[adenovirus]], ''[[Helicobacter pylori]]'', [[measles]], [[mumps]], [[rubella]], [[mycoplasma]] and numerous others. Drugs linked to HSP, usually as an idiosyncratic reaction, include [[vancomycin]], [[ranitidine]], [[streptokinase]], [[cefuroxime]], [[diclofenac]], [[enalapril]] and [[captopril]]. Several diseases have been reported to be associated with HSP, often without a causative link. Only in about 35% of cases can HSP be traced to any of these causes.
The pathophysiology of HSP:<ref name="pmid24424188">{{cite journal |vauthors=Yang YH, Yu HH, Chiang BL |title=The diagnosis and classification of Henoch-Schönlein purpura: an updated review |journal=Autoimmun Rev |volume=13 |issue=4-5 |pages=355–8 |date=2014 |pmid=24424188 |doi=10.1016/j.autrev.2014.01.031 |url=}}</ref><ref name="pmid24134307">{{cite journal |vauthors=Trnka P |title=Henoch-Schönlein purpura in children |journal=J Paediatr Child Health |volume=49 |issue=12 |pages=995–1003 |date=December 2013 |pmid=24134307 |doi=10.1111/jpc.12403 |url=}}</ref><ref name="pmid23684700">{{cite journal |vauthors=Rigante D, Castellazzi L, Bosco A, Esposito S |title=Is there a crossroad between infections, genetics, and Henoch-Schönlein purpura? |journal=Autoimmun Rev |volume=12 |issue=10 |pages=1016–21 |date=August 2013 |pmid=23684700 |doi=10.1016/j.autrev.2013.04.003 |url=}}</ref>
*HSP is a small vessel [[leukocytoclastic vasculitis]], but its [[pathophysiology]] is not completely understood.
*In patients with HSP the serum [[IgA]] levels are elevated, HSP is an [[immune complex]]-mediated disease with circulating [[immune complexes]] and IgA [[Rheumatoid factor|rheumatoid factors]] usually follows [[upper respiratory tract infections]], various viruses, and the [[bacteria]] have been implicated as triggers of the disease.
*Patients with HSP have circulating [[IgA]] [[Immune complexes|immune-complexes]], patients with HSPN have an additional large [[molecular]] mass [[IgA1]]-[[Immunoglobulin G|IgG]]-containing circulating [[immune complexes]].
*The [[IgA]]1 [[molecule]] has a hinge region containing up to six O-linked [[glycan]] chains consisting of [[N-acetylgalactosamine-4-sulfatase|N-acetylgalactosamine]], usually with an attached β1,3-linked [[galactose]].
*It has been reported that in patients with HSP, the activity of [[Galactosyltransferase|β1,3-galactosyltransferase]] in [[B cells|peripheral B cells]] is reduced, leading to a lack of terminal β1,3-galactosyl residues in the hinge region of IgA1.
*The primary defect leading to the production of such abnormally [[glycosylated]] IgA1 is probably heritable.
*These aberrantly [[glycosylated]] IgA1 [[molecules]] have been shown to form [[immune complexes]] with [[IgG]] [[antibodies]] specific for [[galactose]]-deficient [[IgA1]], thereby inhibiting the binding of the IgA [[Molecule|molecules]] to [[hepatic]] receptors and avoiding their internalization and [[degradation]] by [[Liver|hepatic cells]].
*This formation results in an increased amount of IgA [[immune complexes]] in [[circulation]].
*The complexes may then deposit in [[renal]] [[Mesangial cell|mesangial]] areas and activate the [[complement system]] by the alternative or [[lectin]] pathways, which play a major role in the [[pathophysiology]] of this disease.
*Further, after depositing in the mesangium, the [[galactose]]-deficient IgA1 [[immune complexes]] activate [[Mesangial cell|mesangial]] [[cells]].
*This results in the [[proliferation]] of cells such as macrophages and lymphocytes and the production of [[inflammatory]] and profibrogenic [[Cytokine|cytokines]] and [[chemokines]], which play a pivotal role in [[Mesangial cell|mesangial]] cell [[proliferation]], [[matrix]] expansion, and [[inflammatory]] cell [[Recruitment status|recruitment]].
*'''''Other mechanisms for developing HSP'''''
**[[Nephritis]]-associated [[plasmin]] [[receptor]], a [[Group A streptococcal infection|group A streptococcal antigen]], has been reported in some cases of HSP.
**Activation of the [[eosinophils]] and expression of the [[Smooth muscle|alpha-smooth muscle]] [[actin]] in the kidney also play a vital role in the [[pathogenesis]] of Henoch-Schönlein purpura.


The exact cause of HSP is unknown, but most of its features are due to the deposition of abnormal antibodies in the wall of blood vessels, leading to [[vasculitis]]. These antibodies are of the subclass IgA<sub>1</sub> in [[polymer]]s; it is uncertain whether the main cause is overproduction (in the digestive tract or the [[bone marrow]]) or decreased removal of abnormal IgA from the circulation. It is suspected that abnormalities in the IgA<sub>1</sub> molecule may provide an explanation for its abnormal behaviour in both HSP and the related condition [[IgA nephropathy]]. One of the  characteristics of IgA<sub>1</sub> (and [[IgD]]) is the presence of an 18 [[amino acid]]-long ''hinge region'' between [[complement system|complement]]-fixating region 1 and 2. Of the amino acids, half is [[proline]], while the other ones are mainly [[serine]] and [[threonine]]. The majority of the serines and the threonines have elaborate sugar chains, connected through [[oxygen]] atoms ([[glycosylation#O-linked glycosylation|O-glycosylation]]). This process is thought to stabilise the IgA molecule and make it less prone to [[proteolysis]]. The first sugar is always [[N-acetyl-galactosamine]] (GalNAc), followed by other [[galactose]]s and [[sialic acid]]. In HSP and IgAN, it appears that these sugar chains are deficient. The exact reason for these abnormalities are not known.
==Pathology==
Biopsy: <ref name="pmid9366584">{{cite journal |vauthors=Jennette JC, Falk RJ |title=Small-vessel vasculitis |journal=N. Engl. J. Med. |volume=337 |issue=21 |pages=1512–23 |date=November 1997 |pmid=9366584 |doi=10.1056/NEJM199711203372106 |url=}}</ref><ref name="pmid25557596">{{cite journal |vauthors=Chen JY, Mao JH |title=Henoch-Schönlein purpura nephritis in children: incidence, pathogenesis and management |journal=World J Pediatr |volume=11 |issue=1 |pages=29–34 |date=February 2015 |pmid=25557596 |doi=10.1007/s12519-014-0534-5 |url=}}</ref><ref name="pmid23842510">{{cite journal |vauthors=Kawasaki Y, Ono A, Ohara S, Suzuki Y, Suyama K, Suzuki J, Hosoya M |title=Henoch-Schönlein purpura nephritis in childhood: pathogenesis, prognostic factors and treatment |journal=Fukushima J Med Sci |volume=59 |issue=1 |pages=15–26 |date=2013 |pmid=23842510 |doi= |url=}}</ref>
*'''Indications'''
**No rash
**[[Abnormal]] [[renal function tests]]
 
'''Skin biopsy'''
*Light Microscopy
**[[IgA]] [[Deposition (physics)|deposition]] in postcapillary [[venules]] with [[IgA]] [[Deposition (chemistry)|deposition]] and [[leukocytoclastic vasculitis]] in is a [[pathognomonic]] microscopic feature of Henoch-Schönlein Purpura.
**Skin lesions less than 24 hrs are preferred as the chronic lesion lack the [[immunoglobulin]] isotypes essential for the diagnosis of HSP.
**A biopsy from a different skin site is taken for the [[immunofluorescent]] studies to confirm the [[diagnosis]].
 
'''Renal biopsy'''
*[[IgA]] [[Deposition (physics)|deposition]] in the [[mesangium]] on [[immunofluorescence]] microscopy should be differentiated from the [[IgA]] [[nephropathy]].  
*Light microscopic features range from isolated [[Mesangial cell|mesangial]] [[proliferation]] to severe [[Rapidly progressive glomerulonephritis|crescentic glomerulonephritis]].


==References==
==References==


{{reflist|2}}
{{reflist|2}}
[[Category:Disease]]
[[Category:Rheumatology]]
[[Category:Pediatrics]]
[[Category:Nephrology]]
[[Category:Autoimmune diseases]]
[[Category:Hematology]]
[[Category:Mature chapter]]


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Latest revision as of 16:05, 5 February 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Henoch-Schönlein purpura (HSP) is an immune complex-mediated disease with circulating immune complexes and IgA rheumatoid factors usually follows upper respiratory tract infections, various viruses, and the bacteria have been implicated as triggers of the disease.

Pathophysiology

The pathophysiology of HSP:[1][2][3]

Pathology

Biopsy: [4][5][6]

Skin biopsy

Renal biopsy

References

  1. Yang YH, Yu HH, Chiang BL (2014). "The diagnosis and classification of Henoch-Schönlein purpura: an updated review". Autoimmun Rev. 13 (4–5): 355–8. doi:10.1016/j.autrev.2014.01.031. PMID 24424188.
  2. Trnka P (December 2013). "Henoch-Schönlein purpura in children". J Paediatr Child Health. 49 (12): 995–1003. doi:10.1111/jpc.12403. PMID 24134307.
  3. Rigante D, Castellazzi L, Bosco A, Esposito S (August 2013). "Is there a crossroad between infections, genetics, and Henoch-Schönlein purpura?". Autoimmun Rev. 12 (10): 1016–21. doi:10.1016/j.autrev.2013.04.003. PMID 23684700.
  4. Jennette JC, Falk RJ (November 1997). "Small-vessel vasculitis". N. Engl. J. Med. 337 (21): 1512–23. doi:10.1056/NEJM199711203372106. PMID 9366584.
  5. Chen JY, Mao JH (February 2015). "Henoch-Schönlein purpura nephritis in children: incidence, pathogenesis and management". World J Pediatr. 11 (1): 29–34. doi:10.1007/s12519-014-0534-5. PMID 25557596.
  6. Kawasaki Y, Ono A, Ohara S, Suzuki Y, Suyama K, Suzuki J, Hosoya M (2013). "Henoch-Schönlein purpura nephritis in childhood: pathogenesis, prognostic factors and treatment". Fukushima J Med Sci. 59 (1): 15–26. PMID 23842510.

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