Henoch-Schönlein purpura
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2008-07-11T23:34:34Z
Betacommand
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replacing [[:Image:Purpura.JPG]] with [[:Image:Purpura2.JPG|commons copy]]
{{Infobox_Disease
| Name = Henoch-Schönlein purpura
| Image = purpura.jpg
| Caption = Typical purpura on lower leg
| DiseasesDB = 5705
| ICD10 = {{ICD10|D|69|0|d|65}}<br />([[ILDS]] D69.010)
| ICD9 = {{ICD9|287.0}}
| ICDO =
| OMIM =
| MedlinePlus = 000425
| eMedicineSubj = derm
| eMedicineTopic = 177
| eMedicine_mult = {{eMedicine2|emerg|767}} {{eMedicine2|emerg|845}} {{eMedicine2|ped|3020}}
| MeshID = D011695
}}
'''Henoch-Schönlein purpura''', also known as '''allergic purpura''' and commonly abbreviated to '''HSP''', is a systemic [[vasculitis]] (inflammation of blood vessels) characterized by deposition of [[immune complex]]es containing the antibody [[IgA]] in the [[skin]] and [[kidney]]. It occurs mainly in young children.
Typical symptoms include palpable [[purpura]] (small hemorrhages in the skin), [[arthralgia|joint pains]] and [[abdominal pain]]. Most cases are self-limiting and require no treatment apart from symptom control, but the disease may relapse in a third of the cases and cause irreversible kidney damage in about one in a hundred cases.<ref name=Saulsbury2001>{{cite journal |author=Saulsbury FT |title=Henoch-Schönlein purpura |journal=Curr Opin Rheumatol |volume=13 |issue=1 |pages=35–40 |year=2001 |pmid=11148713 |doi=10.1097/00002281-200101000-00006}}</ref> The exact cause of Henoch-Schönlein purpura is unknown, although it may occur after certain viral and bacterial infections, as well as an [[adverse drug reaction]] to some medications.
== Signs and symptoms ==
=== Presentation ===
[[Image:Purpura2.JPG|thumb|More severe case of HSP on child's foot, leg, and arm]]
[[Purpura]], [[arthritis]] and [[abdominal pain]] are known as the ''classic triad'' of Henoch-Schönlein purpura.<ref name=Kraft1998>{{cite journal |author=Kraft DM, Mckee D, Scott C |title=Henoch-Schönlein purpura: a review |journal=Am Fam Physician |volume=58 |issue=2 |pages=405–8, 411 |year=1998 |pmid=9713395 |url=http://www.aafp.org/afp/980800ap/kraft.html}}</ref> Purpura occur in all cases, joint pains and arthritis in 80%, and abdominal pain in 62%. Some include [[Gastrointestinal bleeding|gastrointestinal hemorrhage]] as a fourth criterion; this occurs in 33% of cases, sometimes but not necessarily due to [[Intussusception (medical disorder)|intussusception]]).<ref name=Saulsbury1999>{{cite journal |author=Saulsbury FT |title=Henoch-Schönlein purpura in children. Report of 100 patients and review of the literature |journal=Medicine (Baltimore) |volume=78 |issue=6 |pages=395–409 |year=1999 |pmid=10575422 |doi=10.1097/00005792-199911000-00005}}</ref> The purpura typically appear on the legs and buttocks, but may also be seen on the arms, face and trunk. The abdominal pain is colicky in character, and may be accompanied by nausea, vomiting, constipation or diarrhea. There may be blood or mucus in the stools.<ref>{{cite book |author=Fauci AS |editor=Braunwald E, Isselbacher KJ, Petersdorf RG, Wilson JD, Martin JB, Fauci AS|title=Harrison's Book of Internal Medicine |edition=11th|volume=2|year=1987|publisher=McGraw Hill|isbn=0-07-079454-5|pages=p. 1441 |chapter=269:The Vasculitis Syndromes}}</ref> The joints involved tend to be the [[ankle]]s, [[knee]]s, and [[elbow]]s but arthritis in the hands and feet is possible; the arthritis is non-erosive and hence causes no permanent deformity.<ref name=Kraft1998/> 40% have evidence of [[kidney]] involvement, mainly in the form of [[hematuria]] (blood in the urine), but only a quarter will have this in sufficient quantities to be noticeable without laboratory tests.<ref name=Saulsbury1999/> Problems in other organs, such as the [[central nervous system]] (brain and spinal cord) and [[lung]]s may occur, but much less commonly than the skin, bowel and kidneys.<ref name=Saulsbury2001/>
The disease tends to last about 4 weeks, and then resolves spontaneously.<ref name=Saulsbury2001/>
=== Kidney involvement ===
Of the 40% of patients who develop kidney involvement, almost all have evidence (visible or on [[urinalysis]]) of blood in the urine. More than half also have [[proteinuria]] (protein in the urine), which in one eighth is severe enough to cause [[nephrotic syndrome]] (generalised swelling due to low protein content of the blood). While abnormalities on urinalysis may continue for a long time, only 1% of all HSP patients develop [[chronic kidney disease]].<ref name=Saulsbury2001/> [[Hypertension]] (high blood pressure) may occur. Protein loss and high blood pressure, as well as the features on [[biopsy]] of the kidney if performed, may predict progression to advanced kidney disease. Adults are more likely than children to develop advanced kidney disease.<ref name=Saulsbury2001/><ref name=Shrestha2006>{{cite journal |author=Shrestha S, Sumingan N, Tan J, ''et al'' |title=Henoch Schönlein purpura with nephritis in adults: adverse prognostic indicators in a UK population |journal=QJM |volume=99 |issue=4 |pages=253–65 |year=2006 |pmid=16565522 |doi=10.1093/qjmed/hcl034| url=http://qjmed.oxfordjournals.org/cgi/content/full/99/4/253}}</ref>
== Diagnosis ==
[[Image:Henoch-Schönlein nephritis IgA immunostaining.jpg|thumb|[[Immunohistochemistry|Immunostaining]] showing IgA in the [[glomerulus]] of a patient with Henoch-Schönlein [[nephritis]].]]
The diagnosis is based on the combination of the symptoms, as very few other diseases cause the same symptoms together. [[Blood test]]s may show elevated [[creatinine]] and [[urea]] levels (in kidney involvement), raised [[IgA]] levels (in about 50%<ref name="Rai1999"/>), and raised [[C-reactive protein]] (CRP) or [[erythrocyte sedimentation rate]] (ESR) results; none are specific for Henoch-Schönlein purpura. The [[platelet]] count may be raised, and distinguishes it from diseases where low platelets are the cause of the purpura, such as [[idiopathic thrombocytopenic purpura]] and [[thrombotic thrombocytopenic purpura]].<ref name=Kraft1998/>
If there is doubt about the cause of the skin lesions, a [[biopsy]] of the skin may be performed to distinguish the purpura from other diseases that cause purpura, such as [[vasculitis]] due to [[cryoglobulinemia]]; on microscopy the appearances are of a [[hypersensitivity vasculitis]] and [[immunofluorescence]] demonstrates IgA and [[C3 (complement)|C3]] (a protein of the [[complement system]]) in the blood vessel wall.<ref name=Kraft1998/>
On the basis of symptoms, it is possible to distinguish HSP from [[hypersensitivity vasculitis]] (HV). In a series comparing 85 HSP patients with 93 HV patients, five symptoms were found to be indicative of HSP: palpable purpura, [[abdominal angina]], digestive tract hemorrhage (not due to intussussception), hematuria and age less than 20. The presence of three or more of these indicators has an 87% [[Sensitivity (tests)|sensitivity]] for predicting HSP.<ref name="pmid1613701">{{cite journal |author=Michel BA, Hunder GG, Bloch DA, Calabrese LH |title=Hypersensitivity vasculitis and Henoch-Schönlein purpura: a comparison between the 2 disorders |journal=J. Rheumatol. |volume=19 |issue=5 |pages=721–8 |year=1992 |pmid=1613701}}</ref>
Biopsy of the [[kidney]] may be performed both to establish the diagnosis or to assess the severity of already suspected kidney disease. The main findings on kidney biopsy are increased cells in the [[mesangium]] (part of the [[glomerulus]], where blood is filtered), [[white blood cell]]s, and the development of [[crescentic glomerulonephritis|crescents]]. The changes are indistinguishable from those observed [[IgA nephropathy]].<ref name="Rai1999">{{cite journal |author=Rai A, Nast C, Adler S |title=Henoch-Schönlein purpura nephritis |journal=J. Am. Soc. Nephrol. |volume=10 |issue=12 |pages=2637–44 |year=1999 |pmid=10589705 |url=http://jasn.asnjournals.org/cgi/content/full/10/12/2637}}</ref>
== Criteria ==
Multiple standards exist for defining Henoch-Schönlein purpura. These include the 1990 [[American College of Rheumatology]] (ACR) classification<ref name="pmid2202310">{{cite journal |author=Mills JA, Michel BA, Bloch DA, ''et al'' |title=The American College of Rheumatology 1990 criteria for the classification of Henoch-Schönlein purpura |journal=Arthritis Rheum. |volume=33 |issue=8 |pages=1114–21 |year=1990 |pmid=2202310 |doi=}}</ref><ref name="ACRcriteria">{{cite web |url=http://www.rheumatology.org/publications/classification/hsp.asp |title=1990 criteria for the classification of Henoch-Schönlein purpura |accessdate=2007-12-15 |format= |work=}}</ref> and the 1994 Chapel Hill Consensus Conference (CHCC).<ref name="pmid8129773">{{cite journal |author=Jennette JC, Falk RJ, Andrassy K, ''et al'' |title=Nomenclature of systemic vasculitides. Proposal of an international consensus conference |journal=Arthritis Rheum. |volume=37 |issue=2 |pages=187–92 |year=1994 |pmid=8129773 |doi=}}</ref> Some have reported the ACR criteria to be more [[Sensitivity (tests)|sensitive]] than those of the CHCC.<ref name="pmid12139664">{{cite journal |author=Murali NS, George R, John GT, ''et al'' |title=Problems of classification of Henoch Schonlein purpura: an Indian perspective |journal=Clin. Exp. Dermatol. |volume=27 |issue=4 |pages=260–3 |year=2002 |pmid=12139664 |doi=10.1046/j.1365-2230.2002.01063.x}}</ref>
== Pathophysiology ==
[[Image:HSP IF IgA.jpg|thumb|200px|right|Microphotograph of a [[histology|histological section]] of human skin prepared for direct [[immunofluorescence]] using an anti-IgA antibody. The skin is a biopsy of a patient with '''Henoch-Schonlein purpura'''. IgA deposits are found in the walls of small superficial capillaries (yellow arrows). The pale wavy green area on top is the [[Epidermis (skin)|epidermis]], the bottom fibrous area is the [[dermis]].]]
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]]'',<ref name=Saulsbury2001/> [[measles]], [[mumps]], [[rubella]], [[mycoplasma]] and numerous others.<ref name=Rai1999/> Drugs linked to HSP, usually as an idiosyncratic reaction, include the antibiotics [[vancomycin]] and [[cefuroxime]], [[ACE inhibitor]]s [[enalapril]] and [[captopril]], anti-inflammatory agent [[diclofenac]], as well as [[ranitidine]] and [[streptokinase]].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.<ref name=Rai1999/>
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.<ref name=Rai1999/> 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.<ref name=Rai1999/><ref name=Saulsbury2001/>
== Treatment ==
[[Analgesia|Pain killers]] may be needed for the abdominal pain and joint pains. It is uncertain as to whether HSP needs treatment beyond controlling the symptoms. Most patients do not receive therapy because of the high spontaneous recovery rate. [[Glucocorticoid|Steroids]] are generally avoided.<ref name=Saulsbury2001/> However, if they are given early in the disease episode, the duration of symptoms may be shortened, and abdominal pain can improve significantly. Moreover, the chance of severe kidney problems is reduced.<ref name="pmid17974746">{{cite journal |author=Weiss PF, Feinstein JA, Luan X, Burnham JM, Feudtner C |title=Effects of corticosteroid on Henoch-Schönlein purpura: a systematic review |journal=Pediatrics |volume=120 |issue=5 |pages=1079–87 |year=2007 |pmid=17974746 |doi=10.1542/peds.2007-0667}}</ref>
Evidence of worsening kidney damage would normally prompt a kidney biopsy. Treatment may be indicated on the basis of the appearance of the biopsy sample; various treatments may be used, ranging from oral steroids to a combination of intravenous [[methylprednisolone]] (a potent steroid), [[cyclophosphamide]] and [[dipyridamole]] followed by prednisone. Other regimens include steroids/[[azathioprine]], and steroids/cyclophosphamide (with or without [[heparin]] and [[warfarin]]). [[Intravenous immunoglobulin]] (IVIG) is occasionally used.<ref name=Rai1999/>
== Prognosis ==
=== Recovery and recurrence ===
Overall prognosis is good in most patients, with one study showing recovery occurring in 94% and 89% of children and adults, respectively (some having needed treatment).<ref name="pmid9153547">{{cite journal |author=Blanco R, Martínez-Taboada VM, Rodríguez-Valverde V, García-Fuentes M, González-Gay MA |title=Henoch-Schönlein purpura in adulthood and childhood: two different expressions of the same syndrome |journal=Arthritis Rheum. |volume=40 |issue=5 |pages=859–64 |year=1997 |pmid=9153547 |doi=10.1002/art.1780400513}}</ref>
In children under ten, the condition recurs in about a third of all cases and usually within the first four months after the initial attack.<ref name="Saulsbury1999"/> Recurrence is more common in older children and adults.<ref name=Saulsbury2001/>
=== Kidney involvement ===
In adults, kidney involvement progresses to [[end-stage renal disease]] (ESRD) more often. In a UK series of 37 patients, 10 (27%) developed advanced kidney disease. Proteinuria, hypertension at presentation, and pathology features (crescentic changes, interstitial fibrosis and tubular atrophy) predicted progression.<ref name=Shrestha2006/>
The findings on renal biopsy correlate with the severity of symptoms: those with asymptomatic hematuria may only have focal mesangial proliferation while those with proteinuria may have marked cellular proliferation or even crescent formation. The number of crescentic glomeruli is an important prognostic factor in determining whether the patient will develop chronic renal disease.<ref name=Saulsbury2001/>
In end-stage renal disease, some eventually need [[hemodialysis]] or equivalent renal replacement therapy (RRT). If a [[kidney transplant]] is found for a patient on RRT, there is a risk of about 35% over 5 years that the disease will recur in the graft (transplanted kidney), and 11% that the graft will fail completely (requiring resumption of the RRT and a further transplant).<ref name=Rai1999/>
== Epidemiology ==
HSP occurs more often in children than in adults, and usually follows an [[upper respiratory tract infection]]. [[Median|Half of affected patients]] are below the age of six, and 90% under ten. It occurs more often in boys than in girls (about twice as often).<ref name=Saulsbury2001/>
The [[incidence (epidemiology)|incidence]] of HSP in children is about 20 per 100,000 children per year; this makes it the most common vasculitis in childhood.<ref name=Gardner-Medwin2002>{{cite journal |author=Gardner-Medwin JM, Dolezalova P, Cummins C, Southwood TR |title=Incidence of Henoch-Schönlein purpura, Kawasaki disease, and rare vasculitides in children of different ethnic origins |journal=Lancet |volume=360 |issue=9341 |pages=1197–202 |year=2002 |pmid=12401245 |doi=}}</ref>
== History ==
The disease is eponymously named after [[Eduard Heinrich Henoch]] (1820-1910), a German [[pediatrics|pediatrician]], and his teacher [[Johann Lukas Schönlein]] (1793-1864), who described it in the 1860s. However the English [[internal medicine|physician]] [[William Heberden]] (1710-1801) and the [[dermatology|dermatologist]] Robert Willan (1757-1812) had already described the disease in 1802 and 1808, respectively, but the name ''Heberden-Willan disease'' has fallen into disuse. [[William Osler]] was the first to recognise the underlying [[allergy|allergic]] mechanism of HSP.<ref>{{WhoNamedIt|synd|1022|Schönlein-Henoch purpura}}</ref>
== References ==
{{reflist|2}}
{{Hematology}}
[[Category:Rheumatology]]
[[Category:Pediatrics]]
[[Category:Nephrology]]
[[Category:Autoimmune diseases]]
[[Category:Ailments of unknown etiology]]
[[de:Purpura Schönlein-Henoch]]
[[es:Púrpura de Schönlein-Henoch]]
[[fr:Purpura rhumatoïde]]
[[it:Porpora di Schonlein-Henoch]]
[[nl:Purpura van Henoch-Schönlein]]
[[ja:アレルギー性紫斑病]]
[[pl:Choroba Schönleina-Henocha]]
[[pt:Púrpura de Henoch-Schönlein]]
[[sv:Henoch-Schönleins purpura]]