Henoch–Schönlein purpura

IgA vasculitis, previously known as Henoch–Schönlein purpura (HSP), is an autoimmune disease that most commonly affects children. In the skin, the disease causes palpable purpura (small, raised areas of bleeding underneath the skin), often with joint pain (arthralgia) and abdominal pain. With kidney involvement, there may be a loss of small amounts of blood and protein in the urine (hematuria and proteinuria), but this usually goes unnoticed; in a small proportion of cases, the kidney involvement proceeds to chronic kidney disease (CKD). HSP is often preceded by an infection, such as a throat infection.

HSP is a systemic vasculitis (inflammation of blood vessels) and is characterized by deposition of immune complexes containing the antibody immunoglobulin A (IgA); the exact cause for this phenomenon is unknown. In children, it usually resolves within several weeks and requires no treatment apart from symptom control but may relapse in 1 out of 3 cases and cause irreversible kidney damage in about 1 in 100 cases. In adults, the prognosis is different from in children. The average duration of cutaneous lesions is 27.9 months. For many, it tends to be relapsing–remitting over a long period of time, rather than self-limiting and there tend to be more complications.

Signs and symptoms

thumb|Typical [[purpura on lower leg]]

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. Purpura occur in all cases, joint pains and arthritis in 80%, and abdominal pain in 62%. Some include gastrointestinal hemorrhage as a fourth criterion; this occurs in 33% of cases, sometimes, but not necessarily always, due to intussusception. 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. The joints involved tend to be the ankles, knees, and elbows, but arthritis in the hands and feet is possible; the arthritis is nonerosive and hence causes no permanent deformity.

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.

Pathophysiology

Henoch–Schönlein purpura is a small-vessel vasculitis in which complexes of immunoglobulin A (IgA) and complement component 3 (C3) are deposited on arterioles, capillaries, and venules (hence it is a type III hypersensitivity reaction). The activation of the alternative complement pathway results in the deposition of IgA aggregates or IgA complexes in target organs (with deposition of C3). This leads to the production of inflammatory mediators, including vascular prostaglandins like prostacyclin, which may play a key role in the development of IgAV and its organ-specific clinical manifestations. As with IgA nephropathy, serum levels of IgA are high in HSP and there are identical findings on renal biopsy; however, IgA nephropathy has a predilection for young adults while HSP is more predominant among children. Further, IgA nephropathy typically only affects the kidneys while HSP is a systemic disease. HSP involves the skin and connective tissues, scrotum, joints, gastrointestinal tract and kidneys.

It is hypothesized to involve autoimmunity triggered by infections. Streptococcus strains and Parainfluenza virus are the most commonly associated pathogens, and in children Human Parvovirus B19 is a frequent viral trigger

Diagnosis

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 tests may show elevated creatinine and urea levels (in kidney involvement), raised IgA levels (in about 50%

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 and Ig deposition in the mesangium (part of the glomerulus, where blood is filtered), white blood cells, and the development of crescents. The changes are indistinguishable from those observed in IgA nephropathy.

thumb|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–Schönlein purpura. IgA deposits are found in the walls of small superficial capillaries (yellow arrows). The pale wavy green area on top is the epidermis, the bottom fibrous area is the dermis.]]

HSP can develop after infections with streptococci (β-haemolytic, Lancefield group A), hepatitis B, herpes simplex virus, parvovirus B19, Coxsackievirus, adenovirus, Helicobacter pylori, and the 1994 Chapel Hill Consensus Conference (CHCC). Some have reported the ACR criteria to be more sensitive than those of the CHCC.

More recent classifications, the 2006 European League Against Rheumatism (EULAR) and Pediatric Rheumatology Society (PReS) classification, include palpable purpura as a mandatory criterion, together with at least one of the following findings: diffuse abdominal pain, predominant IgA deposition (confirmed on skin biopsy), acute arthritis in any joint, and renal involvement (as evidenced by the presence of blood and/or protein in the urine).

Differential diagnosis

Henoch–Schönlein purpura may present with an atypical manifestation, which can be confused with papular urticaria, systemic lupus erythematosus, meningococcemia, dermatitis herpetiformis, and acute hemorrhagic edema of infancy.

Treatment

As of 2017, the optimal way to treat Henoch–Schönlein purpura remains controversial. Analgesics may be needed for the abdominal and joint pains. Wound care is warranted if skin death and ulcerations occur. A systematic review did not find any evidence that steroid treatment (prednisone) is effective at decreasing the likelihood of developing long-term kidney disease.

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 steroids by mouth to a combination of intravenous methylprednisolone (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. There is also no evidence that treating children or adults with cyclophosphamide prevents severe kidney disease. Heparin treatment is not justified for people with HSP. In children under ten, the condition recurs in about a third of all cases, usually within the four months of the initial attack.

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.

Cases of HSP may occur anytime throughout the year, but some studies have found that fewer cases occur during the summer months.

History

alt=Johann Lukas Schönlein|thumb|Johann Lukas Schönlein

The disease is named after Eduard Heinrich Henoch (1820–1910), a German pediatrician (nephew of Moritz Heinrich Romberg, the pioneer of neurology) and his teacher Johann Lukas Schönlein (1793–1864). Johann Schönlein described the condition as an entity in 1837; Eduard Heinrich Henoch in 1868 reported the first case of a patient with colic, bloody diarrhea, painful joints, and a rash. The English physician William Heberden (1710–1801) and the 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. Moreover, Willan was the first to describe an exanthematous rash of childhood known as erythema infectiosum in 1799. In 1920, Eduard Glanzmann(1887-1959), a Swiss pediatrician noted for his contributions in the fields of infectious disease, vitamin therapy and, mostly the field of haematology. He recognised the role of allergy in the pathogenesis of Henoch–Schonlein purpura, hence the understanding of the allergic component in HSP. William Osler is also the first to recognise the underlying allergic mechanism of HSP. In 2012, the International Chapel Hill Consensus Conference Nomenclature of Vasculitides renamed HSP IgA vasculitis. Prior to this, the disease was more often known as Henoch–Schönlein purpura rather than the reverse.

In popular culture

The disease was featured in the TV series House in the season 6 episode "Open and Shut".