Hospital Medicine

Henoch-Schönlein purpura (IgA Vasculitis)

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I. What every physician needs to know.

Background

Henoch Schönlein Purpura (HSP) is the most common small vessel vasculitis seen in children. Though it affects children predominately, 10-28% of patients with HSP are adults. The disease has also been called Schönlein-Henoch purpura, anaphylactoid purpura and purpura rheumatica.

The 2012 International Chapel Hill Consensus Conference on the Nomenclature of Vasculitides (CHCC2012) outlined the names and definitions of the most common forms of vasculitis in a nomenclature rather than a diagnostic or classification system. In that schema, Henoch- Schönlein Purpura was named IgA vasculitis based on “the compelling body of literature indicating that abnormal IgA deposits in vessel walls are the defining pathophysiologic feature.” In HSP, the vasculitis is caused by immunoglobulin A (IgA1) dominant immune deposits and complement (C3) deposition in the small vessels (capillaries, venules or arterioles).

Leukocytoclastic vasculitis is the characteristic histopathologic finding, a general term describing neutophilic-mediated blood vessel inflammation. The skin, gastrointestinal system and kidneys are the primary organs affected, presenting with a classic clinical presentation of arthritis, purpura (without thrombocytopenia), abdominal pain and renal failure.

The disease manifests specifically with palpable purpura, primarily in the legs and buttocks. Vessel wall inflammation resulting in necrosis and tissue ischemia explain the clinical presentation of gastrointestinal hemorrhage and glomerulonephritis. Though the presentation is impressive, the course is usually self-limited. This more benign course sets HSP apart from the heterogeneous and often progressive nature of other small and medium-vessel vasculitides.

The most widely known criteria for evaluating Henoch Schönlein Purpura, along with the other vasculidities, have been the 1990 American Rheumatology Criterion (ARC) and now the 2012 Chapel Hill Conference Consensus. The most recent 2010 EULAR/Printo Criterion will be discussed in terms of current diagnostic criterion. Each attempts to account for diseases which have some overlap in clinical and serologic findings. Though each has limitations as diagnostic tools, they are useful in classifying the protean vasculitic states and in aiding in the diagnosis of ambiguous cases.

The 1990 ARC for HSP was established by comparing 85 patients diagnosed with HSP with 722 controls who had other vasculitides. Four criteria were identified:

  • Age less than, or equal to, 20 years at disease onset

  • Palpable purpura

  • Acute abdominal pain

  • Biopsy showing granulocytes in small arteriole or venule walls

The presence of 2 or more of these criteria had a sensitivity of 87.1% and specificity of 87.7%.

These criteria have been criticized primarily for restricting the diagnosis, by definition, to children (patients less than 20 years old).

The Chapel Hill Consensus Conference (CHCC) classified the major vasculitides by vessel size and inform our current schema for distinguishing a group of diseases which share many common features. Large vessel vasculitis is defined as arteritis involving the major branches of the aorta and include Takayasu Arteritis and Giant Cell (temporal) (GCA) arteritis, the former more common in children and adolescents, and the latter in adults.

Medium-size vasculitides are diseases of tributaries of the major arteries, and the visualized small arteries, not including venules and capillaries. Examples of medium-vessel vasculitis are Polyarteritis Nodosa and Kawasaki disease, the latter more common in children.

The small vessel diseases described by the CHCC are ANCA-associated vasculitis (AAV), IgA vasculitis (Henoch-Schönlein) (IgAV), Granulomatosis with Polyangitis (GPA) (Wegener’s granulomatosis), Eosinophilic granulomatosis with polyangitis (EPGA) (Churg Strauss), Microscopic polyangiitis, Immune complex vasculitis, Anti-glomerular basement membrane (anti-GBM) disease, Cryoglobulinemic vasculitis and cutaneous leukocytoclastic angiitis.

Variable-vessel vasculitis includes Behcet’s disease and Cogan’s syndrome.

Pathophysiology

In the case of HSP, the vasculitis involves an immune response characterized by inflammation of small vessels, capillaries, venules, and arterioles, incited by IgA immune-complex deposition. Leukocytoclastic vasculitis is the general histologic term for a neutrophilic vasculitis, manifest by the presence of polymorphonuclear cells, nuclear dust/debris and fibrin deposition in the lumen or in the vessel wall.

Leukocytoclasis may be seen in a number of other disease processes but is pathognomonic for HSP, when IgA complexes are identified by tissue biopsy. Tissue ischemia may result in most of the vascultidies, though is less common in HSP.

Renal biopsy shows mesangial, deposition of IgA and C3 by immunofluorescence, similar to IgA nephropathy (Berger disease). Thus, IgA deposition in tissues is not unique to HSP, but is also seen in IgA nephropathy and in dermatitis herpetaformis. HSP is, however, a multiorgan, systemic process.

Elevated serum IgA is also seen in AIDS, but does not result in glomerulonephritis. IgA has 2 subclasses,IgA1 and IgA2, but IgA1 alone is implicated in the infiltrative deposition in HSP. This may be a result of abnormal glycosylation of O-linked oligosaccharides in the hinge region of IgA1.

Many inciting factors have been recognized, but the mechanism by which they trigger disease have not been fully characterized. Due to the presence of IgA and the presentation of disease following respiratory system, the mucosal immune system may play a role in the pathogenesis.

Infections and environmental triggers may be associated, but may be epiphenomena rather than a causal relationship. A significant number of children present following an upper respiratory infection. The disease has been reported to occur more commonly in late fall, early winter.

There have been case reports of HSP following vaccinations. There is no evidence linking meningiococcal vaccination with HSP in a large review. After the 2009 influenza A (H1N1) pandemic, four patients developed HSP shortly after vaccine administration. In all cases, patients recovered. The low incidence and unclear causal relationship does not restrict current recommendations for administration of yearly influenza vaccinations.

Genetic predisposition based on human leukocyte antigen alleles has been posited for Caucasian patients. HLA-DRB1*01 is statistically increased in HSP patient compared to controls (43% vs 7%) looking at a Spanish cohort of patients with the HLA-DRB*0103 phenotype in 14% of patients vs 2% of controls (OR 8.27, p< 0.001).

II. Diagnostic Confirmation: Are you sure your patient has Henoch-Schönlein purpura?

In 2005, the Pediatric Rheumatology European Society (PRES) vasculitis working group proposed classification criteria for common childhood vasculitidies, HSP among them. In 2008, the Ankara Consensus Conference validated the earlier European League Against Rheumatism (EULAR) endorsed criteria for pediatric vaculitidies, including HSP. This validation was accomplished with the support of the Pediatric Rheumatology International Trials Organization (PRINTO).

The revised criteria removed the inclusion population of age < 18, increasing the specificity for disease to 75%. Mandatory criteria for HSP included purpura, "(commonly palpable and in crops) or petichiae, with lower limb predominance, not related to thrombocytopenia." This finding had an 89% sensitivity and 86% specificity. When purpura manifests in an atypical distribution, IgA deposits by biopsy is required. The other four criteria follow:

  1. Abdominal Pain: Diffuse abdominal colicky pain with acute onset assessed by history and physical examination. This may include intussusception and gastrointestinal bleeding. (61% sensitivity, 64% specificity)

  2. Histopathology: This is typically leukocytoclastic vasculitis with predominant IgA deposit or proliferative glomerulonephritis with predominate IgA deposit. (93% sensitive, 89% specific)

  3. Arthritis or arthralgias: Acute onset of arthritis defined as joint swelling or joint pain with limitation on motion. Arthralgia is defined as acute onset of joint pain without joint swelling or limitation in motion. (sensitivity 78%, specificity 42%)

  4. Renal involvement: Proteinuria above 0.3g/24 h or above 30mmol/mg on spot urine albumin/creatinine ratio, on a morning sample. Hematuria as defined by above 5 red blood cells/high power field or red blood cell casts in the urinary sediment. (sensitivity 33%, specificity 70%)

Purpura or petichae of lower limb predominance with at least one of the above four findings conferred a 100% sensitivity and 87% specificity for confirming a diagnosis of HSP.

A. History Part I: Pattern Recognition:

Clinical Presentation

Forty six percent of patients had a history of antecedent (usually upper) respiratory tract infection. One hundred percent had palpable purpura; 84% had significant arthralgias or proteinuria. All had either proteinuria or hematuria, and 49% had macroscopic hematuria, 46% had microscopic hematuria and 54% had gastrointestinal involvement. Thirty two percent had renal impairment at onset and 59% were hypertensive.

Palpable purpura are identified in crops, or as peticheae, primarily localized to the lower extremities and buttocks.

HSP commonly causes gastrointestinal hemorrhage and diarrhea, and intusesseption. Orchitis, pancreatitis, sclerosing ureteritis and peritonitis are encountered less frequently.

Nonclassical systemic involvement in this British review was seen in 41% of cases. These patients experienced epistaxis, episcleritis, peroneal nerve palsy, and hemoptysis. IgA level was elevated in only 4/37 patients, and 54% had an elevated ESR. Pulmonary involvement is rare, with 2.4% of 124 patients in one study having either diffuse alveolar hemorrhage or interstitial pneumonia.

B. History Part 2: Prevalence:

Prevalence at large is documented at 10-20 people per 100,000, with the majority of patients being less than 10 years of age.

According to a Vaccine Safety Database study, there is an incidence in 16-20 year olds of 4.2 per 100,000 in the United States. Similar trends were seen in a Japanese child population was 3.5 per 100,000, in data collected over three decades. The annual incidence in some geographic areas is higher. In Scotland, 20.3 to 26.7 cases per 100,000 children were identified between 1995 and 2007, with rates of disease highest in the winter and lowest in the summer.

The occurrence in adults has been extrapolated as rare as 14.3 per million, but many recent reviews have reported much higher numbers. A 2002 review of 124 patients at a single-center had 45% of patients in their study over 18 years old (range of 8 months-81 years, median age 15). Given that criteria have typically been limited to patients younger than 20 years old, there is likely under diagnosis in the adult population.

There is a male: female predominance (1.2-2.0:1). Median age of onset is 6-7 years old, with most patients presenting between ages 2 and 10.

Ethnic variation has been identified in a large epidemiologic UK study of a childhood population of 1.1 million. Asian children had the highest incidence of 24 per 100,000 per year, followed by white children (17.8). Black children had the lowest incidence of HSP (6.2 per 100,000).

HLA-B35 has been observed in increasing frequency in patients manifesting renal manifestations, but not with gastrointestinal disease, in a retrospective study in Spain. The HLA-DRB1* 01 phenotype has been seen with increasing frequency in patients with HSP.

C. History Part 3: Competing diagnoses that can mimic Henoch-Schönlein purpura.

Immune-complex disease

IGA nephropathy, like HSP, may also follow an upper respiratory infection and is the most common primary glomerulonephritis worldwide. IgA nephropathy is a disease limited to kidneys and is not a vasculitis. In IgA nephropathy, serum IgA is elevated in up to 50% of patients. Disease recurrence following renal transplants indicates a role of circulating immune complexes.

Hypocomplementemic uticarial vasculitis syndromes

  • Cutaneous Leukocytoclastic angiitis (CLA - IgM/ IgG)

  • Leukocytoclastic vasculitis secondary to drugs or infection (Hypersensitivity, allergic vasculitis)

  • Cryoglobinemia

  • Lupus

  • Serum-Sickness

  • Infective endocarditis

  • Infantile haemorrhagic edema/Finkelstein purpura/ acute hemorrhagic edema

  • Dermatitis Herpetaformis

ANCA-associated vasculitis

  • Microscopic polyarteritis/polyangiitis, can also present with abdominal pain, renal failure and purpura, but has a more fulminant course and has a high risk of organ failure, as opposed to HSP.

  • Granulomatosis with Polyangiitis (GPA) (Wegener’s granulomatosis)

  • Eosinophilic granulomatosis with polyangiitis (EPGA) (Churg-Strauss)

Infectious vasculitis

  • Rocky Mountain Spotted Fever/Ricketsial disease

  • Bacterial Meningitis

Medium vessel vasculitis

  • Polyarteritis Nodosa

  • Kawasaki Disease

Connective tissue disease vasculitis (Lupus, Rheumatoid Arthritis, Sjogren’s syndrome)

  • Thrombotic thrombocytopenic purpura/Hemolytic Uremic syndrome

  • Scurvy

  • Disseminated Intravascular Coagulation

  • Infectious diarrhea (Campylobacter, Entamaebae histolytica, Shigella

  • Juvenile arthritis

  • Reactive arthritis

D. Physical Examination Findings.

The arthritis is typically migratory, oligoarthritis, transient, and typically in large joints. Patients may simply have arthralgias, without physical evidence of inflammation.

Palpable purpura are identified in crops, or as petichae, primarily distributed on the lower extremities and buttocks. Purpura is Latin for purple, and represents extravasation of blood outside of the blood vessel. It is, by definition, non-blanching.

Diascopy is the special technique clinicians can use to distinguish erythema and vascular engorgement from hemorrhage and purpura. Placing a glass slide over the lesion will cause the color to fade in the case of erythema, but not in the case of purpura.

Purpura can be further distinguished as palpable or nonpalpable. Non-palpable (macular) purpura occurs from blood vessel fragility or a bleeding disorder rather than from vessel inflammation. The presence of palpable purpura helps distinguish vasculitic-related purpura from non-vasculitic causes. Due to loss of elasticity in the skin with aging, the elderly may not present with palpable purpura, but rather, with ecchymosis.

Adults more commonly have been observed to have upper extremity purpura than children, while children have greater frequency of arthralgia.

Gastrointestinal bleeding is common. Adults are more prone to reports of diarrhea and are more likely to become anemic. 50% of patients have guaiac positive stools.

Pulmonary involvement is rare in children, but in adults can result in diffuse alveoloar hemorrhage or interstitial pneumonia.

E. What diagnostic tests should be performed?

Most clinicians follow the clinical ACR or EULAR criterion if the purpura are in a typical distribution and other criteria are met, obviating the need for a diagnostic biopsy. Biopsy supports diagnosis in ambiguous cases and facilitates prognosis in cases of significant renal impairment.

Skin biopsy shows perivascular IgA deposition in blood-vessel walls. Renal biopsy shows IgA deposition in the mesangium, sometimes crescentic formation. Light microscopy shows neutrophilic infiltration, specifically leukocytoclasis, which is neutrophil disintegration into nuclear dust, along with fibrin deposits and erythrocyte extravasation into the dermis. Direct immunofluorescence (DIF) is utilized in identifying the immunoglobulin and complement suspected of inducing purpuric vasculitis.

Intralesional biopsy rather than perilesional skin biopsy has been shown to have stronger intensity of immunoreactants. Of 65 patients in a prospective study evaluating DIF techniques in the evaluation of patients suspected of having vasculitis, the most commonly encountered immunoglobulin was IgA. Intralesional versus perilesional IgA deposition conferred a sensitivity of 82% and 68% respectively and a specificity of 73% and 66.7%.

Biopsy of purpuric lesions should be obtained from "the earliest, most symptomatic, reddish or purplish lesion" for the highest yield sample.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

As with the work-up of other vasculitic disease, the clinician must ascertain whether a more common diagnosis cannot explain the patient’s presentation.

Once vasculitis is suspected, distinguishing among the small vessel vasculitides would include evaluation for hepatitis and cryoglobulins, complement level, testing for anti-neutrophilic antibodies (ANCA). Biopsy will exclude small and medium vessel granulomatous vasculitis, including Wegener’s granulomatosis (GPA, granulomatous with polyangiitis) and Churg-Strauss syndrome.

Basic Initial work-up should include:

  • Complete blood count with differential. Platelet counts are normal. Mild leukocytosis may be present

  • PT, PTT

  • Peripheral blood smear

  • Stool Guaiac

  • Urinalysis

  • Urine protein: creatinine ratio or 24 hour urine protein collection

  • Biopsy: Skin or Kidneys

  • c-ANCA

  • p-ANCA

  • ANA

  • ASO, strep testing

  • C3, C4

  • IgA

  • SAA

  • HIV

  • Rheumatoid factor

  • Acute Hepatitis panel

Recent work on biomarkers in a group of 127 children diagnosed with HSP between 2012-2014 with age matched controls looked at 12 parameters –serum amyloid protein A (SAA), interleukin-6 (IL6), immunoglobulins (IgA, IgG, IgM and IgE), CRP, WBC count, complements C3 and C4, Anti-streptolysin O and ferritin. The HSP group had significantly higher levels of SAA, IL-6, CRP, EBC, IgA and IgM then the control group (p< 0.05) with SSA being the best with a sensitivity for disease of 95% and a specificity of 90%.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

  • Chest X-Ray: should be obtained as part of all vasculitic evaluations, to exclude infection and pulmonary hemorrhage.

  • Abdominal imaging, X-ray, ultrasound or computed tomography: should be obtained if intussusception is considered (see Figure 1).

Figure 1.

Lower extremity palpable purpura. Biopsy, leukocytoclastic vascultitis.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

Serum IgA is often checked, but lacks sensitivity and may be elevated in only approximately a third of cases. It can also be elevated in other disease processes.

III. Default Management

Clinical practice guidelines from the Kidney Disease Improving Global Outcomes (KDIGO) for HSP nephritis were published in 2012. The following recommendations were outlined:

1) Children with HSP nephritis and persistent proteinuria, > 0.5 g/d per 1.73m2, are treated with ACE-I or ARBs (2D).

2) Children with persistent proteinuria, >1g/dl per 1.73m2are treated after a trial of ACE-I or ARBs and GFR > 50 ml/min per 1.73m2, be treated the same as for IgAN with a 6-month course of corticosteroid therapy. Either of two regimens are outlined: IV bolus injections of 1 g methylprednisolone for 3 days each at months 1, 3 and 5 followed by oral steroid 0.5 mg/kg prednisone on alternate days for 6 months or Oral prednisone starting at 0.8-1 mg/kd/d for 2 months and then reduced by 0.2 mg/kg/d per month for the next 4 months (2D).

KDIGO blood pressure guidelines for IgA nephropathy are advised as < 130/80 mm Hg in patients with proteinuria < 1 g/d and < 125/75 mm HG when initial proteinuria is > 1 g/d (not graded) due to the prognostic factor proteinuria has in IgA nephropathy. Similar BP goals are not outlined for HSP nephritis.

3) Children with crescentic HSP with nephrotic syndrome and/or deteriorating kidney function are treated the same as for crescentic IgAN (2D).

The default management in the acute phase has been supportive, controlling abdominal pain and pain from arthralgias. There are few prospective, randomized control trials on corticosteroid use in HSP. Given the inflammatory nature of the disease, steroids would be expected to alter disease course, but they have shown discordant results during the past half century of use.

Most reports point toward use of steroids for treating severe abdominal pain and arthralgias, without altering the progression to end-stage renal disease. To that end, use of cytotoxic drugs has not been proven beneficial in a controlled trial, in altering the natural course or prognosis of the disease.

In contrast, in a Cochrane review of ten studies looking at intervention used to prevent and treat renal disease in HSP, no significant difference was seen in various conventional interventions. Prednisone therapy vs supportive treatment for 14 to 28 days at time points of 1 month to 1 year. The RR at 12 months between the prednisone groups and placebo was 1.02, 95% CI 0.4-2.62). The dosing and duration of treatment may be less and shorter that the present KDIGO guidelines recommend as a critique of this review.

In adults, steroid minimizing regimen was retrospectively studied after each group had 3 months of ACEI or ARB for moderate proteinuria. Mycophenolate Mofetil (1.0-1.5 g/d) plus lower dose prednisone (0.4-0.5 mg/kg/d) vs a corticosteroid (CS) group receiving full-dose prednisone of 0.8-1 mg/kg/d vs control showing remission rates in the MMF group, CS group and the control group of 72.7%, 71% and 48.4% at 6 months, suggesting studying MMF in prospective studies to help minimize high steroid dosed regimens.

A. Immediate management.

The immediate course of treatment is supportive. Excluding non-vasculitic disease processes such as infections, is imperative. Once the diagnosis has been made, treatment will focus on relieving pain, monitoring for gastrointestinal bleeding and intussusception, non-classic disease manifestations mentioned previously, and monitoring renal function.

Steroids have been shown to ameliorate abdominal pain and arthralgias.

Plasma Exchange has been employed with some success on the basis of case reports in patients with refractory disease with gastrointestinal involvement not responding to steroids or cyclophosphamide.

B. Physical Examination Tips to Guide Management.

  • Purpuric lesions typically last 3 to 10 days

  • Disease activity can be assessed, as for other vasculitides with the Birmingham Vasculits Activity Score

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

While hospitalized, renal function should be closely monitored on a daily basis. Depending on the degree of gastrointestinal bleeding at presentation, hemoglobin and hematocrit should be ordered to monitor resuscitation needs.

D. Long-term management.

A systematic review of 12 studies (1133 children) with HSP who did have nephritic/nephrotic syndrome or renal failure at presentation addressed the duration of follow-up. In the studies, follow-up ranged from 6 weeks to 36 years. Renal involvement in these children occurred in 34.2% of cases, either with proteinuria or hematuria.

One fifth of these ultimately developed nephrotic or nephritic syndrome, 85% within four weeks, and in 91% within six weeks, and in 97% within six months. ESRD did not develop in any patient with normal urinalysis, in 1.6% of those with isolated urinary abnormalities, and in almost 20% of those who had developed nephrotic or nephritic syndrome. Based on these outcomes, the authors recommend follow-up for six months in those whose urinalysis remains normal.

The majority of patients who develop Henoch-Schonlein nephritis (HSN) do so in the first one month from disease onset, typically by day 14 in one study. In this prospective study of 223 children under 16 years old, 46% developed HSN.

In their study, prednisone use did not affect progression of renal disease. Older children had higher incidence of nephritis. Weekly home dipstick measurements for proteinuria and hematuria have been advocated to monitor renal impairment as an outpatient setting during the first two months of treatment.

E. Common Pitfalls and Side-Effects of Management

Methylprednisolone and prednisone

Immunosuppression, avascular necrosis, hypertension, hyperglycemia, psychosis and osteoporosis attend chronic steroid use. Prolonged steroid use should prompt recommendations for daily calcium intake of 1200 mg/day and vitamin D intake of 800 international units/day.

ACEI/ARBS

Cough, hyperkalemia, acute kidney injury are among sequelae of treatment which need monitoring.

Cyclophosphamide

Cyclophosphamide is contraindicated in the first trimester of pregnancy and in breast feeding. Adverse effects include sterility and amenorrhea, making this a potentially unattractive initial treatment option for woman of child-bearing age. Other adverse effects include hemorrhagic cystitis, immunosuppression, bladder fibrosis, and pancytopenia. In patients with a Cr Cl below 10, the dose is decreased by 25%, while those on hemodialysis require 50% of the standard dosing.

Non-steroidal anti-inflammatory drugs

These may be used to ameliorate abdominal pain and arthralgias, but use will be limited in the setting of gastrointestinal bleeding and renal impairment.

IV. Management with Co-Morbidities

A. Renal Insufficiency.

Attention should be given to avoiding nephrotoxic agents and renal-dosing medications. NSAID use will be limited in the setting of renal impairment. Based on degree and severity of renal failure and proteinuria, ACEI or ARB may be indicated at discharge or at early follow-up appointments.

B. Liver Insufficiency.

Other than correcting coagulopathy, no special considerations are unique to this population. Supportive care can be accomplished with fresh frozen plasma, blood products for active bleeding and coagulopathy.

C. Systolic and Diastolic Heart Failure

No change in standard management.

D. Coronary Artery Disease or Peripheral Vascular Disease

Severe gastrointestinal bleeding leading to anemia can precipitate demand ischemia. Anemia has been shown to be a poor prognostic factor for patients with acute coronary syndrome. Transfusion thresholds for patients with acute coronary syndrome should be observed.

E. Diabetes or other Endocrine issues

Steroid use necessitates close glycemic monitoring in diabetic patients. There are no other special considerations in the hospital setting.

F. Malignancy

No change in management.

G. Immunosuppression (HIV, chronic steroids, etc.).

Steroid use portends increased risk of infection in the immunocompromised patient. Standard use of prophylactic antibiotics should be observed.

H. Primary Lung Disease (COPD, Asthma, ILD)

No change in management.

I. Gastrointestinal or Nutrition Issues

  • Steroids ameliorate abdominal pain and are often indicated in this population.

  • The National Kidney Foundation publishes online nutritional guidelines for patients with Chronic Kidney disease.

J. Hematologic or Coagulation Issues

Correcting coagulopathy and anemia will be part of supportive care in this population.

K. Dementia or Psychiatric Illness/Treatment

Steroid-induced psychosis, manifesting as hallucinations and delirium requires dose adjustment or discontinuation of steroids if symptoms are severe.

V. Transitions of Care

A. Sign-out considerations While Hospitalized.

Children with moderate to severe abdominal pain require serial abdominal exams. Sign-out should include a low threshold for abdominal imaging to exclude intussusception. Serial monitoring of hemoglobin in those with gastrointestinal bleeding, and regular evaluation of renal function with renal profile would be appropriate regular follow-up.

B. Anticipated Length of Stay.

Six clinical criteria which warrant admission include: orchitis, moderate or severe abdominal pain, arthritis involving more than two joints, proteinuria, clear evidence of gastrointestinal bleeding, and inability to ambulate as evidence-based admission criteria for pediatric HSP.

Many patients can be managed as an outpatient if the disease is mild. Children and the elderly may be vulnerable to dehydration and require inpatient resuscitation and supportive care. Severe renal failure or gastrointestinal manifestations will have longer hospital courses. One study evaluating pediatric patients with HSP reported 95% of patients stayed fewer than 10 days.

C. When is the Patient Ready for Discharge?

Generally, if renal function has stabilized and can be followed closely on an outpatient basis, and if pain and gastrointestinal bleeding has resolved, or is minimal, patients can be discharged. Patients who are volume resuscitated and can tolerate a diet meet discharge criteria.

D. Arranging for Clinic Follow-up

Clinic follow-up with the patient’s pediatrician or internist within a week of discharge can be arranged prior to discharge.

2. What tests should be conducted prior to discharge to enable best clinic first visit

Renal profile and urinalysis and CBC can be ordered prior to the first follow-up visit.

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

Chemistry and urinalysis with dipstick testing for protein and blood should be ordered.

E. Placement Considerations.

Because most patients are young, they have excellent recovery and transition from the hospital will generally be to the patient’s home. For those who have progressed to end-stage renal disease, venous access and placement for hemodialysis can be arranged in coordination with a social worker. Testing for hepatitis and temporary venous access should be done during hospitalization.

F. Prognosis and Patient Counseling.

Prognosis

The majority of patients have complete recovery and overall excellent prognosis. Advanced renal failure, nephrotic range proteinuria, crescent formation in above 50% of glomeruli portend the worst long-term prognosis.

In a study of children with idiopathic glomerulonephritis of multiple etiologies, resulting in nephrotic syndrome, steroid responsiveness was evaluated. Of the 210 patients, nearly 20% had immune-complex glomerulonephritis, but were not evaluated for steroid responsiveness due to not receiving four weeks of steroids. Of those studied, 71% had complete remission with four weeks of steroids. Fourteen percent had partial remission (PR) defined by resolution of edema with presence of proteinuria, and 15% were steroid resistant (SR).

Disappearance of proteinuria took 2.7 +/- 1.3 weeks for mean remission. Characteristics which correlated with steroid-resistance were older age, prevalence of hypertension and decreased GFR after four weeks of treatment. There was higher incidence of SR in African American compared to white patients, but this, and gender did not meet statistical significance.

In this study, steroid sensitivity decreased to 61%, and steroid resistance increased to 39% over the long course. Relapse occurred more quickly in patients who developed late SR (2.2 months versus 5.4 months, p = 0.00006). Also statistically significant as a negative prognostic factor for late SR was experiencing relapse while still on steroids ( p= 0.01).

Long-term renal impairment occurs in up to 35% of adults who had glomerulonephritis with a childhood presentation of HSP compared with only 7% of adults who had had mild or no renal symptoms at onset (RR of 4.7% in one long- term follow-up study). Women who had HSP nephritis as children later developed complications during pregnancy in their adult years. The authors recommend close blood pressure monitoring and monitoring for proteinuria and renal population later in life for these female patients during pregnancy.

Late onset HSP > age 60 portended worse outcomes, with increase tendency toward CKD and ESRD (18/28, 64.3% vs 7/62 or 11.3% [p= 0.00]) in patients < 60 years at onset of disease in a single retrospective review of 100 patients. Other factors associated with long-term ESRD in adults included baseline renal function impairment and baseline proteinuria > 1 or 1.5 g/ day and degree of renal biopsy interstitial fibrosis, sclerotic glomeruli and fibrinoid necrosis.

One study showed obesity in children to be a negative prognostic factor for renal injury compared to non-obese children with HSP.

Patient counseling

Patients and parents of patients should be counseled to recognize signs and symptoms of disease recurrence, including rash, fatigue, gastrointestinal symptoms, joint pain and changes in urinary output.

VI. Patient Safety and Quality Measures

A. Core Indicator Standards and Documentation.

NO JCAHO core measures are exclusive to HSP.

Based on revised 2006 CDC guidelines, routine voluntary screening for HIV should be accomplished for patients entering the health care setting, with an opt-out option, without requiring a separate consent form. These recommendations are directed at people between the ages of 13 and 64 unless undiagnosed HIV infection in the patient population has been documented to be <0.1%.

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

Prophylaxis for venous thromboembolism will be required in the hospitalized patient. Pharmacologic prophylaxis with heparin or low molecular weight heparins will be contraindicated in the setting of gastrointestinal bleeding. Non-pharmacologic prophylaxis will be required.

Follow-up with a nephrologist, depending on the degree of renal impairment, and with the patient’s primary care physician should be established during admission. Nephrotic range proteinuria and progression to chronic kidney disease should prompt institution of an angiotensin converting enzyme (ACE) inhibitor or ARB.

If applicable, smokers should be counseled and given resources on smoking cessation.

Influenza and pneumococcal vaccinations should be offered prior to discharge depending on patient age and comorbidities.

What’s the evidence?

Matteson, E. "Notes on the history of eponymic idiopathic vasculitis. The disease of Henoch and Schönlein, Wegener, Churg and Straus, Horton, Takayasu, Becet and Kawasaki". Arthritis Care and Research. vol. 13. 2001. pp. 237-245.

Blanco, R, Martinez-Taboada, VM, Rodriguez-Valverde, V. "Henoch Schönlein purpura in adulthood and childhood: two different expressions of the same syndrome". Arthris Rheum. vol. 40. 1997. pp. 859-64.

Mills, JA, Michel, BA, Bloch, DA. "The American College of Rheumatology". Arthritis Rheum.2,. vol. 33. 1990. pp. 1114-1121.

Jeannette, JC, Falk, RJ, Andrassy, K. "Nomenclature of systemic vasculitides. Proposal of an international consensus conference". Arthritis Rheum. vol. 37. 1994. pp. 187-192.

Falk, CJ. "Small-Vessel Vasculitis". New England Journal of Medicine. 1997. pp. 1512-1523.

Carlson, JA. "The histological assessment of cutaneous vasculitis". Histopathology. vol. 56. 2010. pp. 3-23.

Saulsbury, FT. "Henoch-Schönlein purpura in children. Report of 100 patients and review of the literature". Medicine. vol. 78. 1999. pp. 395-409.

Cioc, A, Sedmak, D, Nuovo, G. "Parvovirus B 19 associated adult Henoch Schönlein purpura". Journal of Cutaneous Pathology. vol. 29. 2002. pp. 602-607.

Goodman, MJ, Nordin, JD, Belongia, EA, Mullooly, JP, Baggs, J. "Henoch-Schonlein Purpura and Polysaccharide Meningococcal Vaccine". Pediatrics. vol. 126. 2010. pp. 325-329.

Watanabe, T. "Henoch Schönlein purpura following influenza vaccinations during the pandemic of influenza A (HIN1)". Pediatric Nephrol. vol. 26. 2011. pp. 795-798.

"Centers for disease control and prevention: Vaccine safety".

Ozen, S, Pistorio, A, Iusan, SM. "EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008. Final classification criteria". Ann Rheum Dis. vol. 69. 2010. pp. 790-806.

Shrestha, S, Sumingan, N. "Henoch Schönlein purpura with nephritis in adults: adverse prognositic indicators in a UK population". QJM. vol. 99. 2006. pp. 253-265.

Jithpratuck, W, Eishenawy, Y, Saleh, H. "The clinical implications of adult-onset Henoch-Schönlein Purpura". Clinical and Molecular Allergy. vol. 9. 2011.

Nadrous, HF, Yu, AC, Specks, U, Ryu, JH. "Pulmonary Involvement in Henoch-Schönlein Purpura". Mayo Clinic Proceedings. vol. 79. 2004. pp. 1151-1157.

Mu, Y, Sun, D. "Value of different biomarkers for diagnosis of Henoch-Schonlein purpura in children". Zhongguo Dang Dai Er Ke Za Zhi. vol. 17. 2015. pp. 918-21.

Lopez-Mejias, R, Genre, F, Perez, BS. "HLA-DRB1 association with Henoch-Schonlein purpura". Arthritis Rheumatol. 2014.

Kawasaki, Y, Suyama, K, Yugeta, E, Katayose, M. "The incidence and severity of Henoch Schonlein purpura nephritis over a 22-year period in Fukushima Prefecture, Japan". Int Urol Nephrol. vol. 42. 2010. pp. 1023-9.

Penny, K, Fleming, M, Kazmierczak, D, Thomas, A. "An epidemiologic study of Henoch Schönlein purpura". Paediatri Nurs. vol. 22. 2010. pp. 30-35.

Gardner-Medwin, JMM, Dolezalova, P, Cummins, C, Southwood, T. "Incidence of Henoch-Schönlein pupura, Kawasaki disease, and rare vasculitides in children of different ethinic origins". The Lancet. vol. 360. 2002. pp. 1197-1202.

Kawakami, T. "New Algorithm (Kawakami algorithm) to diagnose primary cutaneous vasculitis". Journal of Dermatology. vol. 37. 2010. pp. 113-124.

Barnadas, MA, Perez, E, Gich, I. "Diagnostic, prognostic and pathogenic value of the direct immunofluorescence test in cutaneous leukocytoclastic vasculitis". Int J Dermatol. vol. 43. 2004. pp. 19-26.

Trapani, S, Micheli, A, Grisolia, F, Resti, M. "Henoch Schonlein Purpurain Childhood: Epidemiological and Clinical Analysis of 150 Cases over a 5-year period and review of literature". Seminars in Arthritis and Rheumatism. vol. 35. 2005. pp. 143-153.

"KDIGO Clinical Practice Guidelines for Glomerulonephritis". vol. Volume 2. 2012. pp. 218-220.

Gedalia, A. "Henoch-Schönlein pupura". Curr Rheumatol Rep. vol. 6. 2004. pp. 195-202.

Ronkainen, J, Koskimes, O, Ala-Houhala, M, Antikainen, M. "Early prednisone therapy in Henoch-Schonlein Purpura: A randomized, double-blind, placebo controlled trial". J Pediat. vol. 149. 2006. pp. 241-247.

Huber, A, King, J, McLaine, P, Klassen, T, Pothos, M. "A randomized, placebo-controlled trial of prednisone in early Henoch Schonlein Purpura". BMC Medicine. 2004. pp. 7.

Weiss, PF, Klink, Andrew, J, Localio, R. "Corticosteroids may improve clinical outcomes during hospitalization for Henoch Schönlein Purpura". Pediatrics. vol. 126. 2010. pp. 674.

Tarshish, P, Bernstein, JE, Chester, M. "Henoch-Schönlein purpura nephritis: course of disease and efficacy of cyclophosphamide". Pediatric Nephrology. vol. 19. 2004. pp. 51-56.

Pillebout, E, Alberti, C, Guillevin, L. "The CESAR study group. Addition of cyclophosphamide to steroids provides no benefit compared with steroids alone in treating adult patients withsevere Henoch Schönlein Purpura". Kidney International. vol. 78. 2010. pp. 495-502.

Chartapisak, W, Opastirakul, S, Hodson, EM, Eillis, NS, Craig, JC. "Interventions for preventing and treating kidney disease in Henoch Schönlein Purpura (HSP) Cochrane Review". Evidence Based Child Health: A Cochrane Review Journal. vol. 5. 2010. pp. 637-700.

Hong, S, Ahn, SM, Lim, DH. "Late-onset IgA vasculitis in adult patients exhibits distinct clinical characteristics and outcomes". Clin Exp Rheumatol. vol. 34. 2016. pp. 77-93.

Han, F, Chen, LL, Ren, PP. "Mycopheolate mofetil plus prednisone for inducing remission of Henoch Schönlein purpura nephritis: a retrospective study". J Zheijian Univ Sci B. vol. 16. 2015. pp. 772-9.

Zhao, YL, Liu, ZJ, Bai, XM. "Obesity increases the risk of renal involvement in children with Henoch- Schönlein purpura". Eur J Pediat. vol. 174. 2015. pp. 1357-63.

Audemard-Verger, A, Pillebout, E, Guillevin, L. "IgA vasculitis (Henoch- Schönlein purpura) in adults: Diagnostic and therapeutic aspects". Autoimmune Rev. vol. 14. 2015. pp. 579-85.

Basaran, O, Cakar, N, Uncu, N. "Plasma Exchange therapy for severe gastrointestinal involvement of Henoch Schönlein purpura in children". Clin Exp Rheumatol. vol. 33. 2015. pp. 176-80.

Masarweh, K, Horovitz, Y, Avital, A, Spiegel, R. "Establishing hospital admission criteria of Henoch-Schonlein purpura". Rheumatol Int. 2014. pp. 1497-503.

Kang, Y, Park, JS, Ha, YJ. "Difference in clinical manifestations and outcomes between adult and child patients with Henoch Schönlein purpura". J Korean Med Sci. 2014. pp. 198-203.

Demirkaya, E, Ozen, S, Pistorio, A. "Performance of Birmingham Vasculitis Activity Score and disease extent index in childhood vasculitides". Clin Exp Rheumatol. vol. 70. 2012. pp. 162-8.

Augusto, JF, Sayegh, J, Delapierre, L. "Addition of Plasma exchange to glucocorticoids for the treatment of severe Henoch- Schönlein purpura in adults:a case series". Am J Kidney Dis. vol. 59. 2012. pp. 663-9.

Pyne, D, Mootoo, R, Bhanji, A. "Colchicine for the treatment of recurrent Henoch-Schonlein purpura in an adult". Rheumatology. vol. 40. 2001. pp. 1430-1431.

Luqmani, RA, Bacon, PA, Moots, RJ, Janssen, BA. "Birmingham Vasculitis Activity Score (BVAS) Dim system necrotizing vasculitis". QJM. vol. 87. 1994. pp. 671-678.

Narchi, H. "Risk of long term renal impairment and duration of follow up recommended for Henoch-Schonlein purpura with normal or minimal urinary findings: a systematic review". Arch Dis Child. vol. 90. 2005. pp. 916-920.

Jauhola, O, Ronkainen, J, Koskmies, O. "Renal manifestations of Henoch-Schonlein purpura in a 6-month prospective study of 223 children". Arch Dis Child. vol. 95. 2010. pp. 877-882.

"National Kidney Foundation: Nutrition and chronic kidney disease".

Ronkainen, J, Nuutinen, M, Koskimies, O. "The adult kidney 24 years after childhood Henoch-Schonlein purpura; a retrospective cohort study". The Lancet. 2002. pp. 666-670.

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