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Henoch-Schönlein Purpura
Shani I. Muhammad, MD
image BASICS
DESCRIPTION
  • Henoch-Schönlein purpura (HSP) is a nonthrombocytopenic, predominantly IgA-mediated, small vessel vasculitis that affects multiple organ systems and occurs in both children and adults.
  • HSP is often self-limited, with the greatest morbidity and mortality attributable to long-term renal damage.
  • Characterized by a tetrad of purpuric skin lesions, arthralgia, abdominal pain, and nephropathies
EPIDEMIOLOGY
Incidence
  • Annual incidence: 135/1 million children and 3.4 to 14.3/1 million adults
  • Mean age of patients affected is 6 years; 90% <10 years of age but has been reported in patients age 6 months to 75 years old
  • Gender: Male-to-female ratio is 1.2:1.
  • Race/ethnicity: most common in Caucasians and Asians, less common among African Americans
Prevalence
  • Annual prevalence: 10 to 22/100,000 persons
  • Year-round occurrence; more common in late fall to early spring
ETIOLOGY AND PATHOPHYSIOLOGY
  • Autoimmune disorder in which IgA production is increased in response to trigger(s), IgA1 immune complexes then activate the complement pathway, leading to production of inflammatory cytokines and chemokines.
  • Immune complex deposition results in small vessel inflammation; fibrosis; and necrosis within skin, intestinal mucosa, joints, and kidneys.
  • No single etiologic agent has been identified.
  • Known triggers include infection, drugs, vaccinations, and insect bites.
  • Infectious antigens include (but are not limited to) group A Streptococcus (may be present in up to 30% of HSP-associated nephritis), parvovirus B19, Bartonella henselae, Helicobacter pylori, Haemophilus parainfluenzae, coxsackievirus, adenovirus, hepatitis A and B viruses, Mycoplasma, Epstein-Barr virus, varicella, Campylobacter, methicillin-resistant Staphylococcus aureus.
  • Drugs: acetaminophen, quinolones, etanercept, codeine, clarithromycin
  • Vaccinations: MMR (measles, mumps, rubella), pneumococcal, meningococcal, influenza, hepatitis B
Genetics
Associated with &agr;1-antitrypsin deficiency, familial Mediterranean fever, HLA-DRB1*01, HLA-B35
COMMONLY ASSOCIATED CONDITIONS
  • Malignancy (rare): Greatest association is with solid tumors, including lymphoma, prostate cancer, and non-small cell lung cancer, but also associated with multiple myeloma.
  • Studies suggest a possible relationship with H. pylori infection (1)[A].
image DIAGNOSIS
Palpable purpura and at least one of the following:
  • Diffuse abdominal pain
  • Biopsy with predominant IgA deposition
  • Arthralgia or arthritis
  • Renal involvement (hematuria or proteinuria)
  • Direct immunofluorescence showing IgA deposition (2)[A]
PHYSICAL EXAM
  • Rash (96% of cases, 74% primary presenting symptom):
    • May start as urticaria, develops into nonblanching purpura, with or without petechiae and ecchymoses, may also be bullous
    • Distribution usually symmetric, most commonly involving the lower extremities but may involve the face and trunk
  • Abdominal tenderness (66% of cases, 12% primary presenting symptom):
    • Evidence of GI hemorrhage (28% of cases)
  • Joint tenderness (64% of cases, 15% primary presenting symptom):
    • Mainly affects knees or ankles; may have associated warmth and limited range of motion, less commonly effusion; erythema is absent.
    • Mostly nonmigratory, transient, and nondeforming
  • Orchitis (5%):
    • Presents as scrotal swelling and tenderness, may have associated torsion
  • Renal disease (<1% primary presenting symptom):
    • Hypertension may be present.
  • Rarely, patients present with CNS or pulmonary involvement, which may manifest as signs of cerebral hemorrhage or diffuse interstitial pneumonia, respectively.
DIFFERENTIAL DIAGNOSIS
  • Infection:
    • Meningococcemia
    • Rocky Mountain spotted fever
    • Bacterial endocarditis
    • Rheumatic fever
  • Immune-mediated:
    • Polyarteritis nodosa
    • Wegener granulomatosis
    • Systemic lupus erythematosus
    • Kawasaki disease
  • Other:
    • Inflammatory bowel disease
    • Idiopathic thrombocytopenic purpura
    • Juvenile rheumatoid arthritis
    • Leukemia
    • Acute surgical abdomen
    • Child abuse
DIAGNOSTIC TESTS & INTERPRETATION
  • No single lab test confirms the diagnosis of HSP.
  • Labs directed toward excluding other illnesses and assessing degree of renal involvement
Initial Tests (lab, imaging)
The following are generally accepted as initial labs for HSP:
  • CBC:
    • Leukocytosis and thrombocytosis may occur. Thrombocytopenia indicates an alternative cause of purpura.
    • Hemoglobin is variable, depending on whether GI hemorrhage occurs.
  • Basic serum chemistry panel (electrolytes, BUN, creatinine:
    • Electrolyte imbalances or elevated creatinine indicate renal dysfunction.
  • Urinalysis:
    • Gross or microscopic hematuria, proteinuria, and red cell casts indicate renal dysfunction.
  • PT and PTT:
    • Normal in HSP
  • Imaging is not part of the routine workup for HSP but may be performed to rule out alternative etiologies or for evaluation of suspected complications, particularly in cases of GI and renal involvement. Initial imaging modalities to consider include the following:
    • Abdominal radiographs, with or without barium enema: evaluate for free abdominal air suggestive of bowel perforation
    • Abdominal ultrasound: sensitive for the detection of intramural bleeding in HSP and may also show thickened bowel wall, reduced peristalsis, intussusception
  • Renal ultrasound: evaluates for hydronephrosis in cases of renal failure
Follow-Up Tests & Special Considerations
The following labs are also useful in diagnosing HSP:
  • Blood culture:
    • To rule out sepsis/bacteremia when diagnosis is unclear
  • Acute phase reactants:
    • Expect mild elevation.
  • IgA level:
    • Often elevated, although nonspecific, nonsensitive
  • Visfatin levels (3)
  • Degree of elevation correlates with disease severity and likelihood of renal involvement (3).
  • Complement levels:
    • Normal; sometimes decreased
  • Antinuclear antibody/antineutrophil cytoplasmic antibody:
    • Negative
  • Antistreptolysin-O titer:
    • Evaluates for preceding streptococcal infection
  • Stool guaiac if suspected GI hemorrhage
  • CT arteriography may be necessary to identify the location of bleeding in patients with GI hemorrhage.
Diagnostic Procedures/Other
  • Renal biopsy: Obtain if diagnosis is uncertain or if nephrotic range proteinuria shows mesangial IgA deposition, mesangial proliferation, or, in severe cases, crescentic glomerulonephritis.
  • Skin biopsy of purpura: IgA deposition in the dermis on immunofluorescence (2)[A]
  • P.461

  • Endoscopy may be considered in cases of GI hemorrhage given symptomatic overlap of HSP with inflammatory bowel disease.
  • Barium enema may be therapeutic in some instances of intussusception, although surgical correction is commonly needed.
image TREATMENT
GENERAL MEASURES
Rest and elevation of affected areas may limit purpura.
MEDICATION
  • In the absence of renal dysfunction or complication, HSP is usually self-limited and best managed with supportive care.
  • NSAIDs are effective for symptomatic treatment of joint pain. Caution is advised in cases of GI hemorrhage; avoid use in cases of renal involvement and consider acetaminophen as an alternative.
  • Steroids given early in disease course using oral prednisone 1 to 2 mg/kg/day for 1 to 2 weeks decrease both duration of abdominal pain and severity of joint pain and may have benefit in preventing GI bleeding and causes of surgical abdomen, including intussusception.
  • Steroids have benefit in treatment of severe and/or bullous purpura.
  • Steroids given early in disease are effective for the acute treatment of crescentic nephritis and may prevent chronic renal disease in such patients.
  • Early intervention with steroids has no effect on the prevention or development of renal involvement after 1 year.
  • High-dose IV pulse steroids (500 mg to 1 g) may be considered in cases of mesenteric vasculitis and severe renal impairment. Evidence is very limited to support use of cyclophosphamide, plasmapheresis, and intravenous immunoglobulin (IVIG) for severe renal and GI involvement, as well as colchicine for severe skin lesions.
  • Mycophenolate mofetil (MMF) could be valuable in the treatment of complicated HSP (3,4)[A].
ISSUES FOR REFERRAL
  • Consider nephrology referral for renal biopsy if nephrotic range proteinuria at any time or proteinuria >100 mg/mmol for 3 months after diagnosis.
  • Dermatology referral for skin biopsy
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
  • Insufficient oral intake
  • Renal insufficiency
  • Severe abdominal pain
  • Severe GI bleeding
  • Altered mental status
  • Mobility restriction due to arthritis
  • HTN
  • Nephrotic syndrome
IV Fluids
Hydration should be maintained.
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
  • Patients should be seen weekly during the acute illness. Visits should include history and physical exam to include BP measurement and urinalysis.
  • Because ˜100% of patients who develop renal involvement will do so within 6 months of HSP diagnosis, all patients should be followed at least monthly with BP and urinalysis for a duration of no <6 months.
  • Women with a history of HSP should be monitored for proteinuria and HTN during pregnancy.
  • Consider workup for occult malignancy in patients with adult-onset HSP.
PATIENT EDUCATION
  • American Family Physician handout on HSP available at: http://www.aafp.org/afp/1998/0801/p411.html
  • National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC): http://www.niddk.nih.gov/health-information/health-topics/kidneydisease/henoch-sch%C3%B6nlein-purpura-hsp/Pages/facts.aspx
PROGNOSIS
  • Long-term prognosis heavily dependent on presence and severity of nephritis
  • HSP is self-limited in 94% of children and 89% of adults.
  • Most cases of HSP resolve within 4 weeks of diagnosis. Recurrence rate within 6 months of diagnosis is 33%.
  • Factors associated with poorer prognosis include age >8 years, fever at presentation, purpura above the waist, elevated ESR or IgA concentration, and increasing severity of renal histology grade.
  • Chronic renal disease occurs in up to 20% of children with nephritic and nephrotic syndrome compared with 50% of adults who had any renal involvement. Risk of long-term renal failure is ≤5%.
  • Risk factors that may result in renal failure include old age, HTN, elevated serum creatinine, and nephrotic and mixed nephritic-nephrotic syndrome at the onset of disease (3)[A].
REFERENCES
1. Kutlubay Z, Zara T, Engin B, et al. Helicobacter pylori infection and skin disorders. Hong Kong Med J. 2014;20(4):317-324.
2. Mysorekar VV, Sumathy TK, Shyam Prasad AL. Role of direct immunofluorescence in dermatological disorders. Indian Dermatol Online J. 2015;6(3): 172-180.
3. Nikibakhsh AA, Mahmoodzadeh H, Karamyyar M, et al. Treatment of severe henoch-schonlein purpura nephritis with mycophenolate mofetil. Saudi J Kidney Dis Transpl. 2014;25(4):858-863.
4. Antoon JW, Keane MW. Migratory polyarthritis in a child. Clin Pediatr (Phila). 2012;51(4):401-403.
Additional Reading
&NA;
  • Batu ED, Ozen S. Pediatric vasculitis. Curr Rheumatol Rep. 2012;14(2):121-129.
  • Boulis E, Majithia V, McMurray R. Adult-onset Henoch-Schonlein purpura with positive c-ANCA (anti-proteinase 3): case report and review of literature. Rheumatol Int. 2013;33(2):493-496.
  • Cao N, Chen T, Guo ZP, et al. Elevated serum levels of visfatin in patients with henoch-schönlein purpura. Ann Dermatol. 2014;26(3):303-307.
  • Dillon MJ, Ozen S. A new international classification of childhood vasculitis. Pediatr Nephrol. 2006;21(9): 1219-1222.
  • González LM, Janniger CK, Schwartz RA. Pediatric Henoch-Schönlein purpura. Int J Dermatol. 2009; 48(11):1157-1165.
  • Hoyer PF. Prevention of renal disease in Henoch-Schonlein purpura: clear evidence against steroids. Arch Dis Child. 2013;98(10):750-751.
  • Jithpratuck W, Elshenawy Y, Saleh H, et al. The clinical implications of adult-onset Henoch-Schonelin purpura. Clin Mol Allergy. 2011;9(1):9.
  • Kawasaki Y. The pathogenesis and treatment of pediatric Henoch-Schonlein purpura nephritis. Clin Exp Nephrol. 2011;15(5):648-657.
  • McCarthy HJ, Tizard EJ. Clinical practice: diagnosis and management of Henoch-Schönlein purpura. Eur J Pediatr. 2010;169(6):643-650.
  • Ozen S, Pistorio A, Iusan SM, et al. EULAR/PRINTO/PRES criteria for Henoch-Schönlein purpura, childhood polyarteritis nodosa, childhood Wegener granulomatosis and childhood Takayasu arteritis: Ankara 2008, part II: final classification criteria. Ann Rheum Dis. 2010;69(5):798-806.
  • Reamy BV, Williams PM, Lindsay TJ. Henoch-Schönlein purpura. Am Fam Physician. 2009;80(7):697-704.
  • Sohagia AB, Gunturu SG, Tong TR, et al. Henoch-Schonlein purpura—a case report and review of the literature. Gastroenterol Res Pract. 2010;2010:597648.
  • Trnka P. Henoch-Schönlein purpura in children. J Paediatr Child Health. 2013;49(12):995-1003.
  • Weiss PF, Klink AJ, Localio R, et al. Corticosteroids may improve clinical outcomes during hospitalization for Henoch-Schönlein purpura. Pediatrics. 2010;126:674-681.
Codes
&NA;
ICD10
D69.0 Allergic purpura
Clinical Pearls
&NA;
  • HSP is a systemic small vessel vasculitis characterized by clinical tetrad of palpable purpura, abdominal pain, arthralgia, and renal dysfunction.
  • The main form of treatment is supportive care, but oral corticosteroids are beneficial in certain circumstances.
  • In all patients with HSP, regardless of renal involvement at presentation, it is reasonable to check BP and urinalysis at weekly to monthly intervals for no <6 months after diagnosis to monitor for developing renal dysfunction.