Endgames Picture Quiz

Petechial rash on the extremities

BMJ 2009; 338 doi: http://dx.doi.org/10.1136/bmj.b1284 (Published 15 April 2009) Cite this as: BMJ 2009;338:b1284
  1. Stephanie St Pierre, medical student1,
  2. Marisa Potter, dermatology resident2,
  3. Scott P Prawer, dermatology resident (graduated), dermatologist23,
  4. Pitiporn Suwattee, assistant professor of dermatology4
  1. 1University of Minnesota Medical School, Minneapolis, MN, 55455 USA
  2. 2Department of Dermatology, University of Minnesota, Minneapolis, MN, 55455 USA
  3. 3Private Practice, Fridley, MN, 55432 USA
  4. 4Minneapolis Veterans Affairs Medical Center, Minneapolis, MN, 55417 USA
  1. Correspondence to: P Suwattee suwat001{at}umn.edu

    A 53 year old, afebrile woman presented to the dermatology clinic with a two week history of petechial rash on her lower extremities that had progressed up to her arms. In addition, she also had pain in the wrists, knees, and elbows. Approximately five months earlier, she had been diagnosed with group A streptococcal pharyngeal infection, but she had not been treated with antibiotics. She was currently taking salbutamol, famciclovir, levothyroxine, lovastatin, and varenicline. A systems review was unremarkable and she had no reported haematuria, abdominal pain, or bloody stools.

    A physical examination found multiple petechial macules, papules, and purpuric plaques, which were more numerous on the legs than on the arms (figure[F1]). A complete blood count and coagulation studies were normal. Urinalysis showed haematuria and proteinuria. A skin biopsy of a petechial papule revealed leucocytoclastic vasculitis, with a granular IgA reactivity around the blood vessels in the papillary dermis.

    Questions

    • 1 What additional investigative studies could be useful in a patient with palpable purpura?

    • 2 What is the most likely diagnosis in our patient?

    • 3 What are the adverse sequelae of this disease?

    Answers

    Short answers

    • 1 Additional studies should include a faecal occult blood test, serology for hepatitis B and C, serum protein electrophoresis, anti-streptolysin O titre, and measurement of antinuclear antibodies, antineutrophil cytoplasmic antibodies, rheumatoid factor, serum immunoglobulins, and cryoglobulins. Abdominal ultrasound and renal biopsy may also be indicated.

    • 2 The most likely diagnosis is Henoch-Schönlein purpura or anaphylactoid purpura, a leucocytoclastic vasculitis of small vessels.

    • 3 Complications of Henoch-Schönlein purpura include nephritis or nephrotic syndrome, acute and chronic renal failure, gastrointestinal bleeding, intussusception, bowel obstruction, and bowel perforation.

    Long answers

    1 Investigations

    Cutaneous palpable purpura may signify small vessel vasculitis, which has many possible causes (box 1).1 2 Histological findings of leucocytoclastic vasculitis include fibrin deposition in the vessel walls, red blood cell extravasation, and neutrophilic leucocytoclasis.

    Box 1 Causes of leucocytoclastic vasculitis12

    • Infections: β haemolytic streptococcal infection, Clostridium difficile, Helicobacter pylori, Mycobacterium tuberculosis, bacterial endocarditis, hepatitis B, hepatitis C, HIV, measles, mumps, varicella, parvovirus B19, coxsackie virus, adenovirus

    • Drugs: non-steroidal anti-inflammatory drugs, β lactam antibiotics, diuretics, vancomycin, ranitidine, cefuroxime, diclofenac, streptokinase, and angiotensin converting enzyme inhibitors

    • Collagen vascular diseases: rheumatoid arthritis, systemic lupus erythematosus, Sjögren syndrome, mixed cryoglobulinaemia (type II and type III)

    • Inflammatory bowel disease: ulcerative colitis, Crohn’s disease

    • Primary systemic vasculitides: Henoch-Schönlein purpura, antineutrophil cytoplasmic antibody associated vasculitis, urticarial vasculitis, polyarteritis nodosa

    • Other: acute haemorraghic oedema of infancy, hairy cell leukaemia, multiple myeloma, non-Hodgkin’s lymphoma, prostate cancer, non-small cell lung cancer, food additives, exposure to cold

    Patients who present with leucocytoclastic vasculitis should have a detailed history taken, and a thorough physical examination and laboratory work-up should be performed.2 A complete blood count, platelet count, peripheral blood smear, and coagulation studies help rule out haematological causes. Urinalysis, estimation of glomerular filtration rate, a liver function test, urine protein to creatinine ratio, analysis of urine sediment, and measurement of blood urea nitrogen, serum creatinine, and proteinuria should be undertaken to look for renal or hepatic involvement. Serum protein electrophoresis may also be helpful. A raised erythrocyte sedimentation rate and C reactive protein concentration indicate ongoing inflammation.

    Serum complement, rheumatoid factor, antinuclear antibody, anti-double stranded DNA, extractable nuclear antigen, and antineutrophil cytoplasmic antibodies should be measured to search for immunological causes of leucocytoclastic vasculitis. Immunoglobulins should be measured because hypergammaglobulinaemia can cause purpura.

    Serology for hepatitis B and C, serum cryoglobulins, and cryofibrinogens may also help pinpoint the cause of vasculitis. Chest radiography and blood and urine cultures can detect occult infection. A positive pharyngeal culture and raised anti-streptolysin O and anti-DNAse B titres may indicate streptococcal infection.

    Echocardiography should be performed to look for endocarditis, and stools should be examined for occult blood to look for gastrointestinal involvement, especially if Henoch-Schönlein purpura is suspected.

    2 Likely diagnosis

    According to the new classification of vasculitides from the European League against Rheumatism (EULAR) and the Paediatric Rheumatology European Society (PRES), Henoch-Schönlein purpura is a type of non-granulomatous, predominantly small vessel vasculitis.3 Classic clinical features include palpable purpura, arthritis or arthralgias, and abdominal pain. Although diagnosis is typically made on a clinical basis only, skin biopsy is recommended in patients with atypical presentations. Henoch-Schönlein purpura is a small vessel vasculitis characterised by leucocytoclastic vasculitis with deposition of IgA and C3. Palpable purpura are mandatory for the diagnosis of Henoch-Schönlein purpura, according to the EULAR/PRES consensus (box 2).3

    Box 2 Criteria for classification of Henoch-Schönlein purpura (2006)3

    Palpable purpura (mandatory criterion) in the presence of at least one of the following features:

    • Diffuse abdominal pain

    • Any biopsy showing predominant IgA deposition

    • Arthritis (acute, any joint) or arthralgia

    • Renal involvement (haematuria or proteinuria)

    In Henoch-Schönlein purpura, palpable purpura are typically located on the lower extremities, often extending to the extensor aspects of the arms and buttocks, and they are the presenting symptom in 75% of cases.4 The condition usually resolves without treatment but may recur and last up to four months, particularly in adults. Arthralgias and arthritis, although usually transient, may be the presenting symptom in only 15-25% of cases. They are caused by periarticular oedema and inflammation.4 5 6 Abdominal pain may occur as a result of petechial eruptions of the gastrointestinal tract that causes submucosal haemorrhage and oedema.7 Melaena, bright red blood in the stool, and haematemesis are possible manifestations of gastrointestinal involvement. A faecal occult blood test is an important diagnostic test which should be done in all patients with suspected Henoch-Schönlein purpura. Other rare systemic manifestations include subtle encephalopathy, seizures, cerebral haemorrhages, and diffuse alveolar haemorrhage.8 Swelling and tenderness of the scrotum and penis has been reported in boys, as a result of generalised oedema secondary to hypoalbuminaemia from renal and gastrointestinal involvement.8 Although the condition occurs mainly in children, it is also seen in adults. The table highlights the differences between paediatric and adult presentations.

    Differences between childhood and adult Henoch-Schönlein purpura9 10

    View this table:

    Although the exact cause of Henoch-Schönlein purpura is unknown, it is thought to be an autoimmune reaction triggered by infection, particularly with group A streptococci, Clostridium difficile, Helicobacter pylori, Mycobacterium tuberculosis, measles, mumps, varicella, parvovirus B19, coxsackie virus, and adenovirus.11 12 Certain drugs are also implicated in the onset of the disease, including vancomycin, ranitidine, cefuroxime, diclofenac, streptokinase, and angiotensin converting enzyme inhibitors. Other reported associations are leukaemia, multiple myeloma, non-Hodgkin’s lymphoma, prostate cancer, non-small cell lung cancer, food allergies, and exposure to cold.12 13

    The pathogenesis of Henoch-Schönlein purpura is not known, but deposits of an abnormal IgA1 isotype have been found in the skin, glomerular membrane, and gastrointestinal blood vessels. The abnormal glycosylation of the IgA1 isotype has been found to cause molecular instability, which increases the risk of proteolysis.14 Serum concentrations of tumour necrosis factor α, a proinflammatory cytokine, have been found to correlate with the degree of renal impairment in Henoch-Schönlein purpura.15 Polymorphism of the gene encoding interleukin 1β may also correlate with the severity of nephropathy. Polymorphisms of the angiotensinogen and angiotensin converting enzyme genes may play a role in the development and the severity of Henoch-Schönlein purpura and associated nephropathy, but the data are conflicting.14

    3 Complications

    Although Henoch-Schönlein purpura is generally a self limiting disease that lasts about a month, rare but serious gastrointestinal and renal complications may occur. As stated earlier, genetic polymorphisms may be the predisposing or protective factors in developing these complications.

    One potentially serious gastrointestinal complication of Henoch-Schönlein purpura is intussusception, which occurs more commonly in children (1-5% of children with Henoch-Schönlein purpura).16 An abdominal ultrasound may be indicated in children with abdominal pain. Other less common complications include bowel perforation (with or without intussusception), pancreatitis, and massive gastrointestinal haemorrhage.17

    Renal complications carry a high morbidity in patients with Henoch-Schönlein purpura. Although otherwise indistinguishable from IgA nephropathy, Henoch-Schönlein purpura associated nephritis may manifest with focal and segmental proliferative glomerulonephritis and crescent formation.14 IgA and C3 are deposited around the capillaries, venules, and in the glomeruli. In addition, IgG, IgM, and fibrin may be deposited in the renal mesangium. In one retrospective study with mean follow-up of just under five years, chronic renal insufficiency occurred in up to 15% of adults and 7% of children with kidney disease severe enough to warrant biopsy.18 In addition, proteinuria greater than 1 g in 24 hours may be associated with the development of end stage renal disease.19 Urine analysis will indicate the degree of haematuria and proteinuria, if any, and if these analyses are abnormal, kidney biopsy may be indicated.

    Treatment of Henoch-Schönlein purpura is mainly supportive care and removal of possible precipitating causes. Analgesics are indicated for joint and abdominal pain.20 Systemic steroids have been used in patients with arthralgia or arthritis, gastrointestinal haemorrhages, and kidney involvement. These drugs do not stop or alter the courses of the disease process, particularly in the case of associated acute renal disease with haematuria and proteinuria.21 Cyclophosphamide, azathioprine, plasmapheresis, and intravenous immunoglobulin have shown limited success.8

    Our patient had a kidney biopsy because of persistent haematuria and proteinuria. She was found to have IgA nephropathy with focal segmental necrosis and crescent formation.

    She was treated with prednisolone 60 mg daily and her skin lesions rapidly improved. However, she developed hypertension and hyperglycaemia, probably as a result of the drug treatment. Prednisolone was lowered to 40 mg daily and subcutaneous insulin was started. Her hypertension and blood glucose subsequently improved. At follow-up her haematuria and proteinuria had resolved, and systemic steroids were gradually reduced.

    Notes

    Cite this as: BMJ 2009;338:b1284

    Footnotes

    • Competing interests: None declared.

    • Provenance and peer review: Not commissioned; externally peer reviewed.

    • Patient consent obtained.

    References