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Systemic vasculitis and atypical infections: report of two cases
  1. Kuntal Chakravartya,
  2. Peter Merryb
  1. aDepartment of Rheumatology, Havering Hospital NHS Trust, UK, bDepartment of Rheumatology, Norfolk and Norwich Hospital, Norwich, Norfolk, UK
  1. Dr Kuntal Chakravarty, Haroldwood Hospital, Gubbins Lane, Romford, Essex RM7 0BE, UK

Abstract

Two cases of systemic vasculitis are described; one presenting with adult Henoch-Schonlein purpura secondary to a concomitantChlamydia infection and the other with leucocytoclastic vasculitis and mesangioproliferative glomerulonephritis secondary to a recent parvovirus B19 infection. Association of chlamydial infection has not previously been described with Henoch-Schonlein purpura and this infection should, perhaps, be added to the list of aetiologies of this disease. Parvovirus B19 causing significant urinary sediment abnormalities associated with mesangioproliferative glomerulonephritis and leucocytoclastic vasculitis has also not been described previously.

  • vasculitis
  • Henoch-Schonlein purpura
  • Chlamydia infection
  • leucocytoclastic vasculitis
  • mesangial proliferative glomerulonephritis
  • parvovirus B19

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Henoch-Schonlein purpura (HSP) is an inflammatory disease involving the skin, joints, gastrointestinal tract and kidneys.1 HSP is predominantly a disease of childhood and the clinicopathological features, as well as the long term outcome, have been studied extensively in children,2-4 although little information is available about the disease in adults. The exact aetiology of the disease is unknown, although the seasonal association suggests that there may be an infectious aetiology. Similarly, parvovirus B19 infection is predominantly a disease of childhood and its association in adults with severe systemic symptoms and concomitant skin and renal involvement has rarely been reported.

We describe two adult patients with systemic vasculitis with major organ involvement, both of whom were subsequently found to have occult systemic infection. These cases highlight the importance of looking for infection, including unusual viruses, in patients with systemic vasculitis.

Case reports

Case 1

A 28-year-old previously fit woman presented in April 1992 with general malaise, vague arthralgia and a maculopapular rash in her lower extremities. She admitted to a weight loss of 12.7 kg and recurrent abdominal pain but no diarrhoea. She had no chest symptoms apart from a recent onset of cough. She had no systemic signs of infection such as pyrexia or nocturnal sweats. She had no features of diseases such as systemic lupus erythematosus, iritis, psoriasis or colitis.

Physical examination revealed an apparently fit woman with an extensive purpuric rash on her lower extremities and abdomen. She was apyrexial and her heart rate was 64 beats/minute with a supine blood pressure of 110/60 mmHg. Examination of her chest revealed fine crepitations at bases. Systemic examinations, including joints, were normal.

Investigations showed a haemoglobin concentration of 13.8 g/dl, a white cell count of 9.5 × 109/l and an erythrocyte sedimentation rate of 40 mm in 1st hour. Liver and renal functions were normal as was the bone biochemistry. Microbiological investigations including blood and urine culture were negative. Immunological investigations for autoimmune and vasculitic diseases including antinuclear antibody (ANA), antineutrophil cytoplasm antibody (ANCA), antibody to double-stranded DNA, and antibody to cardiolipin, were all negative, as were viral antibodies to Epstein-Barr virus, hepatitis A, B and C, Coxsackie and parvovirus. Dip-stick test of urine showed the presence of 2+ red cells and 3+ protein. Mid-stream urinanalysis revealed presence of red cells (500/l); 24-hour protein excretion was 0.78 g. Serum creatinine and creatinine clearance were within normal limits as were C-reactive protein and creatinine phosphokinase levels. Chest X-ray showed a homogenous shadow in the left mid-zone (figure 1). Atypical pneumonia screen showed an elevated titre ofChlamydia pneumoniae antibody >1:64, which rose to >1:128 after 10 days. Microbiological examination of sputum confirmed the presence of Chlamydia pneumoniae antigen by ELISA, as did immunofluorescence. An electrocardiogram and echocardiogram were normal .

Figure 1

Chest X-ray of case 1 showing consolidation in the left mid zone

A skin biopsy from the lesion revealed infiltration of the small vessels in the dermis by leucocytes with nuclear dust and extravasation of erythrocytes confirming leucocytoclastic vasculitis. Renal biopsy showed mild mesangial proliferative glomerulonephritis with granular deposits of IgA in the mesangium. No complement deposition was noted.

Treatment with antibiotics resulted in improvement in her chest X-ray but not her rash or her haematuria and proteinuria. Because of these persistent signs and symptoms, she was treated with oral prednisolone, 40 mg daily, which resulted in prompt clinical response. She has remained well on a low dose of prednisolone with no further recurrence of the rash or urinary abnormalities.

Case 2

A 48-year-old, previously fit woman presented with an acute onset of polyarthralgia involving large joints, malaise, and a non-pruritic maculopapular skin rash for 3 days. She also described mild paraesthesia in her extremities. She admitted to no symptoms suggestive of autoimmune disease. She had no family history of any major illness. On physical examination she was apyrexial and had an extensive maculopapular eruption over her extensor aspects. Systemic examination was normal with a blood pressure of 130/80 mmHg. There was no clinical evidence of inflammatory arthritis.

Investigations that were normal or negative included: full blood count, erythrocyte sedimentation rate, C-reactive protein, ANA, antibody to double-stranded DNA, antibody to extractable nuclear antigen, complements, ANCA, urea and electrolytes, liver function test, blood culture, and viral serology for hepatitis A, B, and C. The serology for parvovirus B19 revealed raised IgM levels, indicating a recent infection. A dip-stick test of urine showed 2+ proteinuria and 24-hour urinary excretion of protein was 4.2 g. A microscopic examination of urine showed hyaline, granular and cellular casts with a few red cells and less than 10 white cells/mm3. She also had a positive rheumatoid factor of 1/40.

X-Rays of the chest, hands, and feet were normal, as was the abdominal ultrasound. Biopsies were taken of the skin lesion and the kidney to ascertain the nature of these lesions. The biopsy of the skin lesion (figure 2) showed leucocytoclastic vasculitis and the kidney biopsy (figure 3) showed mesangioproliferative glomerulonephritis. As her disease was clinically mild, no specific therapy was given and she made a spontaneous recovery. The urine abnormalities had completely resolved within 6 weeks. She has remained well for about 2 years with stable and normal renal function.

Figure 2

Skin biopsy of case 2 showing intense inflammatory cell infiltrate with abundance of nuclear dust around damaged dermal vessels; the epidermis appears normal

Figure 3

A single glomerulus is shown in this photograph from case 2. There is evidence of mild diffuse increase in the mesangial cellularity and matrix. The glomerular capillary loops are patent and the tubules appear normal

Discussion

The first patient presented with clinical features compatible with HSP. She had a typical skin rash, arthralgia, abdominal pain, haematuria, proteinuria and IgA deposition in her skin and kidneys. The only additional feature was the respiratory involvement which was found to be due to Chlamydia pneumoniae infection and which responded to antibiotics. It is possible that these were coexistent or that one triggered the other, but in someone of her age, a chlamydial chest infection is relatively unusual and the coexistence of the chest symptoms and HSP make an aetiological link very likely. The fact that her rash had recurred intermittently since the onset of illness suggests that the chlamydia antigen acted as a trigger but may not be the entire explanation for her vasculitis.

It is well known that HSP follows infections, particularly those due to streptococcus, varicella, hepatitis and yersinia. Symptoms suggesting infection are present in over half the patients in some series.5 Most commonly these consist of acute bronchitis, pharyngitis and flu-like symptoms, sometimes with a distinct interval between the infection and the onset of HSP. A seasonal variation has also been reported which is compatible with infection. The association with chlamydial infection has not been previously described, however.

Renal disease is a feature of HSP and many of the other vasculitides. Renal vasculitis is most often described following viral infections, particularly hepatitis B, but has not been reported previously in association with parvovirus B19 infection. Small vessel vasculitis (leucocytoclastic vasculitis) is the most common vasculitic manifestation associated with acute or chronic infections. The most frequently affected vessels are post-capillary vessels, capillaries and, less often, arterioles. It is generally believed that viral infections, particularly those caused by RNA viruses, seem to be associated with, or to cause, vasculitides confined to relatively small vessels. Bacterial infections, on the other hand, tend to involve a spectrum of blood vessels, from small blood vessels to large arteries, while fungal infections are associated with or cause vasculitis that manifests as erythema nodosum or that seems to be associated with large arteries or the aorta. It is noteworthy that several forms of vasculitis have been reported after respiratory infections.6

Treatment of systemic vasculitis usually requires systemic steroids, often in high dose. Our first patient responded to low-dose steroid but the second required no treatment. This again would suggest that infection played a significant role as our patients might have expected to have more prolonged and more severe disease if they had not been specifically associated with the infections.

We have, therefore, reported these two cases of infection-related systemic vasculitis; the first case, to our knowledge, has not been previously described in the literature and the second showed a rather unusual urinary sediment abnormality. We feel that chlamydial pneumoniae should be added to the long list of microbes causing vasculitis, as misdiagnosis can have serious consequences.

References

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