Department of Genito-Urinary Medicine,
1 Department of Rheumatology,
2 Department of Renal Medicine,
3 Department of Morbid Anatomy and
4 Department of Immunology, Royal Hospitals NHS Trust, London, UK
Correspondence to:
C. J. Skinner, Department of Genito-Urinary Medicine, The Royal London Hospital, Whitechapel, London E1 1BB, UK.
SIR, A 39-yr-old Zambian woman, living in the UK for 1 yr, was admitted to another hospital with chronic diarrhoea. A rectal biopsy demonstrated granuloma formation and therapy was initiated on a presumptive basis for tuberculosis and Crohn's disease with mesalazine, rifampicin and isoniazid. Eleven months later, she was found to be HIV positive by ELISA, and 6 weeks later was admitted to our hospital with a 1 month history of arthralgia involving the shoulders, wrists, hands, knees and feet, and an intermittent fever. There was no history of joint swelling, haematuria or oliguria.
On examination, she was apyrexial with a blood pressure of 100/70 mmHg and there was a malar rash with hyperpigmentation. She had no peripheral oedema or joint swelling, but diffuse muscle tenderness was demonstrated. A firm, smooth, non-tender liver was palpable 5 cm below the costal margin. Laboratory investigations showed the following: haemoglobin 8.1 g/dl, white cell count 3.76x109 /l, platelet count 64x109 /l, CD4 count 220 cells/mm3 (22%), creatinine 231 µmol/l, creatine kinase 130 mmol/l, blood glucose 5.1 mmol/l; urinalysis 3+ red blood cells, granular casts, no growth; 24 h urine total protein 103 mg/day, creatinine clearance 33 ml/min. ANA was positive at a titre of 1:2560 with a homogeneous pattern, antibodies to double-stranded (ds) DNA were confirmed by immunofluorescence with crithidia and ELISA was positive at 355 IU/ml (normal: <102 IU/ml). Serum complement levels were normal, but anticardiolipin IgG and IgM antibodies were positive at titres of 43 GPL U/ml and 17 MPL U/ml, respectively. Other investigations were normal or negative: extractable nuclear antigens Ro, La, Sm, RNP, Jo-1, rheumatoid factor, antiglomerular basement membrane antibody, hepatitis B surface antigen, antibodies to hepatitis C and syphilis serology. An ultrasound demonstrated normal sized non-obstructed kidneys of normal echogenicity.
Percutaneous renal biopsy showed variable glomerular changes. There was moderate mesangial proliferation, focal gross capillary loop thickening and segmental necroses in 25% of tufts. There were several areas of tubular atrophy with hyaline casts and interstitial fibrosis with a dense mixed cellular infiltrate (Fig. 1). Immunohistochemical staining showed a diffuse granular pattern for IgG and complement along glomerular capillary walls, with mesangial deposits of IgA and IgM. The picture was consistent with a diagnosis of lupus nephritis type III (WHO classification) on a background of mesangial proliferation with focal membranous change.
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HIV infection may present with a variety of features also commonly seen in SLE, including rash, arthralgia, lymphadenopathy, fevers, renal impairment and haematological disorders. Additionally, a variety of autoimmune phenomena have been described, including the presence of ANA to titres of 1:160 and anticardiolipin antibodies [1]. Antibodies to dsDNA have not been identified in patients with HIV infection [2], and their presence in our patient would therefore strongly support a diagnosis of SLE. HIV and SLE can both be characterized by false-positive antibody tests; however, the positive RNA PCR confirms the diagnosis of HIV. HIV-associated nephropathy is characterized by a focal and segmental sclerosing glomerulopathy with severe tubulointerstitial disease, focal microcystic dilatation of tubules and tubular degenerative changes [3] which can mimic changes seen in SLE. Other renal lesions which have been described include immune complex type glomerulonephritis, interstitial nephritis and haemolytic uraemic syndrome.
The development of SLE in the context of pre-existing HIV infection has been reported in at least two adult patients [4]; however, a diagnosis of drug-induced lupus nephritis in association with HIV infection has not previously been described. Drug-induced lupus has been noted in patients taking mesalazine treatment for inflammatory bowel disease [5, 6], and is a well-known complication of isoniazid therapy. Existing guidelines for the diagnosis of drug-related lupus suggest that the presence of antibodies to dsDNA, multisystem involvement or renal disease are extremely uncommon and support the diagnosis of idiopathic SLE. Additionally, resolution of symptoms should occur within days to weeks of stopping the drug. However, there are several reported cases of sulphasalazine-induced lupus in which antibodies to dsDNA were present, disappearing 321 months after drug withdrawal [7, 8]. A case of olsalazine-induced lupus syndrome was also associated with antibodies to dsDNA and biopsy-confirmed lupus nephritis WHO class II [9]. These findings may suggest that the presence of antibodies to dsDNA and renal involvement do not preclude a diagnosis of drug-induced lupus. Fourteen months after presentation, this patient had serology more typical of drug-induced lupus, with antibodies to ssDNA and the absence of antibodies to extractable nuclear antigens. Furthermore, histone antibodies retrospectively tested positive on serum samples stored from the time of initial presentation to our hospital, further supporting a diagnosis of drug-induced lupus.
Reported cases of patients with SLE and HIV show a decline in lupus disease activity with increasing immunosuppression, and conversely zidovudine treatment resulted in increased lupus activity with immune restoration [10]. The introduction of antiretroviral therapy in our patient led to a sustained reduction in viral load to below the level of detection and a modest increase in CD4 count. The absence of clinical lupus activity in this setting supports a diagnosis of drug-induced lupus which responded to withdrawal of the offending agent or agents.
References