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Necrotising vasculitis is one of the pathological findings of mononeuropathy multiplex in patients infected with HIV. It is an infrequent complication that can occur at different stages of immunosuppression and with a prognosis correlating with the degree of immunocompetence.1-4 We report a patient with AIDS affected by necrotising vasculitis, who was successfully treated and followed up for 19 months.
A 35 year old woman with AIDS presented in February 1995 with a two week history of progressive weakness and pain of her right hand and a left foot drop. The patient had been followed up neurologically since March 1994 for a distal sensory neuropathy, confirmed by electrophysiological studies. Her distal sensory neuropathy involved the lower limbs and was thought to be a result of HIV infection but exacerbated by zalcitabine and didanosine.
Her medical history included recurrent pneumonia, syphilis, gonorrhoea, oral candidiasis, and Clostridium difficile colitis. Severe headaches had been evaluated in May 1994 with a normal MRI and lumbar puncture (venereal disease research laboratory test negative). Her CD4 count had dropped significantly from 392 to 94/mm3between February and December 1994.
In February 1995, her neurological examination showed normal cognition, language, and intact cranial nerves. Motor examination disclosed normal tone, intrinsic muscle weakness of the right hand involving muscles supplied by both median and ulnar nerve, and trace movement with attempted dorsiflexion of the left foot. Muscle stretch reflexes were symmetrically brisk but ankle jerks were absent. Plantar responses were flexor bilaterally. Skin evaluation indicated the presence of livedo reticularis. Electrophysiological studies showed a generalised axonal sensorimotor polyneuropathy with a superimposed mononeuropathy of the right median nerve.
Her packed cell volume was 29%, white cell count 2400/mm3, normal platelet count, CD4 cell count 103/mm3, sedimentation rate 15, positive antinuclear antibody 1:320 in a speckled pattern, cANCA 1:640 with negative antiproteinase-3, pANCA, rheumatoid factor, antidouble stranded DNA, cryoglobulins, and hepatitis B screening. Electrolytes and urinalysis were within normal limits. Cerebrospinal fluid showed 11 nucleated cells/ml (89% lymphocytes), glucose 50 mg/dl, protein 36 mg/dl. Chest radiography, CT of the sinuses, and renal function tests were all normal. Cytomegalovirus antibodies were present in the serum, but a polymerase chain reaction in blood was negative.
A combined biopsy of the left superficial peroneal nerve and peroneus brevis muscle was performed. The peroneus muscle showed evidence of moderate acute and chronic degeneration. Intramural as well as perivascular mononuclear cell infiltrates and fibrinoid necrosis with thrombosis of the perimysial blood vessels were noted. The superficial peroneal nerve showed severe reduction in the number of large myelinated fibres with evidence of frank fibre degeneration on teased nerve preparation. Several epineural blood vessels were thrombosed and recanalised. No cytomegalovirus inclusions were noted and cytomegalovirus immunostaining was negative.
After her biopsy results, 1g prednisolone was given intravenously for three days, followed by oral prednisone at 60 mg/day. The pain improved significantly after the second day of intravenous steroids without any change in her strength. Two months after initial treatment, her strength was improved; however, she had developed a cushingoid appearance and hypertension. Prednisone was slowly tapered to 20 mg/day but more symptoms developed in the right hand. In June 1995, the patient presented with pneumococcal pneumonia and pneumococcaemia. High dose steroids were restarted and 2 g/kg intravenous immunoglobulin (IVIg) monthly, was added. The patient’s strength improved further, and IVIg infusions were stopped after four consecutive months, while steroids were tapered slowly.
In October 1995, she was diagnosed with cytomegalovirus retinitis in the left eye and was treated with intravenous ganciclovir. Despite this intercurrent illness, the patient’s strength continued to improve, and she regained full abduction of her right fingers and left foot dorsiflexion. In May 1996, a protease inhibitor was added to her double nucleoside analogue antiretroviral regimen, and as of September 1996, the patient continues to be neurologically stable, off steroids for the past seven months.
Our patient’s nerve and muscle biopsy showed evidence of vasculitis with histological features similar to polyarteritis nodosa, as previously described in HIV infection.1-4 The mechanism(s) responsible for necrotising vasculitis is not well understood. It is possible that the presence of HIV antigens may trigger an immune reaction with activation of complement.1On the other hand HIV may play a more direct part given that HIV replication has been found in the proximity of the vasa nervorum.5
Cytomegalovirus infection is a common opportunistic condition in HIV infected patients with low CD4 cell count, and it has been associated with mononeuropathy multiplex.6 We concluded that cytomegalovirus was not responsible for mononeuropathy multiplex in this patient because at the time of presentation, there were no systemic manifestations of cytomegalovirus infection and the nerve and muscle biopsies were negative for either cytomegalovirus inclusions or specific cytomegalovirus immunostaining. In addition, we were unable to isolate cytomegalovirus from blood by using a polymerase chain reaction.
The therapeutic approach to necrotising vasculitis in patients with AIDS is problematic. The few available reports suggest that patients with high CD4 cell count (>200 per mm3) have a good prognosis and respond well to steroids.1 4 Patients with more severe immunosuppression have, in general, a poorer prognosis.2 3 The prolonged use of steroids alone, or in combination with a cytotoxic drug such as cyclophosphamide, can increase the risk of opportunistic infections in severely immunocompromised patients. Furthermore, the combination of steroids and cyclophosphamide has not been reported to be beneficial in patients with AIDS and necrotising vasculitis.2 3 On the other hand, IVIg has been reported to be useful in HIV seropositive patients with other inflammatory conditions such as polymyositis7and in a few HIV seronegative patients with systemic vasculitis,8 even permitting tapering of the standard treatment—that is, prednisone and cyclophosphamide. IVIg may be also valuable in severely immunosuppressed HIV infected patients for decreasing the risk of bacterial infections,9 therefore allowing a safer administration of immunosuppressive treatment.
The patient we describe improved and has remained stable 19 months since the onset of necrotising vasculitis, after treatment with a combination of steroids and IVIg. We can only speculate on the contribution of IVIg in the successful treatment of this one patient. We suggest that steroids remain the drug of choice in patients with AIDS and necrotising vasculitis. Nevertheless, IVIg may be a useful adjunctive therapy allowing the reduction of the dosage of steroids and thereby reducing the risk of bacterial or other opportunistic infections.
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