FINAL DIAGNOSIS: MICROVASCULITIS ASSOCIATED WITH SYSTEMIC LUPUS ERYTHEMATOSUS
Subsequently, additional serology showed elevated ANA (1/8000 speckled pattern) and positive antiphospholipid antibodies; CSF oligoclonal bands were atypical with IgG 0.95 and albumin 1.13. A renal biopsy demonstrated lupus nephritis and numerous tubulo-reticular inclusions (TRIs) in endothelium.
After the diagnosis of SLE, aggressive immunomodulating treatment was instituted however the patient deteriorated and developed status epilepticus refractory to treatment (probably cerebral lupus), had repeated episodes of sepsis and respiratory failure, and died six months after admission of multiple organ dysfunction. An autopsy was not performed.
Causes of peripheral nerve vasculitis include polyarteritis nodosa, Churg-Strauss angiitis, Wegener's granulomatosis , vasculitis associated with rheumatoid arthritis and primary vasculitis of peripheral nerve; all of which affect, with rare exceptions, muscular vessels in the epineurium in the 75-300 um diameter range, where necrosis of the wall is easier to detect. In the endoneurial compartment the vasculature consists of microvessels in the range of 9-22 um in diameter, devoid of mucularis. Since here the mere demonstration of perivascular lymphocytic cuffing is not evidence of vasculitis and because a dense focal inflammatory infiltrate may eclipse a microvessel, the diagnosis of vasculitis is fraught with uncertainty. Our criteria for the diagnosis of necrotizing vasculitis comprise either fibrinoid change or polymorphonuclear cell wall infiltrate plus karyorrhexis. In a consecutive series of nearly 800 nerve biopsies we identified 59 cases of angiitis of which, by using serial sections, oil immersion microscopy of paraffin and plastic sections, and electron microscopy, three were found to affect endoneurial microvessls (two patients with SLE and one patient with AIDS), associated with numerous TRIs in the cytoplasm of endothelial cells. These inclusions (also known as undulating tubules) which were not demonstrable in angiitis affecting larger epineurial vessels, are distinctive anastomosing tubules 20-30 nm in diameter (Fig 6) most often seen in endothelial cells but also in lymphocytes. Described about 30 years ago in lupus nephritis they have subsequently been documented in many systemic and organ-specific conditions such as autoimmune diseases, viral infections and neoplasia. In neuromuscular diseases the observation of TRIs in endomysial vessels is helpful for it segregates the dermato-lupus myositis complex (where capillary destruction is determinant of myonecrosis) from the other inflammatory myopathies; in peripheral nerve they have been described in localized inflammatory neuropathy (1), in polyneuropathy complicating SLE (2) and in nerve biopsies of patients with AIDS (3). Tubulo-reticular inclusions arise from the nuclear membrane and can be induced experimentally in tissue cultures by exposure to interferon. Noteworthy is the association of microvascular damage in endoneurium and TRIs in endothelium in that it seems restricted to patients with SLE and AIDS. Interestingly, high levels of serum interferon are reported in active SLE, and indicate a worse prognosis in AIDS.
Note: This case was discussed at the 1997 meeting of the Canadian Association of Neuropathologists in Ottawa at the unknown slide seminar.
Contributed by Juan M. Bilbao, MD.
University of Toronto, Department of Pathology, St. Michael's Hospital, Toronto, Ontario, Canada, M5B 1W8