Faculty Bibliography

There have been significant advances in the understanding of the vasculitides in the past several years, leading to more precise classification and nosology. Ophthalmologic manifestations may be the presenting feature of and a clue to the diagnosis of vasculitis, or develop in the course of the illness owing to a common disease mechanism. Precise diagnosis and prompt treatment prevents short- and long-term ophthalmologic sequela.

The epidemiology of vasculitis has witnessed extraordinary advances in the past decade influenced by the worldwide increased recognition and accurate classification and diagnosis of the vasculitides, and insights brought by genome-wide association studies and online genetic biological repositories that permit researchers to freely access a wide array of genetic and clinical resources that contribute to the understanding of the heritable factors of the systemic vasculitides. This article reviews the current knowledge of the epidemiology of vasculitides in different global regions.

The diagnosis of primary central and peripheral nerve vasculitides should be established with certainty if suspected before commencing potent immunosuppressive therapy. The aim of induction therapy is to rapidly control the underlying inflammatory response and stabilize the blood-brain and blood-nerve barriers, followed by maintenance immunosuppression tailored to the likeliest humoral and cell-mediated autoimmune inflammatory vasculitic processes.

"Giant cell arteritis (GCA) is a chronic, idiopathic, granulomatous vasculitis of medium and large arteries comprising overlapping phenotypes of cranial arteritis and extracranial GCA. Vascular complications are generally due to delay in diagnosis and initiation of effective treatment. Advancements in MRI and MR angiography, computed tomography angiography, 18fluoro-deoxyglucose/PET, and color duplex ultrasonography have led to improved diagnosis. Corticosteroids are the mainstay of therapy in GCA; however, their use is associated with predictable and occasionally serious side effects. Biological agents are effective and safe corticosteroid-sparing agents in treating GCA. This article reviews the epidemiologic, clinicopathologic features, diagnosis, and treatment of GCA."

Autoimmune encephalitis is a severe inflammatory disorder of the brain with diverse causes and a complex differential diagnosis. Recent advances in the past decade have led to the identification of new syndromes and biological markers of limbic encephalitis, the commonest presentation of autoimmune encephalitis. The successful use of serum and intrathecal antibodies to diagnose affected patients has resulted in few biopsy and postmortem examinations. In those available, there can be variable infiltrating inflammatory T cells with cytotoxic granules in close apposition to neurons, consistent with an inflammatory autoimmune basis, but true vasculitis is rarely seen. The exception is Hashimoto encephalopathy.

"Neuroimaging plays a vital role in the diagnosis of primary and secondary vasculitic disorders. There multiple neuroimaging options available to accurately describe the underlying clinical deficits of involved cases. Noninvasive neuroimaging modalities provide less risk and when interdigitated, form the basis for a more conclusive understanding of the disease process. There are instances in which invasive cerebral angiography may be needed to image the intricate and at times, small involved vessels. Neuroradiologists should be included in the multidisciplinary team of physicians caring for patients with vasculitides and in research to provide more sensitive and safe modalities for accurate diagnosis."

Granulomatous inflammation, the prototypical histopathology of adult and childhood vasculitis, is characterized by inflammation of blood vessels accompanied by giant cells and epithelioid cells in the walls of cerebral vessels ranging from small leptomeningeal veins to large named cerebral arteries. Headache, hemiparesis, mental changes, abnormal cerebrospinal fluid protein content, and pleocytosis are suggestive features that warrant brain and leptomeningeal biopsy to make the diagnosis certain and begin cytotoxic therapy to improve outcome.

Systemic and localized vasculitis affects the skin and subcutis, due to large vascular beds and hemodynamic factors, such as stasis in lower extremities, and environmental influences, as occur in cold exposure. Initial cutaneous manifestations of vasculitides include diverse and dynamic patterns of discoloration, swelling, hemorrhage, and necrosis. One-half of affected patients present with localized, self-limited disease to the skin without any known trigger or associated systemic disease, known as idiopathic cutaneous leukocytoclastic vasculitis. Skin biopsy and dermatopathology contribute relevant information; however, they require correlation with clinical history, physical examination, and laboratory findings to reach an accurate diagnosis.

There has been extraordinary research in the blood-brain barrier. Once considered a static anatomic barrier to the traffic of molecules in and out of the central nervous system when fully developed in adults, the blood-brain barrier is now known to be not only fully functional in development but also vital in cerebrovascular angiogenesis. Blood-brain barrier breakdown has been recognized as an important factor in a variety of primary neurologic diseases; however, such disturbances have yet to be critically analyzed. This article reviews the history, neurodevelopment, ultrastructure, function, and clinicopathologic correlation and relevance to central nervous system vasculitis.