Page 51 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

Overview of Primary and Secondary Vasculitides 27

responded to prednisone therapy. The most widely used diagnostic criteria of BD were
formulated by the International Study Group (ISG) [89] that included recurrent oral
ulcerations plus any two of genital ulceration, typical defined eye lesions, typical skin lesions,
or a positive pathergy. Recurrent oral ulcerations were categorized as minor aphthous, major
aphthous, and herpetiform ulcerations that recurred at least three times in a 12-month period.
Recurrent genital ulcerations were defined as aphthous ulceration and scarring. Eye lesions
were defined as anterior uveitis, posterior uveitis or cells in the vitreous on slit lamp
examination; and retinal vasculitis. Compatible skin lesions included erythema nodosum,
pseudofolliculitis, papulopustular lesions, and aceneiform nodules in post-adolescent patients
not receiving corticosteroids. A positive pathergy test of cutaneous hypersensitivity was
defined as positive when a sterile pustule developed after twenty four to forty-eight hours at
the site of a needle prick to the skin [90]. Although the usual onset of BD is in the third
or fourth decade of life, pediatric-onset patients have been described [91].
The neuropathological findings in BD in brain biopsies and postmortem examination have
been remarkably consistent among patients over the past several decades evidencing
perivascular cuffing of small meningovascular and parenchymal arteries and veins, rarely
medium-sized arteries displaying fibrinoid degeneration and recanalization, and examples of
venous thrombosis. Cortical venous sinus thrombosis (CVST) [92] in BD presents with
subacute or chronic onset of symptoms of isolated intracranial hypertension accompanied by
headache, blurred vision, and diplopia [93], and underlying necrotizing vasculitis. Venous
infarcts occur in up to 63% of those with CVST of other causes, but in only 6% of patients
with BD. The inflammatory cell infiltrates are generally comprised of lymphocytes, both T-,
and B-cells, macrophages, rarely plasma cells and eosinophils, with reactive astrocytosis and
microscopic gliosis in neighboring cerebral, cerebellar and brainstem white matter.
Matsumoto and colleagues [94] noted large vessel lesions in seven of eight patients age 31 to
56 years with BD, including saccular aneurysms of the sinus of Valsalva or aortic arch,
thoracic and abdominal aorta, pulmonary, femoral, and iliac arteries, and thrombotic
occlusions in the pulmonary vein and superior and inferior vena. Aortitis was noted
histologically in six of the eight patients that was active in one, scarred in six, and intermixed
in another. Active aortitis was characterized by intense infiltration of inflammatory cells in
the media and adventitia more frequently than in the interim with occasional giant cell
formation. Although anticoagulation would not be recommended for BD-related CVST, it
might be considered in association with arterial occlusions, with both venous and arterial
occlusive episodes warranting prompt consideration of corticosteroids alone or in association
with another immunosuppressant agent.

Cogan Syndrome
The first patient with Cogan syndrome of non-syphilitic interstitial keratitis (IK) was

reported by Mogan and Baumgartner [95], that of a 26-year-old man with recurrent pain,
spasm and redness of the left eye with photophobia, excessive tearing, and marked
conjunctival injection, followed by severe attack of dizziness, tinnitus, vertigo, nausea,
vomiting, ringing in the ears, profuse perspiration, and deafness. A diagnosis of recurrent
interstitial keratitis and explosive Meniere disease was made. Vestibuloauditory symptoms
were later described by Cogan [96]. Haynes and colleagues [97] set forth diagnostic criteria
for typical Cogan syndrome according to the definitions established in a review of 30 patients
seen at the National Eye Institute of the NIH by Cogan [96, 98, 99]. Symptoms of IK

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