Page 52 - The Vasculitides, Volume 1: General Considerations and Systemic Vasculitis

28 David S. Younger

developed abruptly and gradually resolved, associated with photophobia, lacrimation, and eye
pain which was unilateral or bilateral. Such symptoms tended to recur periodically for years
before becoming quiescent. Vestibuloauditory dysfunction was manifested by sudden onset of
Meniere-like attacks of nausea, vomiting, tinnitus, vertigo, and frequently progressive hearing
loss that characteristically occurred before or after the onset of IK. However within one to six
months of the onset of eye symptoms, auditory symptoms progressed to deafness over a
period of one to three months, certainly no longer than two years. With less than 100 reported
patients with this rare childhood and young adult disorder, the majority of reported patients
with typical Cogan syndrome have appeared as single case reports or patient series, often
without pathological confirmation or evidence of systemic vasculitis in a biopsy or at
postmortem examination. Early recognition of the diagnosis of childhood Cogan syndrome is
important in instituting corticosteroid therapy to preserve hearing especially when hearing
loss is a later occurrence. A combination of oral and intravenous corticosteroids may be
considered in children who partly but not fully improve. Most patients with Cogan syndrome
(58%) treated with corticosteroids derived a favorable response in both vestibuloauditory and
ophthalmologic manifestations, with the remainder demonstrating only ophthalmologic (23%)
or vestibuloauditory improvement (19%) alone [100]. Other therapies include methotrexate
(23%), cyclophosphamide (10%), azathioprine (5%), entanercept (3%), hydroxchloroquine
(2%), and IVIg (2%). Surgical cochlear implantation can led to objective and subjective
benefits with improved hearing.

Recognition of Secondary Vasculitides

Cryoglobulinemic Vasculitis

The presence in the serum of one or more immunoglobulins (Ig) that precipitate below
core body temperatures and redissolve on rewarming is termed cryoglobulinemia [100, 101].
Wintrobue and Buell [102] described the first patient with cryoglobulinemia, that of a 56-
year-old woman who presented with progressive frontal headache, left face and eye pain; and
right shoulder, neck and lumbar discomfort after a bout of shingles. This was followed by
Raynaud symptoms, recurrent nosebleeds, exertional dyspnea and palpitation, and changes in
the eye ground attributed to central vein thrombosis. Postmortem examination showed
infiltrating myeloma of the humerus and lumbar vertebra, and splenic enlargement. A unique
plasma protein was detected that spontaneously precipitated with cold temperature and
solubilized at high temperature that differed from Bence-Jones proteinuria of other myeloma
patients. Brouet and coworkers [103] provided modern classifications of cryoglobulinemia
among 86 patients that included type 1, composed of a single monoclonal Ig; and types II and
III as mixed cryoglobulinemia (MC), composed of different Ig, with a monoclonal component
in type II, and polyclonal Ig in type III. In the absence of well-defined disease the presence of
MC was termed “essential”. Since recognition of hepatitis C virus (HCV) infection in patients
with MC [104, 105], and the recognition of the high rate of false-negative serological tests in
type II MC [106], it became evident that HCV was associated in most patients with MC.
Cryoglobulinemic vasculitis is characterized by the classical triad of purpura, weakness and
arthralgia, frequent multiple organ involvement, and infrequent late lymphatic and hepatic

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