Peripheral Signs of Endocarditis

Roth's spots: Oval- shaped, white- centered hemorrhages
present on the retina of some patients with
infective endocarditis.



Roth's spots are named for Swiss pathologist
Moritz Roth (1839-1914), who, in 1872, described
white- centered hemorrhages on the funduscopic examinations
of patients with sepsis.3 In 1878, the spots were
found to consist of "round or elongated white foci
occurring close to the nerve head . . . single or multiple
and occasionally surrounded by a hemorrhagic ring."4
In 1931, these hemorrhages were associated with bacterial
endocarditis and described as "pathognomonic
canoe- shaped linear hemorrhagic spot(s) with a light
central area."
Pathogenesis
The pathogenesis of Roth's spots is unclear but is
thought to involve several potential mechanisms. In his
original studies, Roth believed that the spots represented
embolic bacterial infiltrates producing localized
retinal abscesses.4,5 The emboli were presumed to have
originated from the endocardium. The currently
accepted explanation involves anoxia that causes a sudden
increase in venous pressure, which results in capillary
rupture in the inner retinal layers.5 This rupture
results in extravasation of blood and formation of a
fibrin-platelet plug.
Diagnosis and Differential Diagnosis
Although Roth's spots have been classically associated
with endocarditis, they have also been found in many
other conditions, including hematologic malignancies,
connective tissue diseases, vasculitides, anemia, hypertension,
diabetes mellitus, HIV disease, and intracranial
hemorrhage.5 In the patient who has an otherwise typical
presentation of endocarditis, Roth's spots may be
helpful in the diagnosis; however, when nonspecific
symptoms are present, Roth's spots should alert the
physician to other possible systemic diseases.
Osler's nodes: Painful, erythematous nodules most
commonly found on the pads of the fingers and toes
of some patients with infective endocarditis.

Osler's nodes are named for Canadian
physician and educator Sir William Osler (1849-1919),
who, in 1893, described painful, erythematous nodules
on the pads of the fingers and toes in patients with
endocarditis.6 Several other clinicians predated Osler
in the description of these nodules,7,8 but he placed thegreatest significance upon the nodules and was the first to acknowledge their utility in the diagnosis of endocarditis.

Pathogenesis
Like that of Roth's spots, the pathogenesis of Osler's
nodes is unclear. One theory contends that these nodules
are the result of septic microemboli originating
from an endocardial valvular lesion, and that pathogenic
organisms can sometimes be recovered from
aspiration of these lesions.6,7 Another theory holds that
the nodes are caused by an immunologically-mediated
vasculitis caused by circulating immune complex deposition
in the skin.7 A fair amount of evidence supports
both explanations, therefore, the actual pathogenesis
of Osler's nodes remains a mystery.
Diagnosis and Differential Diagnosis
Osler's nodes are usually associated with subacute
bacterial endocarditis and appear late in the disease
course. However, the sign may also be found in other
conditions, including bacteremia, septic endarteritis,
typhoid fever, gonococcemia, and systemic lupus erythematosus.
6,7 Osler's nodes appear suddenly, are quite
painful, and are sometimes heralded by premonitory
paresthesias. Although generally located on the fingers
and toes, the nodes may be present on the forearms,
mucous membranes, flank, or trunk. With appropriate
antibiotic therapy, Osler's nodes resolve within 1 to
3 days and leave no sequelae.
Janeway lesions: Nontender, erythematous and nodular
lesions most commonly found on the palms and
soles of some patients with infective endocarditis.

Janeway lesions are named for noted
American physician Edward G. Janeway (1841-1911),
who, in 1899, described "numerous small hemorrhages
with slight nodular character in the palms of the hand
and soles of the feet . . . in malignant endocarditis."9 In
1906, Emanuel Libman, a student of Janeway, coined
the term "Janeway lesion," and went on to further
study these lesions and affirm their association with
infective endocarditis.

Pathogenesis
The pathogenesis of Janeway lesions is also unclear.
Some authors believe that these lesions are necrotic
microabscesses with an inflammatory infiltrate that
involves the dermis but not the epidermis.9,10 Other
authors believe that the lesions are the result of septic
microemboli that originate from the endocardium, a
fact that has been substantiated by histopathologic
studies in the literature.10 -12
Janeway Lesions Compared with Osler's Nodes
Janeway lesions are usually associated with acute
bacterial endocarditis.11 They frequently have an irregular
outline, are erythematous and nodular, and sometimes
appear hemorrhagic. They have been confused
with Osler's nodes; however, two important distinctions
exist. First, Janeway lesions usually occur on the palms
and soles, not on the pads of the fingers. Second,Janeway lesions are not tender, whereas Osler's nodes
are often exquisitely tender, which is the most compelling
difference between these two signs.
Splinter hemorrhages: Small, linear hemorrhages
under the nails that are usually asymptomatic and
found in some patients with infective endocarditis.

Splinter hemorrhages were originally described in
1920 in patients with endocarditis as "minute petechiae,
in the form of a vivid linear splash of red at the side of
the bed of a fingernail."13 In 1926, this association was
affirmed by Blumer,14 and in recent years, various other
authors have described splinter hemorrhages in other
conditions, including trichinosis, mitral stenosis, psoriasis,
onychomycosis, vasculitis, meningococcemia, and
trauma.13,15,16 Splinter hemorrhages have also been described
in healthy individuals,16 patients on hemodialysis,
and individuals who perform manual labor.15
Splinter hemorrhages are usually less than 2 to
3 mm long and lie under the distal one third of the
nail, traveling outward as the nail grows.13 Early in development,
the hemorrhages are reddish-brown; but with
maturity, they become brown to black, a process that
takes 1 to 2 days. Splinter hemorrhages are usually
asymptomatic, but they may be painful or tender to palpation.
They are caused by engorgement of capillaries
under the nail, but the etiology of the hemorrhages is
unclear. Potential mechanisms include digital vasospasm,
embolic events, and local factors that promote
capillary engorgement.
DIAGNOSIS OF ENDOCARDITIS
Because the diagnosis of endocarditis is often difficult,
many researchers have sought to standardize the
process and simplify the task. In recent years, two sets
of criteria for the diagnosis of endocarditis have been
described. The guidelines offered by Von Reyn et al17
rely on strict clinical criteria, including positive blood
cultures, murmurs, fever, and peripheral manifestations,
and ignore the importance of echocardiographic
data and a history of intravenous drug use as a risk factor
for endocarditis. The more recent Duke criteria
rely on clinical manifestations as well, but these guidelines
also factor in echocardiographic data and history
of intravenous drug use in the diagnosis of endocarditis.
18 The Duke guidelines also incorporate a system of
major and minor criteria that make them more specific
and sensitive than the Von Reyn criteria. Interestingly,
whereas Janeway lesions, Osler's nodes, and Roth's
spots are considered minor elements in the Duke criteria,
splinter hemorrhages are not included within the
Duke guidelines. Another recent study19 has suggested
modifications to the Duke criteria, including adding
splinter hemorrhages to the list of minor elements
because they were found to be more common than the
other peripheral phenomena in patients with endocarditis.
Despite the criteria outlined above, the peripheral
signs are seen less frequently today in patients with
endocarditis.1 This decrease in frequency has been
attributed to several causes, including earlier diagnosis
of endocarditis, earlier institution of antibiotic therapy,
and possible physician inexperience in recognizing the
signs.6 A recent study examining 135 cases of endocarditis
over 9 years noted that the peripheral manifestations
were fairly uncommon, with Osler's nodes present
in 6.7% of cases, Janeway lesions present in 2.2% of
cases, Roth's spots present in 3% of cases, and splinter
hemorrhages present in 39% of cases.2 By contrast,
murmurs were found in 94% of these cases, and fever
was found in 87% of cases.
SUMMARY
The peripheral manifestations of endocarditis are
venerable signs that may be useful adjuncts to the diagnosis
of endocarditis. With advances in technology and
treatment, the signs have become less common, but they
nevertheless remain a subject for intense scrutiny.