Keywords
Neurosyphilis - onychoptosis - syphilis - syphilitic onychia
INTRODUCTION
Onychoptosis (from Greek onyx “nail” and ptôsis, “falling”) is a condition in which
part or all of the nail sheds periodically and falls off the finger; it can affect
one or more nails. Onychoptosis could happen as a result of fever, trauma, adverse
reaction to medications, and in systemic illnesses. It also occurs in secondary syphilis
infection where it is referred to “syphilitic onychia.”[1],[2] We discuss a case of 38-year-old man who presented with subacute bilateral retrobulbar
optic neuritis that was preceded with 3 months of persistent onychoptosis and he was
found to have neurosyphilis.
CASE SUMMARY
A 38-year-old man with history of high-risk sexual behavior presented with 6-week
progressing vision loss in both eyes. Eye examination showed severe decrease in visual
acuity in both eyes (20/400 in the right eye and 20/300 in the left) and mild-to-moderate
swollen disk bilaterally. Physical examination also revealed diffuse onychoptosis
[Figures 1] and [2] which patient developed 3 months prior to his presentation. The rest of the physical
examination was unremarkable. No other cutaneous or genital lesions were observed.
Onychoptosis prompted sending sexually transmitted disease (STD) panel, which revealed
positive syphilis immunoglobulin G (IgG)/immunoglobulin M (IgM) antibody. Rapid plasma
reagin (RPR) was reactive with titer of 1:256. Serum fluorescent treponemal antibody
absorption (FTA-ABS) was also reactive. The rest of STD panels including hepatitis
C and HIV tests were negative. Neuroaxis magnetic resonance imaging (MRI) revealed
equivocal T2 signal abnormality with contrast enhancement in the optic nerve bilaterally
consistent with bilateral retrobulbar optic neuritis. Cerebral spinal fluid (CSF)
testing showed normal glucose of 62 milligrams per deciliter (mg/dL) (reference range,
40–70), no red blood cells, elevated white blood cells of 32 cell per microliter (reference
range, 0–5) of which 96% were lymphocytes, and elevated total protein of 57mg/dL (reference
range, 15–45). CSF culture and gram stain were unremarkable. Given the presence of
pleocytosis and elevated total protein in CSF in the setting of active syphilis infection
with optic nerve involvement, the diagnosis of neurosyphilis was made. Patient was
treated with 4-million-unit aqueous penicillin G intravenously every 4h for 14 days.
On 1-month follow-up, onychoptosis completely resolved, visual acuity improved to
20/300 in the right eye and 20/100 in the left, and fundoscopy revealed normal optic
nerves bilaterally.
Figure 1: Diffuse onychoptosis involving all fingernails
Figure 2: Onychoptosis involving all fingernails of the right hand. Periungual tissue remains
intact
DISCUSSION
Syphilis, the “great imitator” of skin diseases, is a chronic systemic infectious
disease caused by spirochete Treponema pallidum. It is an STD that can also be transmitted vertically.[3],[4] It is estimated that there are 5.6 million new cases every year with highest rate
in Africa.[3] Centers for Disease Control and Prevention (CDC) reported that in 2018 there were
115,000 cases of syphilis and ~1300 cases of congenital syphilis in the United States
yielding 13.3% and 39.7% rate increase prospectively comparing with 2017.[5] Although syphilis is a reportable condition in the United States, rates of neurosyphilis
are not known partially due to surveillance definitions requiring data that are often
unavailable. However, neurosyphilis generally develops more in patients with HIV,
especially those who are untreated, have low CD4- counts, or have detectable HIV RNA
levels.[4]
There are multiple stages of syphilis: Primary (painless chancre appears after 9–90
days following acquisition of T. pallidum) which progresses if untreated to secondary syphilis (presents 12 weeks–12 months
after infection) which most often involves epithelial surfaces along with constitutional
symptoms and signs (fever, malaise, and generalized lymphadenopathy). Similar to primary
disease, the acute manifestations of secondary syphilis typically resolve spontaneously
as known as latent syphilis where there is serological proof of infection but no symptoms.
Syphilis will progress to tertiary disease in one-third of patients without treatment
roughly 20–40 years after primary infection.[6] Tertiary syphilis involves a severe and self-destructive immune response to a persistent
low-level burden of T. pallidum. This can present as neurosyphilis, cardiovascular syphilis, or late benign syphilis
(appears as granulomas, gummas, and psoriasiform plaques).[6],[7],[8]
It is important to emphasize that neurological symptoms can occur during any phase
of syphilis infection. Historically (in the pre-antibiotic era) neurosyphilis used
to occurs in 25%–35% of syphilis patients[4],[9] and symptomatic neurosyphilis developed in 4%–9% of patients.[7] There are no standard tests for the diagnosis of neurosyphilis; hence, the diagnosis
of neurosyphilis is based on clinical signs and symptoms and CSF findings.[4] CSF abnormalities include mild pleocytosis (10–400 cells per microliter) and elevated
protein concentrations (46–200mg/dL). Venereal Disease Research Laboratory test in
the CSF (CSF-VDRL) is highly specific but insensitive. When CSF-VDRL is negative,
the diagnosis of neurosyphilis can be made based on the presence of clinical signs
of neurosyphilis, reactive serologic test results, and abnormal CSF cell count and/or
protein.[9]
The eye is relatively uncommon site of syphilitic infection. However, syphilis can
affect almost any eye structure with posterior uveitis and panuveitis are the most
common place to be involved. When ocular syphilis occurs, it is often accompanied
by optic nerve involvement including perineuritis, papillitis, optic neuritis, and
retrobulbar neuritis (which is what happen in our case).[10],[11]
Despite its rarity, nail involvement in syphilis has been well established in medical
literature. It can be divided into syphilitic onychia (changes on nail plate) and
syphilitic paronychia (changes in periungual tissue). Syphilitic onychia involves
multiple manifestations including nail pitting, onycholysis (detachment of the nail
from its bed), onychogryphosis (one side of the nail to grow faster than the other),
onychomadesis (proximal separation of the nail plate from the nail matrix due to a
temporary cessation of nail growth), and onychoptosis (as in our patient) where in
syphilitic paronychia there is painful violaceous inflammatory indurations that appear
around nail folds, rarely transforming into abscesses.[2],[12],[13] Although ocular syphilis is treated with the same regimen used for neurosyphilis
(IV aqueous penicillin G 18–24 million units per day for 10–14 days), syphilitic onychia
is considered a form of secondary syphilis and hence the treatment would be shorter
and consists of single dose of benzathine penicillin G 2.4 million units given intramuscularly.[4],[9]
CONCLUSION
Syphilis can present with a wide range of clinical manifestations involving various
systems including eyes and nails. It is important for physicians to be aware of these
possible manifestations on syphilis infection. The presence of onychoptosis on physical
examination can help in reaching the diagnosis of syphilis where starting the proper
treatment early can stop any further potentially irreversible damage.
