Download Herpetic Whitlow of the Toe: An Unusual Manifestation of Infection

196
Brief Reports
Herpetic Whitlow of the Toe: An Unusual Manifestation
of Infection with Herpes Simplex Virus Type 2
Herpetic whitlow is a painful infection of the periungal region
of the finger, caused by herpes simplex virus (HSV). The term
‘‘whitlow’’ is derived from the Scandinavian term whichflaw;
which refers to the sensitive area around a nail, and flaw means
‘‘crack.’’ A damaged cuticle is thought to provide the usual portal
of entry. With the exception of the occupational exposure of health
care workers, the source of infection is usually autoinoculation; in
children the source of infection is primary infection of the oropharynx with HSV-1, and in adults the source of infection is primary
genital herpes infection with HSV-2 that has spread to a finger
[1]. We describe an unusual variation on this theme, a
herpetic whitlow of the toe caused by HSV-2.
CID 1998;26 (January)
tions to take oral cephalexin. Results of gram staining and bacterial
culture of the aspirated fluid were negative.
The patient was readmitted to the hospital 2 days later because of
severe pain, swelling, and blister enlargement. The blister had enlarged
in a circumferential fashion, and hemorrhagic discoloration was evident
at the proximal margin (figure 1). The patient provided a history of a
similar but milder episode of coincidental dysuria and toe swelling that
had occurred 7 months earlier. The blister was reaspirated, and the
results of direct fluorescent antibody testing of the aspirate were positive
for HSV-2. Therapy with valacyclovir was begun. Cervical cultures
were positive for Chlamydia trachomatis and negative for HSV and
Neisseria gonorrhoeae. Results of tests for HIV and syphilis were
negative. The patient and her husband were treated with azithromycin
for C. trachomatis infection. The herpetic whitlow slowly resolved in
response to treatment with valacyclovir. Two months later, the patient
Figure 1. Herpetic whitlow of
the toe caused by herpes simplex
virus type 2 in a 28-year-old female patient.
A 28-year-old woman developed urinary frequency and intermittent
suprapubic pressure, without systemic symptoms. Findings on physical
examination were normal. Dipstick testing of urine revealed nitrates,
erythrocytes, and leukocytes. Trimethoprim-sulfamethoxazole (TMPSMZ) was prescribed for suspected urinary tract infection. Four days
later, the pelvic symptoms had not abated, and there was pruritus in
the second toe of the right foot. This rapidly became painful and was
associated with local edema, erythema, and blister formation on the
dorsum of the toe. Oral cephalexin was prescribed for treatment of
possible cellulitis, but the severity of the pain necessitated hospitalization 1 day later.
On admission to the hospital, the patient complained of severe pain
in the toe radiating to the entire forefoot; she also complained of mild
nausea. Her temperature was 37.57C. The affected toe was swollen
with a dorsal blister, and mild erythema and edema extended into the
forefoot. The physical examination findings were otherwise normal.
Findings on a right-foot radiograph were normal. Clear yellow fluid
was aspirated from the blister, and therapy with iv cefazolin was instituted for treatment of possible bacterial cellulitis. After 2 days, slight
improvement was evident, and the patient was discharged with instruc-
Reprints or correspondence: Dr. Laurence J. Egan, Mayo Clinic and Foundation, 200 First Street S.W., Rochester, Minnesota 55905.
Clinical Infectious Diseases 1998;26:196–7
q 1998 by The University of Chicago. All rights reserved.
1058–4838/98/2601–0037$03.00
developed erythema and pain in the same toe, and therapy with valacyclovir was again effective in resolving the condition. Mild postherpetic neuralgia responded to treatment with low-dose amitriptyline.
HSV-1 infection of the toe has been described [2], but ours is the
first reported case of herpetic whitlow of the toe caused by HSV-2.
For our patient, the severity of pain, the history of a stereotypically
similar episode, the negative bacterial culture, and the lack of response
to antibacterial therapy prompted testing for herpesvirus infection. Although the organism was not isolated from the patient’s cervix after
initiation of antiherpetic chemotherapy, it is likely that the prodrome
of pelvic pain and urinary frequency experienced by this patient was
due to herpes cervicitis. This second episode of coincidental dysuria
and toe ‘‘cellulitis’’ could have been reactivation of a primary infection
acquired 7 months earlier. Although autoinoculation of female genital
herpes to a toe is possible, an alternative explanation exists: zosteriform
neural transmission from infected sacral ganglia [3]. In this model,
reactivation of latent HSV in sacral sensory ganglia leads to recurrent
herpetic eruptions in the corresponding dermatomes, which in our case
would be those originating from the lower lumbar or upper sacral level.
Therapy with oral acyclovir or related antiherpetic drugs (valacyclovir
or famciclovir) may be useful if recurrences are problematic [4]. Clinicians should consider the diagnosis of herpes simplex when painful
mucocutaneous lesions recur in the same location.
Laurence J. Egan, Jon M. Bylander, David C. Agerter,
and Randall S. Edson
Mayo Clinic and Foundation, Rochester, Minnesota
CID 1998;26 (January)
Brief Reports
197
References
1. Oxman MN. Herpes simplex viruses and human herpesvirus 6. In: Gorbach
SL, Bartlett JG, Blacklow NR, eds. Infectious diseases. Philadelphia:
W.B. Saunders, 1992:1667 – 700.
2. Feder HM Jr, Geller RW. Herpetic whitlow of the great toe. N Engl J Med
1992; 326:1295 – 6.
3. Slavin HB, Ferguson JJ. Zoster like eruptions caused by the virus of herpes
simplex. Am J Med 1950; 8:456 – 67.
Unusual Outcome of Disseminated Candidiasis Treated
with Fluconazole: A Matter of Pharmacokinetics?
Our patient was successfully treated with a 5-week course of fluconazole for candidemia with pulmonary foci, but this treatment failed
to prevent the occurrence of sacroiliitis. A lack of bioavailability is
an unlikely explanation for this failure. Moreover, a fluconazoleteicoplanin drug interaction has not previously been described. Another hypothesis is that this strain of C. albicans was resistant to
fluconazole, but this could not be proved since the susceptibility of
this strain to this drug was not tested. Primary resistance of C. albicans
to fluconazole is rare in a patient who has not previously received
this drug. Furthermore, there is no clear MIC predictive of a treatment
failure for patients with systemic candidiasis [3].
Thus, the outcome in our case is suggestive of impaired osteoarticular activity of fluconazole. In vivo penetration of fluconazole
into synovial fluid was shown to be good [4]. Although the sacroiliac joint is diarthrodial, adjacent bone is frequently involved in
pyogenic sacroiliitis [5]. Bone involvement in our patient was
evidenced by the irregularity of the bony margins on a CT scan.
Pharmacokinetic data obtained for volunteers showed that mean
concentrations ({SD) of fluconazole in bone 90 minutes after an
infusion (5 mg/kg) are only 1.24 { 0.29 mg/g compared with 7.81
{ 0.46 mg/g in lung [6]. These data suggest that the standard
fluconazole dose of 400 mg/d could be problematic in the treatment
of osteomyelitis and therefore provide a possible explanation for
the poor treatment outcome in our case. The low bone penetration
can be offset by using a higher dosage of fluconazole because its
toxicity is lower than that of other antifungal agents.
Sporadic case reports suggest that the standard dosage of fluconazole
(or even a lower dosage) is successful for treating osteoarticular infections [2, 4, 7–9]. Nevertheless, failure of fluconazole therapy (400 mg/
d) for sternal osteomyelitis due to C. albicans has been reported [10].
Osteoarticular infection due to Candida species may be a sequela
of any antifungal therapy in patients with fungemia. Such infections
remain rare and may occur more than a year after an episode of
candidemia [11]. It is therefore still unknown whether fluconazole
is as effective as amphotericin B for preventing late osteoarticular
complications; if it is as effective, the appropriate dosage must be
determined.
Thus, we would like to emphasize the following points. First, a
dosage of fluconazole that is higher than the standard dosage of 400 mg/
d should be considered in the treatment of candidemia or osteoarticular
infections due to C. albicans in future clinical trials. Second, the performance of tests such as a technetium radionuclide scan should be discussed in each patient’s case so that latent osteoarticular localizations
can be detected before treatment for candidemia is stopped. Third, our
observation emphasizes the need to perform pharmacokinetic analysis
and susceptibility testing for patients with candidemia.
Fluconazole is considered to be a safe and effective alternative
to amphotericin B for treating nonneutropenic patients with Candida
albicans candidemia [1]. Various types of candidiasis, including osteoarticular infections, have been successfully treated with fluconazole
[2]. We report a case of C. albicans sacroiliitis that occurred despite
healed candidemia with pulmonary foci in a patient treated with fluconazole.
A 28-year-old woman was admitted to the hospital in June 1994 for
the treatment of chronic arthritis of a hip prosthesis due to multiresistant
staphylococci. Teicoplanin was administered parenterally through a
central venous catheter. Eight days later, she became febrile and complained of chest pain. Her WBC count was 12,600/mL, and her Creactive protein level was 102 mg/L. Blood cultures yielded C. albicans
that was susceptible to 5-fluorocytosine (5-FC), amphotericin B, and
ketoconazole. Findings on a roentgenogram of the thorax, an electrocardiogram, an echocardiogram, and a pulmonary angiogram were normal.
A thoracic CT scan revealed pulmonary nodular foci that were suggestive of septic emboli.
The central venous catheter was removed, and the patient received
iv fluconazole therapy (400 mg/d) for 5 weeks. Her clinical condition
improved rapidly. Three weeks after fluconazole therapy was stopped,
she complained of pain in her left buttock. Blood cultures were negative. A CT scan of the sacroiliac revealed sacroiliitis. CT scan–guided
needle aspiration of the sacroiliac joint was performed, and culture of
the aspirates yielded C. albicans. The susceptibility of the isolates to
antifungal agents was unchanged.
The patient was given iv therapy with amphotericin B (1 mg/[kgrd])
and 5-FC (150 mg/[kgrd]) for 3 months. Itraconazole therapy (400
mg/d) was added to the regimen during the first month. The patient’s
clinical condition improved over this period. A CT scan revealed that
the lesions were unchanged. Treatment with oral fluconazole (800
mg/d) and 5-FC (150 mg/[kgrd]) was continued until October 1995,
when a technetium radionuclide scan did not reveal uptake in the
sacroiliac joint and the candidal serology became negative. At a followup visit, it was determined that therapy with fluconazole had been well
tolerated and there was no hepatic dysfunction. Follow-up examinations
in October 1996 and March 1997 showed that there had been no
relapse.
Reprints or correspondence: Dr. Jean-Francois Faucher, Service des Maladies Infectieuses et Tropicales, Hôpital Gui de Chauliac, 34 295 Montpellier
Cedex 5, France.
Clinical Infectious Diseases 1998;26:197–8
q 1998 by The University of Chicago. All rights reserved.
1058–4838/98/2601–0038$03.00
4. Gill JM, Bryant HE. Oral acyclovir therapy of recurrent herpes simplex
virus type 2 infection of the hand. Antimicrob Agents Chemother 1991;
35:382 – 3.
Jean-François Faucher, Marie-Marthe Thiébaut,
Jacques Reynes, and François Janbon
Service des Maladies Infectieuses et Tropicales, Hôpital Gui de
Chauliac, Montpellier, France