Acanthosis Nigricans: A New Manifestation of Insulin Resistance in ...

1 MARCH
Correspondence
Acanthosis Nigricans:
A New Manifestation
of Insulin Resistance
in Patients Receiving
Treatment with Protease
Inhibitors
Figure 1.
inhibitors.
Acanthosis nigricans in the axilla of a patient receiving treatment with protease
Sir—Dubé [1] and Thiébaut et al. [2]
have published interesting articles describing
insulin resistance in patients
with HIV infection who are receiving
treatment with protease inhibitors. Recently,
an increasing number of papers
have been published which relate treatment
with protease inhibitors to the appearance
of insulin resistance, diabetes,
hyperlipidemia, and anomalies in the distribution
of corporal fat [3]. We describe
a patient with HIV infection who, after
beginning treatment with protease inhibitors,
developed insulin resistance, diabetes
mellitus, and acanthosis nigricans.
To our knowledge, such a case has not
been described in the medical literature.
The patient was a 36-year-old man
who had had HIV infection diagnosed 5
years before presentation. He had received
treatment with ritonavir, zidovudine,
and didanosine for 19 months; this
regimen was then changed to with nelfinavir,
saquinavir, stavudine and nevirapine,
which he received for 17 months.
Diabetes mellitus was diagnosed 9
months after the patient started treatment
with ritonavir. At the time the patient
presented to our clinic, he was
asymptomatic. Findings of a physical examination
were as follows: height, 187
cm; weight, 91 kg; body mass index, 26
kg/m 2 ; loss of facial and gluteal fat, increase
of abdominal fat; and a velvetaspect
hyperpigmentation in the axillas
and elbows (figure 1). Other physical examination
findings were normal. Complementary
laboratory studies were performed,
for which the values were as
follows: blood glucose, 229 mg/dL; total
cholesterol, 145 mg/dL; high-density lipoprotein
cholesterol, 29 mg/dL; triglycerides,
174 mg/dL; CD4 count, 361 cells/
mL; and virus load, 236,000 copies/mL. A
test of pancreatic reserve with glucagon
was performed; the basal C-peptide level
was 5.5 ng/mL, and after stimulus, it was
12 ng/mL. At that time, the patient had
a basal blood glucose level of 259 mg/dL
and an insulin level of 41.10 mg/dL. The
insulin sensitivity score, as determined by
use of the Quantitative Insulin Sensitivity
Check Index [4] was 0.25, which indicates
high insulin resistance. The result
of a cutaneous biopsy of the axilla was
compatible with acanthosis nigricans.
The patient began treatment with oral
hypoglycemic drugs, which resulted in
good control of blood glucose levels.
Acanthosis nigricans is a cutaneous
marker of insulin resistance, although, in
a few cases, it has also been associated
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716 • CID 2002:34 (1 March) • CORRESPONDENCE

with malignant diseases, receipt of certain
medications, and uncommon illnesses
[5]. It is characterized by the appearance
of papillomatosis with hyperpigmented
and hyperkeratosis plaques that have a
velvet texture and a grayish-brown coloration.
These lesions are distributed
symmetrically and affect flexural areas,
including the neck, axilla, groin, antecubital
and popliteal fossa, and the periumbilical
region; occasionally, they can
affect the mucous areas [6]. It is believed
that hyperinsulinemia favors the bond
between insulin and growth factor receptors
similar to insulin receptors, which
stimulate the proliferation of keratinocytes
and fibroblasts in the dermis. The
pathologic diagnosis includes hyperkeratosis
and slight acanthosis with dermal
papillomatosis.
Insulin resistance appears in 61% of
patients with HIV infection who are receiving
treatment with protease inhibitors
[7], but acanthosis nigricans has only
been described as associated with HIV
infection in 1 patient with opportunistic
infections [8]. It has not, to our knowledge,
been described as associated with
protease inhibitor treatments, although it
is not infrequent in other situations of
insulin resistance [9]. Acanthosis nigricans
should be considered a new manifestation
of insulin resistance syndrome
in patients with HIV infection who are
receiving treatment with protease inhibitors;
the skin of such patients should be
carefully examined.
Susana Mellor-Pita, Miguel Yebra-Bango,
Joaquín Alfaro-Martínez, and Emilio Suárez
Servicio de Medicina Interna 1, Clinica Puerta
de Hierro Universidad Autónoma de Madrid,
Madrid, Spain
References
1. Dubé MP. Disorders of glucose metabolism in
patients infected with human immunodeficiency
virus. Clin Infect Dis 2000; 31:1467–75.
2. Thiébaut R, Daucourt V, Mercié P, et al. Lipodystrophy,
metabolic disorders, and human
immunodeficiency virus infection: Aquitaine
cohort, France, 1999. Clin Infect Dis 2000;
31:1482–7.
3. Carr A, Samaras K, Burton S, et al. A syndrome
of peripheral lipodystrophy, hyperlipidaemia
and insulin resistance in patients receiving
HIV protease inhibitors. AIDS 1998;
12:F51–58.
4. Katz A, Nambi SS, Mather K, Baron AD, et
al. Quantitative insulin sensitivity check index:
a simple, accurate method for assessing
insulin sensitivity in humans. J Clin Endocrinol
Metab 2000; 85:2402–10.
5. Houpt KR, Cruz PD. Acanthosis nigricans. In:
Freedberg IM, Eisen AZ, Wolff K, et al., eds.
Fitzpatrick’s dermatology in general medicine.
5th ed. New York: McGraw-Hill, 1999:
2121–6.
6. Flier JS. Metabolic importance of acanthosis
nigricans. Arch Dermatol 1985; 121:193–4.
7. Walli R, Herfort O, Gerlinde M, et al. Treatment
with protease inhibitors associated with
peripheral insulin resistance and impaired
oral glucose tolerance in HIV-1 infected patients.
AIDS 1998; 12:F167–73.
8. Maltez, F, Martins T, Morgado A, Proença R.
Será a canthosis nigricans uma nova manifestação
cutâtanea de infecção pelo vírus da
imunodeficiência humana? Acta Médica Portuguesa
1997; 10:493–5.
9. Stuart CA, Pate CJ, Peters EJ. Prevalence of
acanthosis nigricans in an unselected population.
Am J Med 1989; 87:269–72.
Reprints or correspondence: Dr. Susana Mellor-Pita, Servicio
de Medicina Interna 1, Clinica Puerta de Hierro Universidad
Autónoma de Madrid, San Martín de Porres, 4, 28035 Madrid,
Spain.
Clinical Infectious Diseases 2002; 34:716–7
2002 by the Infectious Diseases Society of America. All
rights reserved. 1058-4838/2002/3405-0027$03.00
Seroreversion from
Hepatitis C after
Needlestick Injury
Sir—We read with great interest the case
report by Morand et al. [1], which described
the lack of seroconversion after
early treatment of acute hepatitis C following
needlestick injury, despite the
normal cellular and humoral responses
of the host. Because few reports are available
on the course of the immune response
to hepatitis C virus (HCV) after
early treatment of acute hepatitis C, we
present a case report that may contribute
to discussion of this topic.
In January 1997, a 34-year-old nurse
who had tested negative for both HIV
and HCV sustained a superficial wound
caused by a venipuncture needle. The donor
patient was HIV negative, was infected
with an HCV isolate of genotype
1a (identified by Inno-LiPA HCV II;
InGeN), and had a high virus load (7.00
log 10 copies/mL) detected in serum samples
(Cobas Monitor HCV; Roche Diagnostic
System).
Follow-up examination of the nurse
included determination of the alanine
aminotransferase (ALT) level, monthly
testing for HCV RNA by the use of reverse-transcriptase
PCR (Cobas Amplicor
HCV; Roche Diagnostic System),
and anti-HCV testing with the use of 2
third-generation ELISAs (AxSYM HCV,
version 3.0 [Abbott Laboratories], and
Monolisa HCV Plus [Bio-Rad]). Specific
antibody response was analyzed by strip
immunoassay (SIA); analysis was done in
1997, by use of the Deciscan assay (Bio-
Rad), and then retrospectively, by use of
the RIBA HCV 3.0 assay (Chiron). The
results of these analyses are shown in table
1.
During the first month after exposure
(month 1), HCV RNA was detected in
the nurse’s serum, and her ALT level increased
to up to 3.5 times greater than
the normal level. The nurse was found
to have the same HCV genotype as the
donor patient. Treatment with IFN-a
(3 million U given 3 times per week for
3 months) was initiated immediately.
Treatment continued pragmatically for a
total of 6 months, because HCV RNA was
still detectable after 1 month and because
it became undetectable only after 3
months of therapy. A prolonged response
was obtained; a normal ALT level and the
absence of detectable RNA were noted 4
years after the needlestick injury. Anti-
HCV antibodies were detected by ELISA
only at and after month 2. An isolated
reactivity against HCV core protein was
detected by RIBA during month 1, and
the response increased until month 4.
Specific anti–HCV core protein response
rapidly decreased at the end of treatment.
Four years after the needlestick injury oc-
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