INTRODUCTION
Acanthosis nigricans (AN) is characterized by hyperpigmented,
confluent, velvety papules and plaques in flexural
areas, including the posterior and lateral folds of
the neck, the axillae, the groin, and the umbilicus. It may also be
present over the dorsae of the hands and fingers. Somewhat of
a misnomer, AN is referred to as "malignant" if it is associated
with internal cancers1-3 and, in rare cases, may presage a malignancy.4 Occurring frequently in the setting of hyperinsulinism
and insulin resistance, benign AN is frequently associated
with obesity and endocrinologic abnormalities, such as diabetes
mellitus.5,6 Two previous cases have been reported in which
AN occurred at the site of repeated insulin injections.7,8 In this
article, we describe a third case of insulin injection-induced AN,
document its resolution after discontinuation of injections at
the involved site, and confirm the cause and effect relationship
by demonstrating its recurrence when a noncompliant patient
began injecting the same site yet again.
CASE REPORT
A 63-year-old white male presented with a 6 cm × 6.5 cm asymptomatic,
pigmented, verrucous plaque on his right abdomen at the
site where he had been injecting insulin daily for six months (Figure
1a). He ignored instructions to rotate the injections. A diabetic
exhibiting insulin resistance, the patient required 50 units per mL
of glargine (rDNA origin) (Lantus® SoloSTAR® Pen; sanofi-aventis,
Paris, France) insulin two times per day to control his blood sugar.
Velvety brown plaques typical of AN were also present bilaterally
on the lower neck and in the axillae. Histological assessment of a
6 mm diameter punch biopsy from the abdominal plaque demonstrated
papillomatous projections, mild acanthosis, and marked
hyperkeratosis. In addition, thinning of the epidermis was present
on the sides of papillomatous projections (Figure 2).
A diagnosis of localized drug-induced AN of the abdomen was
made. This occurred in the setting of classic multifocal AN associated
with obesity, diabetes, and hyperinsulinism. The patient
began rotating his insulin injections to other areas on his abdomen
and thighs. Lactic acid 12% lotion was applied daily to
the abdominal AN plaques, with 90% improvement noted after
three months (Figure 1b). At four months, the patient reported
the abdominal area was "nearly normal." On his own, the
patient literally experimented on himself by again repetitively
injecting daily insulin into the original site of the localized AN
"to see what would happen." Within two months, the plaque
had recurred (Figure 1c).
DISCUSSION
While a variety of local cutaneous and subcutaneous adverse
reactions to insulin have been reported, including erythema,
tenderness, wheal and flare, nodule formation, soft swelling,
and lipodystrophy, only two previous cases have documented
AN at the site of repeated injections.7,8 In each case, skin biopsies
were performed, demonstrating mild acanthosis, marked
hyperkeratosis, and papillomatosis. The histopathologic features
of the biopsy from our patient were identical to these
prior cases and typical multifocal AN. In one of the previously
reported cases, AN showed partial resolution after just two
months once injections were rotated to other locations.7 Interestingly,
a number of other drugs have also been implicated in
the induction of AN (Table 1).7-22
The mechanism by which insulin induces AN likely involves
stimulative metabolic and growth-promoting effects at the
insulin receptor.7 The fact that AN can be induced with repeated,
same-site insulin injections, resolves when the injections
