Discussion
Statins are without a doubt a cornerstone of the treatment and
prevention of cardiovascular disease; they are inhibitors of the
conversion of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) into
L-mevalonate, which is the rate-limiting step in cholesterol
biosynthesis, this is achieved by competitive blocking of the active
site of the enzyme HMG-CoA reductase. Therefore, the blockade of the
mevalonate pathway affects cholesterol production and ultimately reduces
serum low-density lipoprotein (LDL) cholesterol levels.
Statins have many other uses thanks to their anti-inflammatory and
immunomodulatory effects, pleiotropic effects ( improvement of
cardiovascular function, anti-fibrotic effects, broad anti-oxidant, and
anti-inflammatory effects, enhancement of bone formation, and neuro- and
renal-protective effects),
(7)
(8)
(9)
(10)
(11)
(12) reasons of which
have been used in autoimmune disorders
(13)
(14), cancer
diseases, (15).
However, statins are not exempt from severe adverse events; cases have
been reported of rhabdomyolysis
(16), lupus-like
syndrome (17),
autoimmune diseases
(18), neuromuscular
diseases, pancreatitis, and hepatitis,
(19); however, even
though the list is vast, the benefits overweight the adverse events
(20)
(21)
Crestor has been associated with skin reactions <0.01%
(20), to our best
knowledge, and after extensive literature review, this is the first case
of leukocytoclastic vasculitis induced by Atorvastatin ANCA negative.
Leukocytoclastic vasculitis is an entity that has been associated with
drugs, infections, cryoglobulinemia, and connective tissue diseases but
can also be idiopathic
(22)
(23).
Symptoms can be organ localized or systemic; systemic involvement varies
from 20 to 50 % and is related to the triggered disease.
(22)
(24)
(25)
(26).
Furthermore, the relapse is associated with the triggered-based disease
in a study with a follow-up of 3 years after the first episode
demonstrated, that the risk factors of chronic disease were
cryoglobulins, arthralgia, and normal temperature at diagnosis
(22) presence of
ANCA-positive, older age, persistent rash, abdominal pain, hematuria,
the severity of the leukocytoclastic, and the absence of IgM deposit on
the vessel walls.
(27); it has been
demonstrated as well by Alalwani et al. that the deposits of IgA are
associated with a worse course of the disease (Gastrointestinal and
renal involvement) and relapse of the same as well.
(22)
(28)
However, LCV associated with drugs is not common
(29)
(22). Even though
some cases of vasculitis have been reported in the literature associated
with statins, only one has been written using atorvastatin, which was
associated with ANCA positives; however, the mechanism of vasculitis
associated with statins (any of them) remains unknown.
Prasad T et al. reported 2 cases, and Haroon et al. reported 1 case of
systemic vasculitis secondary to atorvastatin; all of them were ANCA
positive, with unknown mechanisms; and all the cases presented complete
resolution after stopping atorvastatin and treatment with steroids.
(30)
(31)
(32)
The Food and Drug Administration (FDA) reported 54 cases of
Leukocytoclastic Vasculitis associated with atorvastatin as part of the
surveillance. Still, no proper case was reported, neither clinical
history nor the clinical setting of the presentation.
Our patient did not present any antibody elevations. All the immunologic
panel was negative, which makes a unique case. Based on the timeline of
the clinical history, this LCV was secondary to atorvastatin.
Furthermore, the WHO-UMC Naranjo score was 6 points which makes it
probable, additionally, the patient just started the atorvastatin 2
months before and no other drug was given that could have triggered
leukocytoclastic vasculitis.
The patient had a complete resolution of the vasculitis after stopping
atorvastatin and taking a short course of steroids. The patient has been
following up in our outpatient clinic without any systemic or localized
manifestations of the disease.