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.