3 Discussion
Liver cancer, one of the fatal cancers worldwide, is often treated with
surgery, chemoembolization and chemotherapy1.
Sorafenib and lenvatinib are first-line chemotherapy agents for the
treatment of hepatocellular carcinoma. However, owing to their
unsatisfactory results and numerous adverse side effects, many other
chemotherapeutic drugs have been investigated to treat this
disease2. Apatinib mesylate is a novel tyrosine kinase
inhibitor (TKI) launched and approved in China in 2014. It can
efficiently and competitively bind to vascular endothelial growth factor
receptor-2 (VEGFR2), which inhibits angiogenesis in tumors and inhibits
tumor growth and progression3.
As previously described, VEGFR TKIs have promising therapeutic efficacy
for multiple tumors. However, a few skin toxicities have also been
elucidated in the literature. In 2015, Massey et al. has revealed that
HFS, rash and pruritis were significantly associated with VEGFR TKIs
with the incidence of 0-37%, 13-41% and 14%,
respetively4. Other cutaneous side effects include
alopecia, pigmentation, depigmentation, xeroderma, ulcer and erythema
multiforme have been reported as well4,5. The
management of these lesions could refer to previous
reviews6,7. In terms of apatinib, commonly reported
side effects of apatinib to include hematologic toxicity, proteinuria,
hypertension, fatigue, nausea, vomiting et al.8.
Regarding cutaneous lesions, the hand-foot syndrome (HFS) is the most
common skin reaction, which may result in a 50.5%
incidence5. Moreover, some cases have reported skin
pigmentation, rashes, and BP induced by apatinib9,10.
There was only one case reporting that a 62-year-old female patient
developed drug-induced BP (DIBP) after taking apatinib (0.5 g/d) for two
weeks for breast cancer. In the present case, the patient developed
erythema and multiple bullae on the entire body after 10 days of
apatinib treatment. The Naranjo score (a tool used to assess the
possibility of drug-induced adverse reactions) was 7, which indicated a
probable adverse drug reaction of apatinib mesylate. Combined with skin
biopsy and DIF, apatinib-induced BP was diagnosed. The therapeutic
effect of methylprednisolone was significant. Clinical differential
diagnoses at the time of presentation included paraneoplastic pemphigus
(PNP). PNP is a rare, autoimmune disease associated with neoplasm.
Because the clinical features of PNP are polymorphous, it is sometimes
difficult to distinguish it from other bullous diseases.
Histopathological examination demonstrated suprabasal acantholysis and
dyskeratosis, while DIF demonstrated intercellular IgG and/or C3
deposition in the epidermis, with positive IIF11.
However, the clinical and pathohistological findings of this patient
didn’t conform to PNP, thus, the diagnosis of BP induced by apatinib was
finally made.
In fact, subepithelial autoimmune bullous dermatosis is a disease
spectrum that includes inherited and acquired bullous skin disorders,
such as BP, linear IgA bullous dermatosis, and lichen planus pemphigoid.
They can be induced either spontaneously or by some
drugs12. In our case, BP was indicated by the
disruption of the basal membrane zone (BMZ) through autoantibodies. The
underlying mechanism may be due to drug ingestion acting as an
immunological trigger, which stimulates the hyperproduction of
autoantibodies, and then the autoantibodies appear to target multiple
antigens within BMZ13. Referring to treating
autoimmune bullous dermatoses, the patient has been prescribed
glucocorticoids as initial therapy and achieved satisfactory
result14.