Vol. 119 No.

1 January 2015

Adverse drug events in the oral cavity

Anna Yuan, DMD,a,b and Sook-Bin Woo, DMD, MMSca,b

Adverse reactions to medications are common and may have a variety of clinical presentations in the oral cavity.
Targeted therapies and the new biologic agents have revolutionized the treatment of cancers, autoimmune diseases, and
inflammatory and rheumatologic diseases but have also been associated with adverse events in the oral cavity. Some examples
include osteonecrosis, seen with not only bisphosphonates but also antiangiogenic agents, and the distinctive ulcers caused by
mammalian target of rapamycin inhibitors. As newer therapeutic agents are approved, it is likely that more adverse drug events
will be encountered. This review describes the most common clinical presentations of oral mucosal reactions to medications,
namely, xerostomia, lichenoid reactions, ulcers, bullous disorders, pigmentation, fibrovascular hyperplasia, white lesions,
dysesthesia, osteonecrosis, infection, angioedema, and malignancy. Oral health care providers should be familiar with such
events, as they will encounter them in their practice. (Oral Surg Oral Med Oral Pathol Oral Radiol 2015;119:35-47)

A multitude of medications that patients take to control
disease also exposes them to the risk for developing
reactions to the medications. One definition put forward
by Edwards and Aronson in 2000 for “adverse drug
reaction” is “an appreciably harmful or unpleasant re-
action, resulting from an intervention related to the use
of a medicinal product, which predicts hazard from
future administration and warrants prevention or spe-
cific treatment, or alteration of the dosage regimen, or
withdrawal of the product.”1 This definition attempts to
address several important issues related to “appreciable
harm and unpleasantness” and excludes minor re-
actions, addresses the issue of medication error, ad-
dresses injury from nonpharmaceutical agents
(including contaminants and inactive ingredients), and
does not assign disease mechanism. The authors make a
distinction between an adverse effect (adverse outcome
attributed to an action of the drug) and an adverse event
(adverse outcome that occurs when a patient is on the
drug but that may not be caused by the drug).1
The term used currently that satisfies both regulatory
bodies as well as patient safety advocates is “adverse
drug event” which includes (1) harm caused by a drug
(commonly known as adverse drug reaction), (2) harm
caused by appropriate drug use (usually referred to as a
side effect), and (3) medication errors.2 This review will
focus on common adverse drug events (ADEs), as
defined by Nebeker et al.2 from a clinical perspective.
Most fall under the category of side effects, although
whether the patients were significantly harmed by the
event is probably subject to interpretation. Although the
term “medication” is preferred over “drug,” we are
using the term ADE because it is the convention.
Diagnosis is based on history and chronology of the
adverse oral reaction. Typically, these changes are
detected within weeks or months after taking the
medications. Some lesions, such as lichenoid drug
reactions, may present asymptomatically initially but
become symptomatic years later, making the rela-
tionship between start of drug use and development of
ADE difficult to ascertain. The presence of the oral
condition predating the administration of the medi-
cation must be excluded, and this may be difficult to
determine if the patient has not seen a health care
provider in a long time. Resolution should occur after
discontinuation of the suspected medication, although
this may necessitate the use of topical corticosteroids
for inflammatory conditions. Recurrence with
rechallenge confirms the diagnosis, although this may
not be feasible if the ADEs are unpleasant, severe, or
life-threatening. Concurrent medications must be
noted.
The benefits of using any particular medication must,
of course, always be weighed against the side effects,
and some considerations include the necessity for the
medication and availability of substitute agents, how
severe the side effects are (e.g., asymptomatic oral
pigmentation vs highly morbid necrolytic syndromes),

Portions of this were presented at the Jonathan A. Ship Lecture at the

annual meeting of the American Academy of Oral Medicine in 2013
in San Antonio, Texas.
a
Statement of Clinical Relevance
Division of Oral Medicine, Brigham & Women’s Hospital, Boston,
Massachusetts. Adverse drug events in the oral cavity are common
b
Department of Oral Medicine, Infection and Immunity, Harvard
and will likely increase as newer therapeutic agents
School of Dental Medicine, Boston, Massachusetts.
Received for publication Jun 4, 2014; returned for revision Aug 18, are approved. Health care providers should famil-
2014; accepted for publication Sep 10, 2014. iarize themselves with such events. This review de-
Ó 2015 Elsevier Inc. Open access under CC BY-NC-ND license. scribes common and uncommon oral mucosal
2212-4403 reactions to medications.
http://dx.doi.org/10.1016/j.oooo.2014.09.009

35

Descargado para Anonymous User (n/a) en ClinicalKey Espanol Colombia, Ecuador & Peru Flood Relief de ClinicalKey.es por Elsevier en abril 27, 2017.
Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2017. Elsevier Inc. Todos los derechos reservados.
ORAL MEDICINE
36 Yuan and Woo
Table I. Drug-induced oral reactions
Hyposalivation/xerostomia
Lichenoid reaction/lichen planus
Aphthous-like ulcers
Bullous disorders
Pigmentation
Fibrovascular hyperplasia
Keratosis/epithelial hyperplasia
Dysesthesia
Osteonecrosis of the jaws
Infection
Angioedema
Malignancy
the frequency of occurrence of such ADEs, whether the
ADE can be eliminated by lowering the dose, and
whether the ADE may be easily treated.1,2
Drug-induced cutaneous reactions are common and
varied in presentation, but only a limited number of
reaction patterns occur in the oral cavity. This is likely
due to the higher turnover rate in the oral mucosa
compared with that on the skin, and this does not allow
easy detection of the spectrum of subtle clinical
changes on the skin. The oral lesions to be discussed
fall into several categories (Table I).
HYPOSALIVATION/XEROSTOMIA
Medication use is one of the most common causes of
both xerostomia and hyposalivation. Many middle-aged
and older patients in the United States are on multiple
medications (“polypharmacy”), and even medications
with small anticholinergic effects may act synergisti-
cally in combination to cause oral symptoms of dryness
and discomfort (Figure 1). Dry mouth is listed as an
adverse effect for over 500 medications.3 In a system-
atic review, xerostomia was reported to be one of the
most common oral adverse effects associated with over
80% of the 100 most prescribed medications in the
United States.4 The most frequently reported medica-
tion classes that result in hyposalivation are antide-
pressants, antipsychotics, antihistamines, muscarinic
receptor and a-receptor antagonists, antihypertensives
(e.g., diuretics, b-blockers, and angiotensin-converting
enzyme [ACE] inhibitors), bronchodilators, and skeletal
muscle relaxants.3,5 Other culprits include chemo-
therapy agents, appetite suppressants, decongestants,
antimigraine drugs, opioids, benzodiazepines, hyp-
notics, histamine 2 (H2) receptor antagonists and proton
pump inhibitors, systemic retinoids, antiehuman im-
munodeficiency virus medications, and cytokine
therapy.3,5
A study of 601 patients reported that older in-
dividuals were almost three times more likely to report
xerostomia, and patients taking one or more drugs were
Descargado para Anonymous User (n/a) en ClinicalKey Espanol Colombia, Ecuador & Peru Flood Relief de ClinicalKey.es por Elsevier en abril 27, 2017.
Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2017. Elsevier Inc. Todos los derechos reservados.
OOOO
January 2015
Fig. 1. Hyposalivation from polypharmacy.
more than twice as likely to do so compared with
medication-free patients; this prevalence increased with
increasing number of medications used (16.7% of pa-
tients reported xerostomia with one medication daily vs
33.3% with two to three medications daily vs 36.9% at
greater than three medications daily).6 Persistent
hyposalivation can lead to infections, such as candidi-
asis and dental caries, as well as bacterial sialadenitis.7
The loss of lubrication also results in erythema and
susceptibility of the mucosa to frictional trauma against
teeth; discomfort and burning may be profound.
LICHENOID REACTION/LICHEN PLANUS
One of the most common inflammatory conditions
affecting the skin and oral mucosa is lichen planus (LP).
LP is an immune-mediated process, where T cells
mediate the destruction of the basal cells of the
epithelium.8 Oral LP presents as white striations or
papules often associated with erythema or erosion and
ulcers, most commonly in a bilaterally symmetric
manner, often on the buccal mucosa, tongue, and
gingiva.9 Many medications are known to cause cuta-
neous lichenoid hypersensitivity reactions (LHRs),
which are often difficult to distinguish clinically and
histopathologically from idiopathic cutaneous LP.10,11
Cutaneous LHRs present as skin eruptions character-
ized by purplish, pruritic keratotic papules and plaques,
usually without the classic Wickham striae, on the trunk
and extremities instead of the flexural regions.11-13 It
has been postulated that active thiol groups found in the
chemical structure of such medications as piroxicam,
sulfasalazine, and glipizide play a role in inciting such
reactions.14,15 It is, therefore, likely that these same
OOOO
Volume 119, Number 1
Fig. 2. Lichenoid tissue reaction from rituximab.
medications may cause an oral LHR and that it can
resemble idiopathic oral LP (Figure 2).
The two classes of medications historically associ-
ated with oral LHRs are nonsteroidal anti-inflammatory
drugs (NSAIDs) and antihypertensive agents, including
b-blockers, ACE inhibitors, and diuretics (in particular
hydrochlorothiazide).7,16,17 Sulfonylurea antidiabetic
medications (e.g., tolbutamide and glipizide), antifun-
gals (e.g., ketoconazole), anticonvulsants (e.g., carba-
mazepine), immunomodulatory drugs (e.g., gold salts
and penicillamine), sulfasalazine, allopurinol, and
lithium have been reported to elicit oral LHRs.18,19 Of
historical interest, Grinspan syndrome was introduced
at the 1963 Congress of Dermatology as a clinical
presentation of a triad of oral LP, diabetes mellitus, and
hypertension; it is now generally accepted that drug
therapy for hypertension in particular and likely dia-
betes mellitus is capable of provoking oral
LHRs.11,20,21
One theory regarding the pathogenesis of LHRs is
that susceptible patients have polymorphisms of the
cytochrome P450 enzymes (CYPs), which results in
poor or intermediate CYP metabolism of some medi-
cations. One group of investigators reported higher
CYP2-D6 among females (P > .05) and higher CYP2-
D6*4 among patients with oral LP (50%) versus those
in the general population (30%), although this is of
questionable clinical significance.22,23
It is often difficult to reach a consensus on diagnostic
criteria, in part due to the fact that LHRs, once well-
established, may persist after cessation of the drug
unless rigorously treated. However, McCartan et al.
suggested that a history of the current use of an LHR-
inducing medication in combination with consistent
histopathology is likely sufficient, although the authors
also suggested that testing for the presence of circu-
lating basal cell cytoplasmic autoantibodies may be
helpful.24,25
LP has been associated with thyroid disease in
several studies. Siponen et al. reported that 15% and
Descargado para Anonymous User (n/a) en ClinicalKey Espanol Colombia, Ecuador & Peru Flood Relief de ClinicalKey.es por Elsevier en abril 27, 2017.
Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2017. Elsevier Inc. Todos los derechos reservados.
REVIEW ARTICLE
Yuan and Woo 37
13% of patients with oral LP and oral lichenoid lesions,
respectively, had thyroid disease compared with 8% of
controls.26 This raises the question of whether the le-
sions result from the disease or from the medications
used to treat the disease. A subsequent study found that
patients with oral LP were 3.4 times more likely to be
taking levothyroxine than not (P ¼ .001).27 Lo Muzio
et al. noted that oral LP occurred in 14.3% of patients
with Hashimoto thyroiditis versus 1% of the general
population.28
Several other classes of medications are also asso-
ciated with the development of cutaneous LP or LHRs.
3-hydroxy-3-methylglutaryl-coenzyme A inhibitors,
such as pravastatin, simvastatin, fluvastatin, and lova-
statin, have been implicated in causing cutaneous LHRs
with mucosal involvement.29-31 The tyrosine kinase
inhibitor imatinib has been implicated in LHRs,
particularly in the oral cavity.32-36 In a study of the
aromatase inhibitor letrozole used for breast cancer,
32.4% of patients were noted to have an adverse cuta-
neous reaction, and another group reported that 16
patients (0.9%) developed lichenoid keratosis over an
8-year study period.37,38 Antituberculosis drugs, such
as ethambutol, pyrazinamide, isoniazid, and rifampicin,
also have been reported to cause cutaneous LHRs.39-41
A recent case report noted an association between
antituberculosis medications and hyperpigmented
macules and lichenoid papules in the oral cavity; these
lesions were bilateral and symmetric, but classic LP
reticulations were absent.42
Biologic agents are being used with increasing fre-
quency for the management of rheumatoid arthritis,
ankylosing spondylitis, and psoriatic arthritis and in
oncology, and reports of LHRs have begun to appear in
the literature. The novel anti-CD20 monoclonal anti-
body obinutuzumab was reported to cause LHRs on the
skin and oral ulcers.43 Asarch et al. reported two cases
of oral LP (more accurately, LHRs) in patients taking
tumor necrosis factor alpha (TNF-a) inhibitors inflix-
imab and adalimumab and 12 cases involving the TNF
receptor fusion proteins etanercept and abatacept.44
Infliximab and certolizumab used to treat Crohn disease
have both been linked to biopsy-proven oral LP.45,46
This seems paradoxical, since oral LP is mediated by
TNF-a. However, it has been suggested that there may
be upregulation of interferon alpha when TNF-alpha is
inhibited.44 Interferon alpha then activates T cells and
dendritic cells, causing an inflammatory response.44,47
Fixed drug eruptions (FDEs) in the oral cavity are
lesions that recur at the same site each time the
offending medication is taken.48 Oral mucosal lesions
are infrequently reported and can be accompanied by
skin or genital involvement.49,50 The presentation can
range from bullous to erosive, hyperpigmented, pruitic,
or erythematous lesions.49 A number of first- and
ORAL MEDICINE OOOO
38 Yuan and Woo January 2015

Fig. 3. Sirolimus-induced aphthous-like ulcers. Fig. 4. Methotrexate-induced oral ulcer.

second-generation antihistamines have been known to

cause FDEs on the skin.51,52 The third-generation
antihistamine levocetirizine was reported in a case of
FDE involving the oral (lower lip and tongue) and
genital tissues (glans penis).53 Use of acetaminophen
was reported to result in erythematous and papular
FDEs on the hard palate and skin; naproxen and oxi-
cams have caused lesions on the lips48,54; and flucon-
azole has caused lesions of the palatal mucosa and oral
bullae.55,56 Co-trimoxazole, oxyphenbutazone, tetracy-
cline, clarithromycin, and gabapentin have also been
implicated in the occurrence of oral FDEs.50,57,58

Fig. 5. Ulcerative mucositis secondary to chemotherapy.

APHTHOUS-LIKE AND NONeAPHTHOUS-
LIKE ULCERS
Conventional chemotherapy agents, such as 5-fluo-
Idiopathic aphthous ulcers usually begin in the first two
rouracil, cisplatin, methotrexate, and hydroxyurea, are
decades of life and appear as ovoid to round ulcers
stomatotoxic and cause oral ulcers and ulcerative
usually 1 cm or less with a yellowish fibrinous mem-
mucositis (Figure 4).69-71 These ulcers tend to be larger
brane and surrounding erythema involving the non-
and more diffuse and do not have the ovoid, well-
keratinized mucosa.5 “Aphthous-like” or aphtheiform
demarcated appearance of aphthous ulcers (Figure 5).
ulcers is the term used for oral ulcers where there is a
Mycophenolate mofetil has been reported to cause
known etiology, as these resolve when the underlying
ulcers on the tongue, palate, labial mucosa, and gingiva
etiology is effectively managed.
in recipients of solid organ transplants, but these ulcers
NSAIDs were one of the earliest classes of drugs
resolve on cessation of medication, as in the case of
associated with the development of aphthous-like ulcers
tacrolimus.72-77 Rare cases of ulcers associated with
in the oral cavity.59-61 Piroxicam, in particular, was
multitargeted kinase inhibitors (MTKIs) have been
shown to cause such ulcers, possibly because it contains
reported.78
a thiol group.5,60,62,63 Naproxen, trimethoprim-sulfa-
methoxazole, cyclooxygenase-2 inhibitors (e.g., refe-
coxib), and the angiotensin receptor blocker losartan BULLOUS DISORDERS
have been implicated in the development of aphthous- Medication-induced autoimmune bullous disorders of
like ulcers.49,64,65 the skin are not uncommon, whereas such disorders
More recently, aphthous-like ulcers have been presenting in the oral cavity are rare. The development
documented in patients with metastatic tumors treated of simultaneous oral and cutaneous pemphigus vulgaris
with mammalian target of rapamycin inhibitors, has been noted with the use of thiol radicalecontaining
including sirolimus, temsirolimus, everolimus, and drugs,64,79,80 such as penicillamine81,82 and NSAIDs
ridaforolimus (Figure 3).66-68 However, unlike idio- (see Figure 4).83 Cutaneous bullous pemphigoid has
pathic recurrent aphthous ulcers, on withdrawal of been associated with antipsychotic medications,
therapy, these regress completely without recurrence. spironolactones, and sulfonamides.80,84-86 Lupus

Descargado para Anonymous User (n/a) en ClinicalKey Espanol Colombia, Ecuador & Peru Flood Relief de ClinicalKey.es por Elsevier en abril 27, 2017.
Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2017. Elsevier Inc. Todos los derechos reservados.
OOOO
Volume 119, Number 1
Fig. 6. Palatal mucosal pigmentation associated with
imatinib.
erythematosus of the skin has been observed in patients
using procainamide, hydralazine, and biologic agents,
such as anti-TNF inhibitors.87-89
Erythema multiforme (EM), major or minor, can
affect both the skin and mucous membranes. It presents
as irregular oral ulcers with diffuse erythema and target
lesions of the skin. It is a hypersensitivity reaction, most
commonly to an infectious agent, such as herpes sim-
plex virus and less commonly to Mycoplasma pneu-
monia in children; approximately 18% of cases
represent hypersensitivity reactions to medications.90-92
EM of the skin and oral mucous membranes has been
reported with the administration of infliximab and
adalimumab.93,94
Steven Johnson syndrome (SJS) and toxic
epidermal necrolysis (TEN) are severe necrolytic hy-
persensitivity reactions, which, unlike EM, are much
more commonly associated with the use of medica-
tions and may be life-threatening.92 SJS and TEN
almost always involve the mucous membranes of the
mouth, eye, and genitalia, sometimes extensively.
Antimicrobials (amoxicillin/clavulanic acid)95 and
anticonvulsants (phenytoin and lamotrigine) have been
implicated.96,97 In the Han Chinese populations, SJS
and TEN caused by anticonvulsants, such as pheno-
barbital, phenytoin, and carbamazepine, are associated
with HLA-B*1502 (odds ratio [OR] 1357), whereas
reactions to allopurinol are associated with HLA-
B*5801 (OR 580).98-100 In the Thai population, car-
bamazepine is also associated with SJS and TEN in a
large number of patients (OR 75).99 In Europeans, SJS
and TEN caused by sulfamethoxasole has been asso-
ciated with HLA-B*38, NSAIDs with HLA-B*73,101
and HIV-1 reverse-transcriptase inhibitor abacavir
with HLA-B*5701.102 Other drugs implicated include
lamotrigine, phenytoin, phenobarbital, lenalido-
mide103; co-trimoxazole, sulfonamides, sulfasalazine,
and oxicam104,105; nivirapine106; transexamic acid107;
and rituximab.108
Descargado para Anonymous User (n/a) en ClinicalKey Espanol Colombia, Ecuador & Peru Flood Relief de ClinicalKey.es por Elsevier en abril 27, 2017.
Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2017. Elsevier Inc. Todos los derechos reservados.
REVIEW ARTICLE
Yuan and Woo 39
PIGMENTATION
Metabolites of such medications as the tetracyclines,
minocyclines, antimalarial drugs (e.g., hydroxy-
chloroquine, mepacrine, and quinacine), and phenazine
dyes (e.g., clofazimine) may be deposited in the oral
mucosa. Such drug metabolites chelate with iron and
melanin, which results in pigmentation of the hard
palatal mucosa, and have a specific histopathology
(Figure 6).109-113 Tetracycline and minocycline are also
deposited in teeth, bones, thyroid, and sclera and cause
mucosal and nail pigmentation.114,115 The tyrosine ki-
nase inhibitor imatinib, used to treat chronic myeloge-
nous leukemia and acute lymphoblastic leukemia, can
cause hyper- or hypopigmentation of the skin, hyper-
pigmentation of nails, and diffuse blue-gray pigmenta-
tion on the palatal mucosa, with similar characteristic
histopathology.116,117 It is unclear whether second-
generation tyrosine kinase inhibitors such as dasatinib,
nilotinib, and bosutinib will have the same effect.
Other medications that have been noted to cause oral
mucosal pigmentation are zidovudine (on the
tongue)118,119; oral contraceptives (on the maxillary and
mandibular gingiva)120; and chemotherapy agents, such
as such as doxorubicin, docetaxel, and cyclophospha-
mide (on the tongue dorsum, buccal mucosa, and
nails).121-123 Pigmentation of the facial skin has been
noted with the use of amiodorone and phenothiazines
(chlorpromazine).124,125 Stimulation of melanocytes
without metabolite deposition is postulated to be the
mechanism, and, interestingly, pigmentation does not
occur on the palatal mucosa.
FIBROVASCULAR HYPERPLASIA
Calcium channel blockers, in particular, nifedipine and
amlodipine, are antihypertensive agents that induce
hyperplasia of the gingival tissues.126,127 This presents
as a diffuse, generalized, often nodular overgrowth of
densely fibrous gingival tissue. The resulting gingival
enlargement is exacerbated by plaque-induced inflam-
mation, and there may be a genetic predisposition.128 It
has been suggested that the mechanism is due to
decreased cellular folic acid uptake leading to decreased
activity of matrix metalloproteinases and the failure to
activate collagenase.129-131
Calcineurin inhibitors, such as cyclosporine or, less
frequently, tacrolimus, also induce inflammatory fibro-
vascular hyperplasias in the oral cavity. However, these
present as localized polypoid fibrous tumors and are
more often seen on the tongue and buccal mucosa rather
than on the gingiva (Figure 7).132,133 The increased
production of collagen is thought to be due to both the
reduced activity of matrix metalloproteinases and the
increased activity of tissue inhibitors of metal-
loproteinases.134-136 It has also been proposed that
ORAL MEDICINE
40 Yuan and Woo
Fig. 7. Fibrovascular hyperplasia with ulceration associated
with tacrolimus.
phenytoin and cyclosporine cause an increase in the
expression of interleukins (IL-1, IL-6), which may
induce oral mucosal mesenchymal stem cells to
differentiate toward a pro-fibrotic phenotype.137-139
KERATOSIS/EPITHELIAL HYPERPLASIA
Palifermin is a recombinant keratinocyte growth factor
delivered intravenously to reduce the incidence and
severity of mucositis related to autologous hematopoi-
etic stem cell transplantation, chemotherapy, and
radiotherapy.140,141 It has been associated with mouth
or tongue thickness and white discoloration in 17% of
patients.142 The diffuse, thickened white plaques
observed in the mouth as a response to palifermin are
likely due to increased thickness of the oral epithelium
and/or keratin layer as a result of the proliferation of
epithelial cells.143
DYSESTHESIAS
Oral dysesthesias, such as sensitivity, burning, dysgeu-
sia, and other altered sensations without clinical signs,
may be caused by medications. It must be noted that
dysgeusia can be secondary to hyposalivation instead of
being the direct effect of a drug.144 Damage to the sali-
vary glands reduces the production of saliva, the solution
in which chemoreceptors in the taste buds of the tongue
bind their receptor molecules.145 A study on dysgeusia
and dysosmia was reported for several drug classes,
including macrolides, such as clarithromycin (17%);
antimycotics, such as terbinafine (9%); and fluo-
roquinolones (8%), as well as protein kinase inhibitors,
ACE-inhibitors, statins, and proton pump inhibitors (3%-
5% each).146 The mechanism is multifactorial and may
be a combination of drugereceptor inhibition, alteration
of neurotransmitter function, disturbance of action po-
tentials in neurons, and dysfunctional sensory modula-
tion in the brain.146,147 Vismodegib, a first-in-class,
small-molecule inhibitor of the hedgehog pathway
Descargado para Anonymous User (n/a) en ClinicalKey Espanol Colombia, Ecuador & Peru Flood Relief de ClinicalKey.es por Elsevier en abril 27, 2017.
Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2017. Elsevier Inc. Todos los derechos reservados.
OOOO
January 2015
produced dysgeusia in 51% of participants in a phase 1
trial for management of advanced basal cell
carcinomas.148
Neurologic complications of chemotherapy are well
described in the literature. The pathobiology of pe-
ripheral neuropathy is complex and could be attributed
to neuronopathy, axonopathy, myelinopathy, and
intraepidermal nerve fiber degeneration.149 Chemo-
therapy-associated peripheral neuropathies are often
associated with the use of taxanes,150 platinum com-
pounds, thalidomide, bortezomib,151 and vinca alka-
loids, such as vincristine and vinblastine.152-155
MTKIs (e.g., sunitinib and sorafenib) downregulate a
variety of receptors, including vascular endothelial
growth factor (VEGF), platelet-derived growth factor,
fibroblast growth factor, c-kit, FMS-like tyrosine kinase
3 (FLT-3), BRAF, and RET. The development of oral
dysesthesias is significantly associated with the devel-
opment and severity of palmareplantar eryth-
rodysesthesia in patients on MTKIs.156,157 A study of
over 200 patients reported “stomatitis” symptoms in
26% of patients on sorafenib and in 36% of patients on
sunitinib in the absence of oral findings.157 Koll-
mannsberger et al. reported oral toxicities in up to 60%
of patients and noted that the type of “stomatitis”
observed was characterized by oral mucosal sensitivity,
taste changes, and xerostomia without noticeable
physical changes.158 They may fall within the spectrum
of burning mouth syndrome or oral dysesthesia
disorders.
OSTEONECROSIS OF THE JAWS
Bisphosphonates and denosumab (monoclonal antibody
against receptor activator of nuclear factor kappa-B
ligand) are antiresorptive medications that markedly
slow bone turnover and remodeling and therefore in-
crease bone density; they are used to treat post-
menopausal osteoporosis and reduce skeletal-related
events during cancer therapy (e.g., for plasma cell
myeloma and metastatic cancers).159-161 Osteonecrosis
is an ADE presenting as either exposed bone or a
nonhealing extraction socket (Figure 8).162-164 A stage
0 variant exists where bone is not exposed.159,165,166
Bisphosphonates also exhibit antiangiogenic activ-
ity.167 Antiangiogenic agents, such as bevacizumab and
sunitinib, which act against VEGF, either used alone or in
combination with bisphosphonates, also lead to the
development of osteonecrosis in some patients.168-173 In
fact, higher incidences of osteonecrosis have been seen
with combination of such anti-VEGF therapies and
bisphosphonates than with bisphosphonates alone.174-177
It is unclear whether mammalian target of rapamycin
inhibitors alone may cause osteonecrosis, since it has
been recently reported that patients who developed this
condition had also been on intravenous bisphosphonates
OOOO
Volume 119, Number 1
Fig. 8. Osteonecrosis of the jaw associated with denosumab.
for years.177-179 The term “medication-induced osteo-
necrosis” may be a more appropriate general term for
such osteonecrotic lesions, since medications other than
antiresorptive agents may be involved.
INFECTION
Patients on long-term immunosuppressive therapy may
develop a variety of opportunistic infections in the oral
cavity (Figure 9). It is well established that immuno-
suppressed patients frequently develop pseudomem-
branous candidiasis,180 fungal infections,181-183 and
viral infections.184-188 TNF-a therapy specifically has
been linked to an increased risk of serious infections,
such as tuberculosis and meningitis, especially when
combined with other immunomodulatory agents.189,190
Patients receiving infliximab and adalimumab have
been shown to be at an increased risk for tuberculosis
(OR 2.0) as well as histoplasmosis and coccidiomy-
cosis.191 Disease-modifying antirheumatic drugs, such
as methotrexate, abatacept, and alefacept, have been
associated with herpes simplex or herpes zoster infec-
tion, deep fungal infections, and tuberculosis.192
ANGIOEDEMA
Medication-induced angioedema has been observed
with the use of multiple agents, most commonly ACE
inhibitors.193,194 This abrupt-onset swelling of the
orofacial region and lips can compromise the airway
and be life-threatening. Angioedema is mediated by
inflammatory cytokines, complement activation, and
vascular permeability. It has also been reported with the
use of other antihypertensive agents, such as angio-
tensin receptor blockers,195 calcium channel
blockers,196 and hydrochlorothiazide,197 as well as an-
tiplatelet agents, such as thienopyridine and clopidog-
rel.198 The use of the statin class of medications,
including simvastatin, fluvastatin, atorvastatin, and
pravastatin, is infrequently associated with this side
effect.199-202
Descargado para Anonymous User (n/a) en ClinicalKey Espanol Colombia, Ecuador & Peru Flood Relief de ClinicalKey.es por Elsevier en abril 27, 2017.
Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2017. Elsevier Inc. Todos los derechos reservados.
REVIEW ARTICLE
Yuan and Woo 41
Fig. 9. Candidiasis from topical steroid therapy.
MALIGNANCY
A number of chemotherapy and immunomodulating
agents have been shown to increase the risk of lympho-
proliferative disorders and neoplasms.203 Patients taking
methotrexate for rheumatoid arthritis sometimes develop
lymphoproliferative diseases; in 23% of cases, the disease
regressed after discontinuation of the medication204-206;
these diseases are often associated with Epstein-Barr virus
infection and occur infrequently.205,207,208
Topical tacrolimus applied on the skin in the murine
model exhibited development of squamous cell carci-
nomas in 8.5% of cases and benign papillomas 91.5%
of cases.209 There have been anecdotal reports of
squamous cell carcinoma developing in patients with
oral LP treated with tacrolimus ointment.210,211 Tacro-
limus has been shown to have an effect on both the
MAPK and the p53 pathways, which are important in
cancer signaling.211 In a long-term study of recipients
of liver transplants, 45% of de novo malignancies were
on the skin, with tacrolimus immunosuppression cited
as a risk factor (hazard ratio 2.06).212 There have been
only sporadic case reports of squamous cell carcinomas
of the skin and cutaneous T-cell lymphomas occurring
after tacrolimus and pimecrolimus application.213-216
It has also been reported that 9.6% of patients on
combinations of immunomodulating agents, such as
azathioprine, cyclophosphamide, cyclosporine, or
mycophenolate mofetil, for pemphigus or pemphigoid
may develop a secondary malignancy.217
Malignancies induced by biologic agents have been
reported in the literature. Bongartz et al. analyzed nine
randomized, controlled trials of infliximab and adali-
mumab used in 3493 patients and found a three-fold
increase of malignancy (OR 3.3).191 The secondary
cancers were significantly more common in patients
treated with higher doses of anti-TNF antibodies and
primarily consisted of basal cell carcinomas and lym-
phomas.191 However, another study evaluated 18 clin-
ical trials using TNF-a inhibitors and found no increase
in malignancy or infection.218
ORAL MEDICINE
42 Yuan and Woo
The issue of drug-induced malignancy is still
controversial, and it is difficult to remove confounding
factors from studies that show an association. Some
conditions themselves predispose the patient to devel-
oping malignancy regardless of the therapy received
(e.g., severe rheumatoid arthritis and the development
of lymphoma219) and the use of powerful immuno-
suppressive medications likely increase the risk.
Furthermore, the patient may have received many years
of other immunosuppressive therapies that predisposed
them to malignancy.210,220 In cases of oral LP, for
example, that are resistant to topical steroid therapy, the
clinician should carefully weigh the benefit of using
topical tacrolimus against the rare anecdotal cases of
squamous cell carcinoma that developed as a result of
its use.
CONCLUSION
Adverse drug events in the oral cavity are common and
may have a variety of clinical presentations. With new
therapeutic agents being introduced into clinical prac-
tice, it is likely that more ADEs will be encountered.
The advent of targeted therapies in oncology has pro-
duced a number of novel complications in the oral
cavity. Oral health care providers should be aware of
the manifestations of ADEs encountered in their
practice.
The authors would like to thank Dr Jennifer Frustino for her
assistance with this manuscript.
REFERENCES
1. Edwards IR, Aronson JK. Adverse drug reactions: definitions,
diagnosis, and management. Lancet. 2000;356:1255-1259.
2. Nebeker JR, Barach P, Samore MH. Clarifying adverse drug
events: a clinician’s guide to terminology, documentation, and
reporting. Ann Intern Med. 2004;140:795-801.
3. Femiano F, Rullo R, di Spirito F, Lanza A, Festa VM, Cirillo N.
A comparison of salivary substitutes versus a natural sialogogue
(citric acid) in patients complaining of dry mouth as an adverse
drug reaction: a clinical, randomized controlled study. Oral Surg
Oral Med Oral Pathol Oral Radiol Endod. 2011;112:e15-e20.
4. Zavras AI, Rosenberg GE, Danielson JD, Cartsos VM. Adverse
drug and device reactions in the oral cavity: surveillance and
reporting. J Am Dent Assoc. 2013;144:1014-1021.
5. Scully C, Bagan JV. Adverse drug reactions in the orofacial
region. Crit Rev Oral Biol Med. 2004;15:221-239.
6. Villa A, Abati S. Risk factors and symptoms associated with
xerostomia: a cross-sectional study. Aust Dent J. 2011;56:
290-295.
7. Korstanje MJ. Drug-induced mouth disorders. Clin Exp Der-
matol. 1995;20:10-18.
8. Lavanya N, Jayanthi P, Rao UK, Ranganathan K. Oral lichen
planus: an update on pathogenesis and treatment. J Oral Max-
illofac Pathol. 2011;15:127-132.
9. Piboonniyom SO, Treister N, Pitiphat W, Woo SB. Scoring
system for monitoring oral lichenoid lesions: a preliminary
Descargado para Anonymous User (n/a) en ClinicalKey Espanol Colombia, Ecuador & Peru Flood Relief de ClinicalKey.es por Elsevier en abril 27, 2017.
Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2017. Elsevier Inc. Todos los derechos reservados.
OOOO
January 2015
study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod.
2005;99:696-703.
10. Van den Haute V, Antoine JL, Lachapelle JM. Histopathological
discriminant criteria between lichenoid drug eruption and idio-
pathic lichen planus: retrospective study on selected samples.
Dermatologica. 1989;179:10-13.
11. Lowell Goldsmith SK, Gilchrest Barbara, Paller Amy,
Leffell David, Wolff Klaus, eds. Fitzpatrick’s Dermatology in
General Medicine. 8th ed. Boston, MA: McGraw-Hill Profes-
sional; 2012.
12. Fessa C, Lim P, Kossard S, Richards S, Penas PF. Lichen pla-
nus-like drug eruptions due to beta-blockers: a case report and
literature review. Am J Clin Dermatol. 2012;13:417-421.
13. Halevy S, Shai A. Lichenoid drug eruptions. J Am Acad Der-
matol. 1993;29:249-255.
14. Reinhardt LA, Wilkin JK, Kirkendall WM. Lichenoid eruption
produced by captopril. Cutis. 1983;31:98-99.
15. Breathnach SM. Mechanisms of drug eruptions: Part I. Australas
J Dermatol. 1995;36:121-127.
16. Sugerman PB, Savage NW, Zhou X, Walsh LJ, Bigby M. Oral
lichen planus. Clin Dermatol. 2000;18:533-539.
17. Baricevic M, Mravak Stipetic M, Situm M, et al. Oral bullous
eruption after taking lisinoprildcase report and literature re-
view. Cent Eur J Med. 2013;125:408-411.
18. Schlosser BJ. Lichen planus and lichenoid reactions of the oral
mucosa. Dermatol Ther. 2010;23:251-267.
19. Artico G, Bruno IS, Seo J, Hirota SK, Acay R, Migliari DA.
Lichenoid reaction to carbamazepine in the oral mucosa: case
report. An Bras Dermatol. 2011;86:S152-S155.
20. Grinspan D, Diaz J, Villapol LO, et al. [Lichen ruber planus of
the buccal mucosa. Its association with diabetes]. Bull Soc Fr
Dermatol Syphiligr. 1966;73:898-899.
21. Aljabre SH. Grinspan’s syndrome. J Am Acad Dermatol.
1994;30:671.
22. Kragelund C, Hansen C, Reibel J, et al. Polymorphic drug
metabolizing CYP-enzymesea pathogenic factor in oral lichen
planus? J Oral Pathol Med. 2009;38:63-71.
23. Kragelund C, Hansen C, Reibel J, et al. Can the genotype or
phenotype of two polymorphic drug metabolising cytochrome
P450-enzymes identify oral lichenoid drug eruptions? J Oral
Pathol Med. 2010;39:497-505.
24. McCartan BE, McCreary CE. Oral lichenoid drug eruptions.
Oral Dis. 1997;3:58-63.
25. Thornhill MH, Sankar V, Xu XJ, et al. The role of histopatho-
logical characteristics in distinguishing amalgam-associated oral
lichenoid reactions and oral lichen planus. J Oral Pathol Med.
2006;35:233-240.
26. Siponen M, Huuskonen L, Laara E, Salo T. Association of oral
lichen planus with thyroid disease in a Finnish population: a
retrospective case-control study. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod. 2010;110:319-324.
27. Robledo-Sierra J, Mattsson U, Jontell M. Use of systemic
medication in patients with oral lichen planusda possible as-
sociation with hypothyroidism. Oral Dis. 2012;19:313-319.
28. Lo Muzio L, Santarelli A, Campisi G, Lacaita M, Favia G. Possible
link between Hashimoto’s thyroiditis and oral lichen planus: a novel
association found. Clin Oral Investig. 2013;17:333-336.
29. Pua VS, Scolyer RA, Barnetson RS. Pravastatin-induced
lichenoid drug eruption. Australas J Dermatol. 2006;47:57-59.
30. Roger D, Rolle F, Labrousse F, Brosset A, Bonnetblanc JM.
Simvastatin-induced lichenoid drug eruption. Clin Exp Derma-
tol. 1994;19:88-89.
31. Sebok B, Toth M, Anga B, Harangi F, Schneider I. Lichenoid
drug eruption with HMG-CoA reductase inhibitors (fluvastatin
and lovastatin). Acta Derm Venereol. 2004;84:229-230.
OOOO
Volume 119, Number 1
32. Gomez Fernandez C, Sendagorta Cudos E, Casado Verrier B,
Feito Rodriguez M, Suarez Aguado J, Vidaurrazaga Diaz de
Arcaya C. Oral lichenoid eruption associated with imatinib
treatment. Eur J Dermatol. 2010;20:127-128.
33. Pascual JC, Matarredona J, Miralles J, Conesa V, Borras-Blasco J.
Oral and cutaneous lichenoid reaction secondary to imatinib:
report of two cases. Int J Dermatol. 2006;45:1471-1473.
34. Lim DS, Muir J. Oral lichenoid reaction to imatinib (STI 571,
Gleevec). Dermatology. 2002;205:169-171.
35. Wahiduzzaman M, Pubalan M. Oral and cutaneous lichenoid
reaction with nail changes secondary to imatinib: report of a case
and literature review. Dermatol Online J. 2008;14:14.
36. Ena P, Chiarolini F, Siddi GM, Cossu A. Oral lichenoid eruption
secondary to imatinib (Glivec). J Dermatolog Treat. 2004;15:
253-255.
37. Mann BS, Johnson JR, Kelly R, Sridhara R, Williams G,
Pazdur R. Letrozole in the extended adjuvant treatment of
postmenopausal women with history of early-stage breast cancer
who have completed 5 years of adjuvant tamoxifen. Clin Cancer
Res. 2005;11:5671-5677.
38. MedFacts.com. MedFacts meta-analysis covering adverse side
effect reports of letrozole patients who developed lichenoid kera-
tosis. 2013 [cited 2013 3/1/2014. Available at: http://medsfacts.
com/study-LETROZOLE-causing-LICHENOIDKERATOSIS.
php. Accessed March 1, 2014.
39. Grossman ME, Warren K, Mady A, Satra KH. Lichenoid
eruption associated with ethambutol. J Am Acad Dermatol.
1995;33:675-676.
40. Choonhakarn C, Janma J. Pyrazinamide-induced lichenoid
photodermatitis. J Am Acad Dermatol. 1999;40:645-646.
41. Lehloenya RJ, Todd G, Mogotlane L, Gantsho N, Hlela C,
Dheda K. Lichenoid drug reaction to antituberculosis drugs
treated through with topical steroids and phototherapy.
J Antimicrob Chemother. 2012;67:2535-2537.
42. Byun JW, Bang CY, Choi GS, Shin J. Lichenoid eruption
associated with antituberculous drug: an unusual oral and
follicular involvement. Am J Dermatopathol. 2013;36:684-685.
43. Bakkour W, Coulson IH. GA101 (a novel anti-CD20 mono-
clonal antibody)-induced lichenoid eruption. Dermatol Ther
(Heidelb). 2012;2:3.
44. Asarch A, Gottlieb AB, Lee J, et al. Lichen planus-like erup-
tions: an emerging side effect of tumor necrosis factor-alpha
antagonists. J Am Acad Dermatol. 2009;61:104-111.
45. Moss AC, Treister NS, Marsee DK, Cheifetz AS. Clinical
challenges and images in GI. Oral lichenoid reaction in a patient
with Crohn’s disease receiving infliximab. Gastroenterology.
2007;132:488:829.
46. Mocciaro F, Orlando A, Renna S, Rizzuto MR, Cottone M. Oral
lichen planus after certolizumab pegol treatment in a patient with
Crohn’s disease. J Crohns Colitis. 2011;5:173-174.
47. Fiorentino DF. The yin and yang of TNF-a inhibition. Arch
Dermatol. 2007;143:233-236.
48. Ozkaya-Bayazit E. Specific site involvement in fixed drug
eruption. J Am Acad Dermatol. 2003;49:1003-1007.
49. Ozkaya E. Oral mucosal fixed drug eruption: characteristics and
differential diagnosis. J Am Acad Dermatol. 2013;69:e51-e58.
50. Jain VK, Dixit VB. Archana. Fixed drug eruption of the oral
mucous membrane. Ann Dent. 1991;50:9-11.
51. Pionetti CH, Kien MC, Alonso A. Fixed drug eruption due to
loratadine. Allergol Immunopathol (Madr). 2003;31:291-293.
52. Inamadar AC, Palit A, Athanikar SB, Sampagavi VV,
Deshmukh NS. Multiple fixed drug eruptions due to cetirizine.
Br J Dermatol. 2002;147:1025-1026.
53. Mahajan VK, Sharma NL, Sharma VC. Fixed drug eruption: a novel
side-effect of levocetirizine. Int J Dermatol. 2005;44:796-798.
Descargado para Anonymous User (n/a) en ClinicalKey Espanol Colombia, Ecuador & Peru Flood Relief de ClinicalKey.es por Elsevier en abril 27, 2017.
Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2017. Elsevier Inc. Todos los derechos reservados.
REVIEW ARTICLE
Yuan and Woo 43
54. Gomez-Traseira C, Rojas-Perez-Ezquerra P, Sanchez-
Morillas L, et al. Paracetamol-induced fixed drug eruption at an
unusual site. Recent Pat Inflamm Allergy Drug Discov. 2013;7:
268-270.
55. Mahendra A, Gupta S, Gupta S, Sood S, Kumar P. Oral fixed
drug eruption due to fluconazole. Indian J Dermatol Venereol
Leprol. 2006;72:391.
56. Heikkila H, Timonen K, Stubb S. Fixed drug eruption due to
fluconazole. J Am Acad Dermatol. 2000;42:883-884.
57. Alonso JC, Melgosa AC, Gonzalo MJ, Garcia CM. Fixed drug
eruption on the tongue due to clarithromycin. Contact Derma-
titis. 2005;53:121-122.
58. Gupta S, Gupta S, Mittal A, David S. Oral fixed drug eruption
caused by gabapentin. J Eur Acad Dermatol Venereol. 2009;23:
1207-1208.
59. Boulinguez S, Reix S, Bedane C, et al. Role of drug exposure in
aphthous ulcers: a case-control study. Br J Dermatol. 2000;143:
1261-1265.
60. Siegel MA, Balciunas BA. Medication can induce severe ul-
cerations. J Am Dent Assoc. 1991;122:75-77.
61. Healy CM, Thornhill MH. An association between recurrent
oro-genital ulceration and non-steroidal anti-inflammatory drugs.
J Oral Pathol Med. 1995;24:46-48.
62. Lisi P, Hansel K, Assalve D. Aphthous stomatitis induced by
piroxicam. J Am Acad Dermatol. 2004;50:648-649.
63. Trujillo MJ, de Barrio M, Rodriguez A, et al. Piroxicam-induced
photodermatitis. Cross-reactivity among oxicams. A case report.
Allergol Immunopathol (Madr). 2001;29:133-136.
64. Bagan JV, Thongprasom K, Scully C. Adverse oral reactions
associated with the COX-2 inhibitor rofecoxib. Oral Dis.
2004;10:401-403.
65. Goffin E, Pochet JM, Lejuste P, De Plaen JF. Aphtous ulcers of
the mouth associated with losartan. Clin Nephrol. 1998;50:197.
66. Martins F, de Oliveira MA, Wang Q, et al. A review of oral
toxicity associated with mTOR inhibitor therapy in cancer
patients. Oral Oncol. 2013;49:293-298.
67. de Oliveira MA, Martins EMF, Wang Q, et al. Clinical pre-
sentation and management of mTOR inhibitor-associated sto-
matitis. Oral Oncol. 2011;47:998-1003.
68. Sonis S, Treister N, Chawla S, Demetri G, Haluska F.
Preliminary characterization of oral lesions associated with
inhibitors of mammalian target of rapamycin in cancer patients.
Cancer. 2010;116:210-215.
69. Susser WS, Whitaker-Worth DL, Grant-Kels JM. Mucocuta-
neous reactions to chemotherapy. J Am Acad Dermatol.
1999;40:367-398:quiz 399-400.
70. Logan RM, Stringer AM, Bowen JM, Gibson RJ, Sonis ST,
Keefe DM. Is the pathobiology of chemotherapy-induced
alimentary tract mucositis influenced by the type of mucotoxic
drug administered? Cancer Chemother Pharmacol. 2009;63:
239-251.
71. Sonis ST. Regimen-related gastrointestinal toxicities in cancer
patients. Curr Opin Support Palliat Care. 2010;4:26-30.
72. Apostolou T, Tsagalis G, Koutroubas G, Hadjiconstantinou V,
Drakopoulos S. Mycophenolate mofetil and oral ulcerations.
Transplantation. 2004;77:1911-1912.
73. Garrigue V, Canet S, Dereure O, et al. Oral ulcerations in a renal
transplant recipient: a mycophenolate mofetil-induced compli-
cation? Transplantation. 2001;72:968-969.
74. Naranjo J, Poniachik J, Cisco D, et al. Oral ulcers produced by
mycophenolate mofetil in two liver transplant patients. Trans-
plant Proc. 2007;39:612-614.
75. Weng RR, Foster CE 3rd, Hsieh LL, Patel PR. Oral ulcers
associated with mycophenolate mofetil use in a renal transplant
recipient. Am J Health Syst Pharm. 2011;68:585-588.
ORAL MEDICINE
44 Yuan and Woo
76. Hernandez G, Jimenez C, Arriba L, Moreno E, Lucas M. Res-
olution of oral ulcerations after decreasing the dosage of tacro-
limus in a liver transplantation recipient. Oral Surg Oral Med
Oral Pathol Oral Radiol Endod. 2001;92:526-531.
77. Macario-Barrel A, Tanasescu S, Courville P, et al. Mouth ulcers
in patients receiving tacrolimus. Ann Dermatol Venereol.
2001;128:1327-1329.
78. Mignogna MD, Fortuna G, Leuci S, Pollio A, Ruoppo E.
Sunitinib adverse event: oral bullous and lichenoid mucositis.
Ann Pharmacother. 2009;43:546-547.
79. Wolf R, Brenner S. An active amide group in the molecule of
drugs that induce pemphigus: a casual or causal relationship?
Dermatology. 1994;189:1-4.
80. Vassileva S. Drug-induced pemphigoid: bullous and cicatricial.
Clin Dermatol. 1998;16:379-387.
81. Weller R, White MI. Bullous pemphigoid and penicillamine.
Clin Exp Dermatol. 1996;21:121-122.
82. Eisenberg E, Ballow M, Wolfe SH, Krutchkoff DJ, Tanzer JM.
Pemphigus-like mucosal lesions: a side effect of penicillamine
therapy. Oral Surg Oral Med Oral Pathol. 1981;51:409-414.
83. Matz H, Bialy-Golan A, Brenner S. Diclofenac: a new trigger of
pemphigus vulgaris? Dermatology. 1997;195:48-49.
84. Wijeratne C, Webster P. Risperidone and bullous pemphigoid.
Am J Psychiatry. 1996;153:735.
85. Downham TF 3rd. Spironolactone-induced lichen planus.
JAMA. 1978;240:1138.
86. Heydenreich G, Pindborg T, Schmidt H. Bullous dermatosis
among patients with chronic renal failure of high dose fruse-
mide. Acta Med Scand. 1977;202:61-64.
87. Price EJ, Venables PJ. Drug-induced lupus. Drug Saf. 1995;12:
283-290.
88. Subramanian S, Yajnik V, Sands BE, Cullen G, Korzenik JR.
Characterization of patients with infliximab-induced lupus ery-
thematosus and outcomes after retreatment with a second anti-
TNF agent. Inflamm Bowel Dis. 2011;17:99-104.
89. Perez-Alvarez R, Perez-de-Lis M, Ramos-Casals M. Biologics-
induced autoimmune diseases. Curr Opin Rheumatol. 2013;25:
56-64.
90. Ayangco L, Rogers RS 3rd. Oral manifestations of erythema
multiforme. Dermatol Clin. 2003;21:195-205.
91. Schalock PC, Brennick JB, Dinulos JG. Mycoplasma pneumo-
niae infection associated with bullous erythema multiforme.
J Am Acad Dermatol. 2005;52:705-706.
92. Auquier-Dunant A, Mockenhaupt M, Naldi L, Correia O,
Schroder W, Roujeau JC. Correlations between clinical patterns
and causes of erythema multiforme majus, Stevens-Johnson
syndrome, and toxic epidermal necrolysis: results of an inter-
national prospective study. Arch Dermatol. 2002;138:
1019-1024.
93. Edwards D, Boritz E, Cowen EW, Brown RS. Erythema mul-
tiforme major following treatment with infliximab. Oral Surg
Oral Med Oral Pathol Oral Radiol. 2013;115:e36-e40.
94. Ahdout J, Haley JC, Chiu MW. Erythema multiforme during
anti-tumor necrosis factor treatment for plaque psoriasis. J Am
Acad Dermatol. 2010;62:874-879.
95. Abou-Elhamd KE. Two cases of Stevens-Johnson syndrome
following intake of klavox with review of literature. Eur Arch
Otorhinolaryngol. 2009;266:1327-1330.
96. Kandil AO, Dvorak T, Mignano J, Wu JK, Zhu JJ. Multifocal
Stevens-Johnson syndrome after concurrent phenytoin and cra-
nial and thoracic radiation treatment, a case report. Radiat
Oncol. 2010;5:49.
97. Hilas O, Charneski L. Lamotrigine-induced Stevens-Johnson
syndrome. Am J Health Syst Pharm. 2007;64:273-275.
Descargado para Anonymous User (n/a) en ClinicalKey Espanol Colombia, Ecuador & Peru Flood Relief de ClinicalKey.es por Elsevier en abril 27, 2017.
Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2017. Elsevier Inc. Todos los derechos reservados.
OOOO
January 2015
98. Hung SI, Chung WH, Jee SH, et al. Genetic susceptibility to
carbamazepine-induced cutaneous adverse drug reactions.
Pharmacogenet Genomics. 2006;16:297-306.
99. Kulkantrakorn K, Tassaneeyakul W, Tiamkao S, et al. HLA-
B*1502 strongly predicts carbamazepine-induced Stevens-Johnson
syndrome and toxic epidermal necrolysis in Thai patients with
neuropathic pain. Pain Pract. 2012;12:202-208.
100. Hung SI, Chung WH, Liou LB, et al. HLA-B*5801 allele as a
genetic marker for severe cutaneous adverse reactions caused by
allopurinol. Proc Natl Acad Sci U S A. 2005;102:4134-4139.
101. Lonjou C, Borot N, Sekula P, et al. A European study of HLA-B
in Stevens-Johnson syndrome and toxic epidermal necrolysis
related to five high-risk drugs. Pharmacogenet Genomics.
2008;18:99-107.
102. Mallal S, Nolan D, Witt C, et al. Association between presence
of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensi-
tivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet.
2002;359:727-732.
103. Allegra A, Alonci A, Penna G, et al. Stevens-Johnson syndrome
after lenalidomide therapy for multiple myeloma: a case report
and a review of treatment options. Hematol Oncol. 2012;
30:41-45.
104. Roujeau JC, Kelly JP, Naldi L, et al. Medication use and the risk
of Stevens-Johnson syndrome or toxic epidermal necrolysis.
N Engl J Med. 1995;333:1600-1607.
105. Mockenhaupt M, Viboud C, Dunant A, et al. Stevens-Johnson
syndrome and toxic epidermal necrolysis: assessment of medi-
cation risks with emphasis on recently marketed drugs. The
EuroSCAR-study. J Invest Dermatol. 2008;128:35-44.
106. Reddy RB, Shekar PC, Chandra KL, Aravind R. Oral lesions
associated with Nevirapine-induced Stevens-Johnson syndrome
and toxic epidermal necrolysis: a report of 10 cases. J Oral
Maxillofac Pathol. 2013;17:431-435.
107. Pretel Irazabal M, Marques Martin L, Aguado Gil L, Idoate
Gastearena MA. Tranexamic acid-induced toxic epidermal
necrolysis. Ann Pharmacother. 2013;47:e16.
108. Lowndes S, Darby A, Mead G, Lister A. Stevens-Johnson
syndrome after treatment with rituximab. Ann Oncol. 2002;13:
1948-1950.
109. Treister NS, Magalnick D, Woo SB. Oral mucosal pigmentation
secondary to minocycline therapy: report of two cases and a
review of the literature. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod. 2004;97:718-725.
110. Okada N, Sato S, Sasou T, Aoyama M, Nishida K,
Yoshikawa K. Characterization of pigmented granules in min-
ocycline-induced cutaneous pigmentation: observations using
fluorescence microscopy and high-performance liquid chroma-
tography. Br J Dermatol. 1993;129:403-407.
111. Giansanti JS, Tillery DE, Olansky S. Oral mucosal pigmentation
resulting from antimalarial therapy. Oral Surg Oral Med Oral
Pathol. 1971;31:66-69.
112. Kleinegger CL, Hammond HL, Finkelstein MW. Oral mucosal
hyperpigmentation secondary to antimalarial drug therapy. Oral
Surg Oral Med Oral Pathol Oral Radiol Endod. 2000;90:
189-194.
113. Lerman MA, Karimbux N, Guze KA, Woo SB. Pigmentation of
the hard palate. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod. 2009;107:8-12.
114. Chiappinelli JA, Walton RE. Tooth discoloration resulting from
long-term tetracycline therapy: a case report. Quintessence Int.
1992;23:539-541.
115. Westbury LW, Najera A. Minocycline-induced intraoral phar-
macogenic pigmentation: case reports and review of the litera-
ture. J Periodontol. 1997;68:84-91.
OOOO
Volume 119, Number 1
116. Arora B, Kumar L, Sharma A, Wadhwa J, Kochupillai V.
Pigmentary changes in chronic myeloid leukemia patients
treated with imatinib mesylate. Ann Oncol. 2004;15:358-359.
117. Li CC, Malik SM, Blaeser BF, et al. Mucosal pigmentation
caused by imatinib: report of three cases. Head Neck Pathol.
2012;6:290-295.
118. Tadini G, D’Orso M, Cusini M, Alessi E. Oral mucosa
pigmentation: a new side effect of azidothymidine therapy in
patients with acquired immunodeficiency syndrome. Arch Der-
matol. 1991;127:267-268.
119. Ficarra G, Shillitoe EJ, Adler-Storthz K, et al. Oral melanotic
macules in patients infected with human immunodeficiency vi-
rus. Oral Surg Oral Med Oral Pathol. 1990;70:748-755.
120. Hertz RS, Beckstead PC, Brown WJ. Epithelial melanosis of the
gingiva possibly resulting from the use of oral contraceptives.
J Am Dent Assoc. 1980;100:713-714.
121. Blaya M, Saba N. Images in clinical medicine. Chemotherapy-
induced hyperpigmentation of the tongue. N Engl J Med.
2011;365:e20.
122. Alfreijat M. Tongue hyperpigmentation associated with
chemotherapy. J Community Hosp Intern Med Perspect. 2013;3.
123. Casamiquela KM, Cohen PR. Chemotherapy-associated tongue
hyperpigmentation and blue lunula. J Drugs Dermatol. 2013;12:
223-226.
124. Gonzalez-Arriagada WA, Silva AR, Vargas PA, de Almeida OP,
Lopes MA. Facial pigmentation associated with amiodarone.
Gen Dent. 2013;61:e15-e17.
125. Wolf ME, Richer S, Berk MA, Mosnaim AD. Cutaneous and
ocular changes associated with the use of chlorpromazine. Int J
Clin Pharmacol Ther Toxicol. 1993;31:365-367.
126. Pradhan S, Mishra P. Gingival enlargement in antihypertensive
medication. JNMA J Nepal Med Assoc. 2009;48:149-152.
127. Westbrook P, Bednarczyk EM, Carlson M, Sheehan H,
Bissada NF. Regression of nifedipine-induced gingival hyper-
plasia following switch to a same class calcium channel blocker,
isradipine. J Periodontol. 1997;68:645-650.
128. Seymour RA, Thomason JM, Ellis JS. The pathogenesis of drug-
induced gingival overgrowth. J Clin Periodontol. 1996;23:
165-175.
129. Brown RS, Beaver WT, Bottomley WK. On the mechanism of
drug-induced gingival hyperplasia. J Oral Pathol Med. 1991;20:
201-209.
130. Arya R, Gulati S, Kabra M, Sahu JK, Kalra V. Folic acid sup-
plementation prevents phenytoin-induced gingival overgrowth
in children. Neurology. 2011;76:1338-1343.
131. Vahabi S, Salman BN, Rezazadeh F, Namdari M. Effects of
cyclosporine and phenytoin on biomarker expressions in
gingival fibroblasts of children and adults: an in vitro study.
J Basic Clin Physiol Pharmacol. 2014;25:167-173.
132. Lee L, Miller PA, Maxymiw WG, Messner HA, Rotstein LE.
Intraoral pyogenic granuloma after allogeneic bone marrow
transplant. Report of three cases. Oral Surg Oral Med Oral
Pathol. 1994;78:607-610.
133. Al-Mohaya M, Treister N, Al-Khadra O, Lehmann L, Padwa B,
Woo SB. Calcineurin inhibitor-associated oral inflammatory
polyps after transplantation. J Oral Pathol Med. 2007;36:
570-574.
134. Kataoka M, Shimizu Y, Kunikiyo K, et al. Cyclosporin A de-
creases the degradation of type I collagen in rat gingival over-
growth. J Cell Physiol. 2000;182:351-358.
135. Schincaglia GP, Forniti F, Cavallini R, Piva R, Calura G, del
Senno L. Cyclosporin-A increases type I procollagen production
and mRNA level in human gingival fibroblasts in vitro. J Oral
Pathol Med. 1992;21:181-185.
Descargado para Anonymous User (n/a) en ClinicalKey Espanol Colombia, Ecuador & Peru Flood Relief de ClinicalKey.es por Elsevier en abril 27, 2017.
Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2017. Elsevier Inc. Todos los derechos reservados.
REVIEW ARTICLE
Yuan and Woo 45
136. Woo SB, Allen CM, Orden A, Porter D, Antin JH. Non-gingival
soft tissue growths after allogeneic marrow transplantation. Bone
Marrow Transplant. 1996;17:1127-1132.
137. Iacopino AM, Doxey D, Cutler CW, et al. Phenytoin and
cyclosporine A specifically regulate macrophage phenotype and
expression of platelet-derived growth factor and interleukin-1 in
vitro and in vivo: possible molecular mechanism of drug-induced
gingival hyperplasia. J Periodontol. 1997;68:73-83.
138. Bostanci N, Ilgenli T, Pirhan DC, et al. Relationship between IL-
1 A polymorphisms and gingival overgrowth in renal transplant
recipients receiving cyclosporin A. J Clin Periodontol. 2006;33:
771-778.
139. Morton RS, Dongari-Bagtzoglou AI. Regulation of gingival
fibroblast interleukin-6 secretion by cyclosporine A.
J Periodontol. 1999;70:1464-1471.
140. Le QT, Kim HE, Schneider CJ, et al. Palifermin reduces severe
mucositis in definitive chemoradiotherapy of locally advanced
head and neck cancer: a randomized, placebo-controlled study.
J Clin Oncol. 2011;29:2808-2814.
141. Lauritano D, Petruzzi M, Di Stasio D, Lucchese A. Clinical
effectiveness of palifermin in prevention and treatment of oral
mucositis in children with acute lymphoblastic leukaemia: a
case-control study. Int J Oral Sci. 2013;6:27-30.
142. Beaven AW, Shea TC. Recombinant human keratinocyte growth
factor palifermin reduces oral mucositis and improves patient
outcomes after stem cell transplant. Drugs Today (Barc).
2007;43:461-473.
143. Lerman MA, Treister NS. Generalized white appearance of the
oral mucosa. Hyperkeratosis secondary to palifermin. J Am Dent
Assoc. 2010;141:867-869.
144. Boer CC, Correa ME, Miranda EC, de Souza CA. Taste disor-
ders and oral evaluation in patients undergoing allogeneic he-
matopoietic SCT. Bone Marrow Transplant. 2010;45:705-711.
145. Epstein JB, Phillips N, Parry J, Epstein MS, Nevill T, Steven-
son-Moore P. Quality of life, taste, olfactory and oral function
following high-dose chemotherapy and allogeneic hematopoietic
cell transplantation. Bone Marrow Transplant. 2002:785-792.
146. Tuccori M, Lapi F, Testi A, et al. Drug-induced taste and smell
alterations: a case/non-case evaluation of an italian database of
spontaneous adverse drug reaction reporting. Drug Saf. 2011;34:
849-859.
147. Henkin RI. Drug-induced taste and smell disorders. Incidence,
mechanisms and management related primarily to treatment of
sensory receptor dysfunction. Drug Saf. 1994;11:318-377.
148. Sekulic A, Migden MR, Oro AE, et al. Efficacy and safety of
vismodegib in advanced basal-cell carcinoma. N Engl J Med.
2012;366:2171-2179.
149. Han Y, Smith MT. Pathobiology of cancer chemotherapy-
induced peripheral neuropathy (CIPN). Front Pharmacol.
2013;4:156.
150. Hershman DL, Weimer LH, Wang A, et al. Association between
patient reported outcomes and quantitative sensory tests for
measuring long-term neurotoxicity in breast cancer survivors
treated with adjuvant paclitaxel chemotherapy. Breast Cancer
Res Treat. 2011;125:767-774.
151. Park SB, Goldstein D, Krishnan AV, et al. Chemotherapy-
induced peripheral neurotoxicity: a critical analysis. CA Cancer
J Clin. 2013;63:419-437.
152. Dorchin M, Masoumi Dehshiri R, Soleiman S, Manashi M.
Evaluation of neuropathy during intensive vincristine chemo-
therapy for non-Hodgkin’s lymphoma and acute lymphoblastic
leukemia. Iran J Ped Hematol Oncol. 2013;3:138-142.
153. Dixit G, Dhingra A, Kaushal D. Vincristine induced cranial
neuropathy. J Assoc Physicians India. 2012;60:56-58.
ORAL MEDICINE
46 Yuan and Woo
154. Burns BV, Shotton JC. Vocal fold palsy following vinca alka-
loid treatment. J Laryngol Otol. 1998;112:485-487.
155. Naithani R, Dolai TK, Kumar R. Bilateral vocal cord paralysis
following treatment with vincristine. Indian Pediatr. 2009;46:
68-69.
156. Lipworth AD, Robert C, Zhu AX. Hand-foot syndrome (hand-
foot skin reaction, palmar-plantar erythrodysesthesia): focus on
sorafenib and sunitinib. Oncology. 2009;77:257-271.
157. Lee WJ, Lee JL, Chang SE, et al. Cutaneous adverse effects in
patients treated with the multitargeted kinase inhibitors sorafenib
and sunitinib. Br J Dermatol. 2009;161:1045-1051.
158. Kollmannsberger C, Bjarnason G, Burnett P, et al. Sunitinib in
metastatic renal cell carcinoma: recommendations for manage-
ment of noncardiovascular toxicities. Oncologist. 2011;16:
543-553.
159. Ruggiero SL, Mehrotra B. Bisphosphonate-related osteonecrosis
of the jaw: diagnosis, prevention, and management. Annu Rev
Med. 2009;60:85-96.
160. Otto S, Baumann S, Ehrenfeld M, Pautke C. Successful surgical
management of osteonecrosis of the jaw due to RANK-ligand
inhibitor treatment using fluorescence guided bone resection.
J Craniomaxillofac Surg. 2013;41:694-698.
161. Rachner TD, Platzbecker U, Felsenberg D, Hofbauer LC.
Osteonecrosis of the jaw after osteoporosis therapy with deno-
sumab following long-term bisphosphonate therapy. Mayo Clin
Proc. 2013;88:418-419.
162. Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonate-
induced exposed bone (osteonecrosis/osteopetrosis) of the jaws:
risk factors, recognition, prevention, and treatment. J Oral
Maxillofac Surg. 2005;63:1567-1575.
163. Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL. Osteo-
necrosis of the jaws associated with the use of bisphosphonates:
a review of 63 cases. J Oral Maxillofac Surg. 2004;62:527-534.
164. Woo SB, Hellstein JW, Kalmar JR. Narrative [corrected] review:
Bisphosphonates and osteonecrosis of the jaws. Ann Intern Med.
2006;144:753-761.
165. Woo SB, Mawardi H, Treister N. Comments on Osteonecrosis of
the jaws in intravenous bisphosphonate use: proposal for a modi-
fication of the clinical classification. Oral Oncol. 2009;45:740.
166. Ruggiero SL, Dodson TB, Assael LA, Landesberg R, Marx RE,
Mehrotra B. American Association of Oral and Maxillofacial
Surgeons position paper on bisphosphonate-related osteonec-
rosis of the jawsd2009 update. J Oral Maxillofac Surg.
2009;67:2-12.
167. Wood J, Bonjean K, Ruetz S, et al. Novel antiangiogenic effects
of the bisphosphonate compound zoledronic acid. J Pharmacol
Exp Ther. 2002;302:1055-1061.
168. Estilo CL, Fornier M, Farooki A, Carlson D, Bohle G 3rd,
Huryn JM. Osteonecrosis of the jaw related to bevacizumab.
J Clin Oncol. 2008;26:4037-4038.
169. Guarneri V, Miles D, Robert N, et al. Bevacizumab and osteo-
necrosis of the jaw: incidence and association with bisphosph-
onate therapy in three large prospective trials in advanced breast
cancer. Breast Cancer Res Treat. 2010;122:181-188.
170. Katsenos S, Christophylakis C, Psathakis K. Osteonecrosis of
the jaw in a patient with advanced non-small-cell lung cancer
receiving bevacizumab. Arch Bronconeumol. 2012;48:218-219.
171. Hoefert S, Eufinger H. Sunitinib may raise the risk of
bisphosphonate-related osteonecrosis of the jaw: presentation of
three cases. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod. 2010;110:463-469.
172. Koch FP, Walter C, Hansen T, Jager E, Wagner W. Osteonec-
rosis of the jaw related to sunitinib. Oral Maxillofac Surg.
2011;15:63-66.
Descargado para Anonymous User (n/a) en ClinicalKey Espanol Colombia, Ecuador & Peru Flood Relief de ClinicalKey.es por Elsevier en abril 27, 2017.
Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2017. Elsevier Inc. Todos los derechos reservados.
OOOO
January 2015
173. Fleissig Y, Regev E, Lehman H. Sunitinib related osteonecrosis
of jaw: a case report. Oral Surg Oral Med Oral Pathol Oral
Radiol. 2012;113:e1-e3.
174. Smidt-Hansen T, Folkmar TB, Fode K, Agerbaek M,
Donskov F. Combination of zoledronic acid and targeted ther-
apy is active but may induce osteonecrosis of the jaw in patients
with metastatic renal cell carcinoma. J Oral Maxillofac Surg.
2013;71:1532-1540.
175. Agrillo A, Nastro Siniscalchi E, Facchini A, Filiaci F, Ungari C.
Osteonecrosis of the jaws in patients assuming bisphosphonates
and sunitinib: two case reports. Eur Rev Med Pharmacol Sci.
2012;16:952-957.
176. Demetri GD, van Oosterom AT, Garrett CR, et al. Efficacy and
safety of sunitinib in patients with advanced gastrointestinal
stromal tumour after failure of imatinib: a randomised controlled
trial. Lancet. 2006;368:1329-1338.
177. Christodoulou C, Pervena A, Klouvas G, et al. Combination of
bisphosphonates and antiangiogenic factors induces osteonec-
rosis of the jaw more frequently than bisphosphonates alone.
Oncology. 2009;76:209-211.
178. Okui T, Shimo T, Fukazawa T, et al. Antitumor effect of tem-
sirolimus against oral squamous cell carcinoma associated with
bone destruction. Mol Cancer Ther. 2010;9:2960-2969.
179. Giancola F, Campisi G, Russo LL, Muzio LL, Di Fede O.
Osteonecrosis of the jaw related to everolimus and bisphosph-
onate: a unique case report? Ann Stomatol (Roma). 2013;
4:20-21.
180. Scully C, el-Kabir M, Samaranayake LP. Candida and oral
candidosis: a review. Crit Rev Oral Biol Med. 1994;5:125-157.
181. Dreizen S, Keating MJ, Beran M. Orofacial fungal infections.
Nine pathogens that may invade during chemotherapy. Postgrad
Med. 1992;91:349-350, 353-354, 357-360 passim.
182. Al Akhrass F, Debiane L, Abdallah L, et al. Palatal mucormy-
cosis in patients with hematologic malignancy and stem cell
transplantation. Med Mycol. 2011;49:400-405.
183. Marsot-Dupuch K, Quillard J, Meyohas MC. Head and neck
lesions in the immunocompromised host. Eur Radiol. 2004;14:
E155-E167.
184. Schubert MM. Oral manifestations of viral infections in immu-
nocompromised patients. Curr Opin Dent. 1991;1:384-397.
185. Triantos D, Porter SR, Scully C, Teo CG. Oral hairy leukopla-
kia: clinicopathologic features, pathogenesis, diagnosis, and
clinical significance. Clin Infect Dis. 1997;25:1392-1396.
186. Pinheiro RS, de Franca TR, Rocha B, et al. Human papilloma-
virus coinfection in the oral cavity of HIV-infected children.
J Clin Pathol. 2011;64:1083-1087.
187. Samonis G, Mantadakis E, Maraki S. Orofacial viral infections
in the immunocompromised host. Oncol Rep. 2000;7:
1389-1394.
188. Stoopler ET, Greenberg MS. Update on herpesvirus infections.
Dent Clin North Am. 2003;47:517-532.
189. Deepak P, Stobaugh DJ, Ehrenpreis ED. Infectious complica-
tions of TNF-alpha inhibitor monotherapy versus combination
therapy with immunomodulators in inflammatory bowel disease:
analysis of the Food and Drug Administration Adverse Event
Reporting System. J Gastrointestin Liver Dis. 2013;22:269-276.
190. Delabaye I, De Keyser F. 74-wk follow-up of safety of inflix-
imab in patients with refractory rheumatoid arthritis. Arthritis
Res Ther. 2010;12:R121.
191. Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL,
Montori V. Anti-TNF antibody therapy in rheumatoid arthritis
and the risk of serious infections and malignancies: systematic
review and meta-analysis of rare harmful effects in randomized
controlled trials. JAMA. 2006;295:2275-2285.
OOOO
Volume 119, Number 1
192. Salvana EM, Salata RA. Infectious complications associated
with monoclonal antibodies and related small molecules. Clin
Microbiol Rev. 2009;22:274-290, Table of Contents.
193. Hom KA, Hirsch R, Elluru RG. Antihypertensive drug-induced
angioedema causing upper airway obstruction in children. Int J
Pediatr Otorhinolaryngol. 2012;76:14-19.
194. Rafii MS, Koenig M, Ziai WC. Orolingual angioedema associ-
ated with ACE inhibitor use after rtPA treatment of acute stroke.
Neurology. 2005;65:1906.
195. Shino M, Takahashi K, Murata T, Iida H, Yasuoka Y,
Furuya N. Angiotensin II receptor blocker-induced angioe-
dema in the oral floor and epiglottis. Am J Otolaryngol.
2011;32:624-626.
196. Southward J, Irvine E, Rabinovich M. Probable amlodipine-
induced angioedema. Ann Pharmacother. 2009;43:772-776.
197. Ruscin JM, Page RL 2nd, Scott J. Hydrochlorothiazide-induced
angioedema in a patient allergic to sulfonamide antibiotics: ev-
idence from a case report and a review of the literature. Am J
Geriatr Pharmacother. 2006;4:325-329.
198. Fischer TC, Worm M, Groneberg DA. Clopidogrel-associated
angioedema. Am J Med. 2003;114:77-78.
199. Nisly SAAK, Knight TB. Simvastatin: a risk factor for angioe-
dema? J Pharmacy Technol. 2013;29:149-152.
200. Liebhaber MI, Wright RS, Gelberg HJ, Dyer Z, Kupperman JL.
Polymyalgia, hypersensitivity pneumonitis and other reactions
in patients receiving HMG-CoA reductase inhibitors: a report of
ten cases. Chest. 1999;115:886-889.
201. Insert P. Lipitor (atorvastatin). 2009. Available at: http://www.
accessdata.fda.gov/drugsatfda_docs/label/2009/020702s057lbl.
pdf. Accessed April 1, 2014.
202. Hampson JP, Smith D, Cowell R, Baker A. Hypotension and
eosinophilia with atorvastatin. Pharm World Sci. 2005;27:
279-280.
203. Bagg A, Dunphy CH. Immunosuppressive and immunomodu-
latory therapy-associated lymphoproliferative disorders. Semin
Diagn Pathol. 2013;30:102-112.
204. Hoshida Y, Xu JX, Fujita S, et al. Lymphoproliferative disorders
in rheumatoid arthritis: clinicopathological analysis of 76 cases
in relation to methotrexate medication. J Rheumatol. 2007;34:
322-331.
205. Hanakawa H, Orita Y, Sato Y, Uno K, Nishizaki K, Yoshino T.
Large ulceration of the oropharynx induced by methotrexate-
associated lymphoproliferative disorders. Acta Med Okayama.
2013;67:265-269.
206. Ichikawa A, Arakawa F, Kiyasu J, et al. Methotrexate/iatrogenic
lymphoproliferative disorders in rheumatoid arthritis: histology,
Epstein-Barr virus, and clonality are important predictors of
disease progression and regression. Eur J Haematol. 2013;91:
20-28.
207. Kikuchi K, Miyazaki Y, Tanaka A, et al. Methotrexate-related
Epstein-Barr virus (EBV)-associated lymphoproliferative
disorderdso-called “Hodgkin-like lesion”dof the oral cavity in
a patient with rheumatoid arthritis. Head Neck Pathol. 2010;4:
305-311.
Descargado para Anonymous User (n/a) en ClinicalKey Espanol Colombia, Ecuador & Peru Flood Relief de ClinicalKey.es por Elsevier en abril 27, 2017.
Para uso personal exclusivamente. No se permiten otros usos sin autorización. Copyright ©2017. Elsevier Inc. Todos los derechos reservados.
REVIEW ARTICLE
Yuan and Woo 47
208. Kalantzis A, Marshman Z, Falconer DT, Morgan PR, Odell EW.
Oral effects of low-dose methotrexate treatment. Oral Surg Oral
Med Oral Pathol Oral Radiol Endod. 2005;100:52-62.
209. Niwa Y, Terashima T, Sumi H. Topical application of the
immunosuppressant tacrolimus accelerates carcinogenesis in
mouse skin. Br J Dermatol. 2003;149:960-967.
210. Mattsson U, Magnusson B, Jontell M. Squamous cell carcinoma
in a patient with oral lichen planus treated with topical appli-
cation of tacrolimus. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod. 2010;110:e19-e25.
211. Becker JC, Houben R, Vetter CS, Brocker EB. The carcinogenic
potential of tacrolimus ointment beyond immune suppression: a
hypothesis creating case report. BMC Cancer. 2006;6:7.
212. Wimmer CD, Angele MK, Schwarz B, et al. Impact of cyclo-
sporine versus tacrolimus on the incidence of de novo malig-
nancy following liver transplantation: a single center experience
with 609 patients. Transpl Int. 2013;26:999-1006.
213. Berger TG, Duvic M, Van Voorhees AS, VanBeek MJ,
Frieden IJ. The use of topical calcineurin inhibitors in derma-
tology: safety concerns. Report of the American Academy of
Dermatology Association Task Force. J Am Acad Dermatol.
2006;54:818-823.
214. Tennis P, Gelfand JM, Rothman KJ. Evaluation of cancer risk
related to atopic dermatitis and use of topical calcineurin in-
hibitors. Br J Dermatol. 2011;165:465-473.
215. Fischer G, Bradford J. Topical immunosuppressants, genital
lichen sclerosus and the risk of squamous cell carcinoma: a case
report. J Reprod Med. 2007;52:329-331.
216. Langeland T, Engh V. Topical use of tacrolimus and squamous
cell carcinoma on the penis. Br J Dermatol. 2005;152:183-185.
217. Mabrouk D, Gurcan HM, Keskin DB, Christen WG,
Ahmed AR. Association between cancer and immunosuppres-
sive therapydanalysis of selected studies in pemphigus and
pemphigoid. Ann Pharmacother. 2010;44:1770-1776.
218. Leombruno JP, Einarson TR, Keystone EC. The safety of anti-
tumour necrosis factor treatments in rheumatoid arthritis: meta
and exposure-adjusted pooled analyses of serious adverse
events. Ann Rheum Dis. 2009;68:1136-1145.
219. Baecklund E, Backlin C, Iliadou A, et al. Characteristics of
diffuse large B cell lymphomas in rheumatoid arthritis. Arthritis
Rheum. 2006;54:3774-3781.
220. Mawardi H, Elad S, Correa ME, et al. Oral epithelial dysplasia
and squamous cell carcinoma following allogeneic hematopoi-
etic stem cell transplantation: clinical presentation and treatment
outcomes. Bone Marrow Transplant. 2011;46:884-891.
Reprint requests:
Anna Yuan
Division of Oral Medicine and Dentistry
Brigham and Women’s Hospital
Boston, MA
annayuan@post.harvard.edu