Livedoid Skin Reaction Probably Due to Imatinib Therapy
M Covadonga Martínez-González, Jesús del Pozo, María Teresa Yebra-Pimentel, Mónica Pérez,
Manuel Almagro, and Eduardo Fonseca
hronic myeloid leukemia (CML) is
C a clonal disorder occurring in a
hematopoietic stem cell in which cells of
OBJECTIVE: To report 3 cases of skin rash with a peculiar livedoid pattern that
were probably associated with imatinib therapy.
CASE SUMMARY: In the first case, a 74-year-old male diagnosed with Philadelphia
the myeloid lineage undergo massive chromosome-positive (Ph+) chronic myeloid leukemia (CML), treated with
clonal expansion. Its incidence is about 1.3 imatinib 400 mg/day, developed a skin eruption with a livedoid pattern. Systemic
cases per 100 000 people. Current thera- corticosteroids were started, and skin lesions improved. The second case
pies include allogeneic bone marrow involved a 66-year-old male with Ph+ CML who was treated with imatinib 600
mg/day. After initiation of this treatment, he developed a skin rash with a livedoid
transplantation and drug treatments in-
pattern. The drug treatment was discontinued and then reintroduced. Topical
cluding chemotherapy and interferon alfa corticosteroid treatment was started, resulting in total remission of the skin
(IFN-α). To date, allogeneic stem cell lesions. When the imatinib dose was progressively reintroduced, the skin lesions
transplantation represents the only treat- recurred. The patient died as a result of the progression of his disease. In the
ment for potential cure of the disease, but third case, a 43-year-old male with Ph+ acute lymphoblastic leukemia was
it can be used in only a minority of pa- treated with imatinib 600 mg/day. After a few days of treatment, the patient
developed a skin rash with a livedoid pattern. He died as a result of probable
tients. There is no single standard therapy
for blast crisis in patients with CML.1,2
DISCUSSION: Imatinib is a tyrosine kinase receptor inhibitor that inhibits BCR/ABL
Philadelphia chromosome-positive tyrosine kinase. There have been several published articles on cutaneous
(Ph+) myeloproliferative disorder results adverse reactions related to imatinib therapy. The most common cutaneous
from the reciprocal translocation between adverse event of imatinib is a rash with variable clinical presentation. The
chromosomes 22 and 9. This translocation Naranjo probability scale indicated a probable relationship between imatinib and
relocates an oncogen called ABL in the the rash in all 3 cases reported here.
BCR region. The BCR/ABL fusion gene CONCLUSIONS: Adverse reactions to imatinib that affect the skin occur frequently.
They are strongly dose dependent, self-limiting, or easily managed by lowering
encodes a protein that regulates tyrosine
the dose of imatinib and, if necessary, prescribing short-term therapy with a
kinase activity. This process will lead to systemic corticosteroid. Clinicians should monitor patients taking imatinib and
the development of CML phenotype. institute treatment quickly if a rash develops.
This translocation can also be present in KEY WORDS: imatinib, livedoid pattern, skin rash.
other hematologic diseases, such as some
Ann Pharmacother 2007;41:148-52.
cases of acute lymphoblastic leukemia
Published Online, 26 Dec 2006, www.theannals.com, DOI 10.1345/aph.1H304
Imatinib mesylate is an oral antineo-
plastic agent that selectively inhibits BCR/ABL tyrosine the tyrosine kinase activity of c-kit (stem-cell factor recep-
kinase activity of BCR/ABL fusion, the product of the tor) and platelet-derived growth factor receptor (PDGFR).
Philadelphia chromosome.1-3 Imatinib is a promising drug Subsequently, imatinib has been used for FIP1l1-PDGFR[α]+
currently considered in the treatment of serious diseases, mast cell disease, hypereosinophilic syndrome, and der-
4-6 matofibrosarcoma protuberans. It does not seem to be effec-
such as CML. It has also proved very active in blocking
tive for melanoma.7
The Food and Drug Administration has approved the
Author information provided at the end of the text. use of imatinib for the following indications: treatment of
148 I The Annals of Pharmacotherapy I 2007 January, Volume 41 www.theannals.com
adults with Ph+ CML in the chronic phase; treatment of branes, nails, and scalp were not affected. Because of the
patients with Ph+ CML in blast crisis, accelerated phase, time–event relationship between the start of imatinib and
or chronic phase after failure of interferon therapy; treat- development of the rash, there was a suspicion of toxico-
ment of pediatric patients with Ph+ CML in the chronic dermia. A skin biopsy showed irregular thinning epider-
phase recurring after stem-cell transplant or who are resis- mis, with absence of granular cell layer and light spongio-
tant to IFN-α therapy; and treatment of Kit-positive sis. The papillary dermis showed hyalinization with highly
(CD117) unresectable and/or metastatic malignant gas- dilated blood vessels, perivascular edema, and infiltrate
trointestinal (GI) stromal tumors. Moreover, imatinib has mononuclear cells, occasionally in spindle shape. There
been used for several unapproved indications. was no hematic extravasation, fibrin thrombus, or poly-
Adverse reactions related to imatinib are frequent but morphonuclear cell infiltration.
generally mild to moderate. Only in rare cases are patients It was not necessary to discontinue imatinib therapy;
with adverse drug reactions required to discontinue thera- however, during the patient’s hospitalization, systemic cor-
py. These reactions may vary from hematologic, skin, GI, ticosteroid therapy was started concomitantly (prednisone
endocrine/metabolic, neuromuscular, and skeletal adverse 1 mg/kg, during 10 days in descending doses). After 8
effects.8,9 days of treatment, the skin lesions were substantially im-
Imatinib has been associated with a high incidence of proved and the patient was discharged home. During the
skin reactions, and a wide range of 7– 69% of the drug’s follow-up visits several months later, no new lesions were
adverse effects involve the skin.10-12 These skin reactions observed, although an imatinib maintenance dose of 400
are usually dose dependent and not life-threatening; they mg/day was continued. All cutaneous lesions were healed.
do not require that therapy be stopped.
We report 3 cases of dose-related systemic skin reac- CASE 2
tions to imatinib and discuss the pathogenic mechanisms
of these reactions. A 66-year-old male was diagnosed in 1989 with Ph+
CML. He did not have any other significant medical histo-
ry or any kind of drug or food allergy. The patient had
been treated with variable doses and combinations of
CASE 1 busulfan, hydroxyurea, allopurinol, and INF-α. He was on
continuous IFN-α therapy for 7 years, and the treatment
A 74-year-old male was diagnosed in 1983 with Ph+ was discontinued when the patient developed serious toxi-
CML. Other significant medical history included type 2 di- city with distal ischemic and peripheral neuropathy of low-
abetes mellitus, acute nephritic colic, and osteomuscular er extremities without any skin reaction. He was not re-
pain. He did not have any history of allergy to food or ceiving a high dose of INF-α.
drugs. The patient had been treated over the past several In December 1997, the patient suffered an exacerbation
years with aspirin for prevention of stroke, codeine for of his blast crisis. This required an increase in the hydrox-
treatment of osteomuscular pain, and insulin for diabetes yurea dose of up to 2500 mg/day. In February 2002, ima-
mellitus. Variable doses of hydroxyurea were prescribed, tinib treatment was initiated at 100 mg/day and increased
according to the stage of the hematologic disease, with oc- to 400 mg/day, with gradual discontinuation of hydrox-
casional use of allopurinol. Subsequently, his disease status yurea. His hepatic status was normal, and no CYP3A4 in-
was stable for a long time and did not require any further hibitors were concomitantly used. In March 2002, the
therapy. treatment was increased to 600 mg/day. In May 2002, he
In September 2002, the patient developed a blast crisis. presented with an erythematous, itching skin reaction that
In January 2003, he started imatinib 400 mg/day for treat- had developed on initiation of imatinib therapy; the clini-
ment of his disease. Three weeks later, a slightly itchy gen- cians reduced the dose to 400 mg/day and referred the pa-
eralized cutaneous exanthema, without systemic symp- tient to the dermatology department.
toms, developed. Oral and genital mucosa were not in- The skin examination showed slightly scaly cutaneous
volved. Given these symptoms, the patient was referred to erythematous lesions with plaques on the patient’s thighs
the dermatology department for further evaluation of his that were associated with livedoid pattern (Figure 1). The
skin rash. mucous membranes were spared. We suspected a drug-in-
The skin examination showed generalized exanthema, duced skin reaction. A biopsy of skin taken from the right
more intense on the inferior part of the trunk and the supe- thigh showed a hyperplastic epidermis, with continuous
rior part of the lower extremities. On the abdomen, back, parakeratosis, focal granulation tissue, and spongiosis. At
and buttocks, the skin eruption showed a livedoid pattern, the same time, a lymphocytic exocytosis was noticed,
whereas in the lower extremities, the presentation was sim- which causes the disappearance of the dermo-epidermal
ilar to that of erythema multiforme. The mucosal mem- junction. There were necrotic keratinocytes inside the epi-
www.theannals.com The Annals of Pharmacotherapy I 2007 January, Volume 41 I 149
MC Martínez-González et al.
dermis. Papillary dermis showed ecstatic blood vessels CASE 3
(Figure 2). These histological features were considered
A 43-year-old male without other significant past medi-
compatible with the diagnostic criteria of toxicodermia.
cal history or allergies had been diagnosed with Ph+ ALL
Imatinib was discontinued for 2 days and reintroduced
in 2000. At that time, he was treated with a chemotherapy
at low doses (100 mg/day), to be gradually increased. Top-
regimen (PETHEMA-LAL/AR 93, that included vin-
ical corticosteroid therapy was started and resulted in heal-
cristine, daunorubicin, L-asparaginase, cyclophosphamide,
ing of the skin lesions. When the imatinib dose was in- prednisone, and intrathecal treatment with methotrexate,
creased to 600 mg/day to control the blast crisis, the skin cytarabine, and hydrocortisone). That same year, the pa-
lesions recurred, but they spontaneously cleared without tient underwent hematologic autotransplantation for fur-
adjuvant treatment. The imatinib dose was increased to ther treatment of his illness. His disease relapsed in 2002.
800 mg/day to control a new blast crisis that had begun in At that time, imatinib treatment was initiated at a dose of
January 2003. While receiving this dose, the patient devel- 600 mg daily, resulting in a generalized (especially on
oped conjunctival chemosis, periorbital edema, and serious thighs) exanthematous erythematous skin reaction with a
eyelid edema; the dose was reduced to 600 mg/day. One livedoid pattern within a few days. The microscopic de-
month later, the dose was increased to 800 mg/day due to scription of the skin biopsy was consistent with diagnosis
severe deterioration of his hematologic disease. Within 2 criteria of toxicodermia.
weeks, the patient developed significant edema in the low- The patient quickly developed mucosa and skin jaun-
er extremities without any improvement after furosemide dice, severe pancytopenia, and also renal, hepatic, and pul-
treatment (40 mg/day for 15 days). The patient died in monary failure. He died one month after the initiation of ima-
May 2003 due to the progression of the hematologic dis- tinib treatment as a result of multiorgan failure secondary to
ease with secondary pulmonary infiltration. probable septic shock that was likely initiated by a severe or-
ganizing pneumonia associated with serious pancytopenia.
Cultures taken from blood and bronchial aspiration showed
Staphylococcus epidermidis and Enterobacter cloacae.
Dermatologic adverse effects of imatinib vary between
minor problems and serious cutaneous symptoms that, al-
though rare, can be life-threatening (Table 1).7-19 In one re-
port, skin adverse reactions occurred in 21% of patients
treated with imatinib.13 However, a prospective study that
included 54 patients found a greater incidence of rash
(66%) in patients who received imatinib; 40% of these pa-
tients developed pruritus and 35% developed edema.14 Cu-
Figure 1. Slightly scaly cutaneous erythematous lesions with plaques
that were associated with livedoid pattern on the patient’s thighs. taneous rash is the most frequent skin adverse event related
to imatinib treatment.
Several types of rash related to imatinib treatment have
been described, including psoriasiform, purpuric, macular,
papular, maculopapular, exfoliative dermatitis, and pustu-
lous nonfollicular, usually accompanied by edema and/or
severe pruritus.2,12-14 To our knowledge, as of December
16, 2006, the livedoid pattern of rash that occurred in our
patients has not been previously described. The use of the
Naranjo probability scale indicated a probable relationship
between the incidence of the livedoid skin rash and the use
of imatinib therapy in all 3 of the patients reported here.20
It has been established that these rashes are mediated by
a pharmacologic effect and that their severity correlates
with the dose. Their occurrence early during therapy may
suggest the existence of hypersensitivity in addition to a
pharmacologic effect of imatinib. Imatinib mediates inhi-
Figure 2. Papillary dermis showing ecstatic blood vessels. bition of PDGF receptors (expressed on blood vessels and
150 I The Annals of Pharmacotherapy I 2007 January, Volume 41 www.theannals.com
Livedoid Skin Reaction Associated with Imatinib
negatively regulating transcapillary transport) that may Conclusions
cause an increase of dermal interstitial fluid pressure, in-
ducing edema, erythema, and desquamation. PDGF recep- Adverse reactions to imatinib that affect the skin occur
tors are expressed in most dermal cells, but a role for ima- frequently. They are strongly dose dependent, self-limiting,
tinib-mediated inhibition of these receptors is not known.13 or easily managed by lowering the dose of imatinib and, if
The adverse skin reactions to imatinib have 3 important necessary, prescribing short-term therapy with a systemic
characteristics. The first one is that these effects are strong- corticosteroid. Clinicians should monitor patients taking
ly dose dependent (suggesting a cutaneous reactivity pat- imatinib and institute treatment quickly if a rash develops.
tern different from allergic hypersensitivity).13-15 Druker et
M Covadonga Martínez-González MD, Medical Resident, Der-
al.2,3 found that rashes developed primarily in patients who matology Department, Juan Canalejo Hospital, A Coruña, Spain
exceeded a daily imatinib dose of 600 mg; this dose seems Jesús del Pozo MD, Clinical Specialist, Dermatology Department,
to be the threshold dose for serious skin adverse reactions. Juan Canalejo Hospital
María Teresa Yebra-Pimentel MD, Clinical Specialist, Pathology
The second characteristic is that skin adverse reactions are Department, Juan Canalejo Hospital
self-limiting or easily managed by decreasing the initial Mónica Pérez MD, Clinical Specialist, Dermatology Department,
dose of imatinib, and, if necessary, treated with oral corti- Juan Canalejo Hospital
Manuel Almagro MD, Professor, Dermatology Department, Juan
costeroids. Generally, after discontinuation and gradual Canalejo Hospital
reintroduction of imatinib, the standard dose can be Eduardo Fonseca MD, Professor and Director, Dermatology De-
reached without recurrence of rashes.10 The third character- partment, Juan Canalejo Hospital
istic of imitanib-associated skin reactions is that the mu- Reprints: Dr. Martínez-González, Servicio de Dermatología, Com-
plejo Hospitalario Universitario Juan Canalejo, Xubias de Arriba 84,
cous membranes are usually spared. 15006 A Coruña, España, fax 981205375, email@example.com
1. Cervantes F, Hernandez-Boluda JC, Odriozola J, et al. Imatinib mesylate
Table 1. Skin Reactions Associated with Imatinib7-19 (STI571) treatment in patients with chronic-phase chronic myelogenous
Acute, generalized exanthematic pustulosis leukaemia previously submitted to autologous stem cell transplantation.
Baboon-like exanthemas Br J Haematol 2003;120:500-4.
Cutaneous lichenoid eruptions and oral erosive lichen planus–like 2. Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM. Effi-
lesions cacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase
Dose-related cutaneous rash (livedoid pattern in our pts.) in chronic myeloid leukaemia. N Engl J Med 2001;344:1031-7.
Eccrine squamous syringometaplasia 3. Druker BJ, Sawyers CL, Kantarjian H, et al. Activity of a specific inhibitor
Epstein-Barr virus–positive cutaneous B-cell lymphoproliferative of the blast crisis of chronic myeloid leukemia and acute lymphoblastic
disease leukemia with the Philadelphia chromosome. N Engl J Med 2001;344:
Erythema multiforme, disseminated folliculitis, and oral erosive lesions 1038- 42.
4. Ikegame K, Mukouchi C, Kunitomi A, et al. Successful treatment of
Exacerbation of preexisting chronic psoriasis
bcr/abl-positive acute mixed lineage leukemia by unmanipulated bone
marrow transplantation from an HLA-haploidentical (3-antigen-mis-
matched) cousin. Bone Marrow Transplant 2003;31:1165-8.
Itching, xerosis, and desquamation
5. Berger U, Hehlmann R. Imatinib—new, molecular therapeutic possibility in
Neutrophilic dermatosis chronic myeloid leukemia. The IRIS Study. Internist (Berl) 2004;45:102-3.
neutrophilic eccrine hidradenitis 6. O’Brien SG, Guilhot F, Larson RA, et al. IRIS Investigators. Imatinib com-
Sweet’s syndrome pared with interferon and low-dose cytarabine for newly diagnosed chron-
Night sweats ic-phase chronic myeloid leukemia. N Engl J Med 2003;348:994-1004.
Periorbital, peripheral, or generalized edema 7. Schienfeld N. A comprehensive review of imatinib mesylate (Gleevec)
Photosensitivity for dermatological diseases. J Drugs Dermatol 2006;5:117-22.
Pigmentary alterations 8. Severino G, Chillotti C, De Lisa R, Del Zompo M, Ardau R. Adverse re-
hair discoloration actions during imatinib and lansoprazole treatment in gastrointestinal
hyper- and hypopigmentation stromal tumors. Ann Pharmacother 2005;39:162- 4. Epub 2004 Nov 16.
Pityriasis rosea–like and other pityriasiform eruptions DOI 10.1345/aph1.E127
Porphyria cutanea tarda (reactivation or induction) 9. Ugurel S, Hildenbrand R, Dippel E, Hochhaus A, Schadendorf D. Dose-de-
Possible induction of pendent severe cutaneous reactions to imatinib. Br J Cancer 2003;88:1157-
follicular mucinosis 9.
hyaline cell syringomas
10. Breccia M, Carmosino I, Russo E, Morano SG, Latagliata R, Alimena G.
Early and tardive skin adverse events in chronic myeloid leukaemia pa-
pseudolymphoma-type drug eruptions
tients treated with imatinib. Eur J Haematol 2005;74:121-3.
squamous cell carcinomas
11. Roux C, Boisseau-Garsaud AM, Saint-Cyr I, Helenon R, Quist D, De-
launay C. Lichenoid cutaneous reaction to imatinib. Ann Dermatol Ve-
Purpuric vasculitis and mycosis fungoides–like reactions
Small vessel vasculitis
Stevens–Johnson syndrome 12. Scheinfeld N. Imatinib mesylate and dermatology part 2: a review of the
Toxic epidermal necrolysis cutaneous side effects of imatinib mesylate. J Drugs Dermatol 2006;5:
www.theannals.com The Annals of Pharmacotherapy I 2007 January, Volume 41 I 151
MC Martínez-González et al.
13. Brouard M, Saurat JH. Cutaneous reactions to STI571. N Engl J Med efecto cutáneo adverso más frecuente es un rash con presentación clínica
2001;345:618-9. variable. Presentamos 3 casos de rash cutáneo livedoide probablemente
14. Valeyrie L, Bastuji-Garin S, Revuz J, et al. Adverse cutaneous reactions debido al tratamiento con imatinib. La escala de probabilidad de
to imatinib (STI571) in Philadelphia chromosome–positive leukemias: a Naranjo para reacciones adversas a fármacos (ADR) indicó una relación
prospective study of 54 patients. J Am Acad Dermatol 2003;48:201-6. ‘probable’ en los 3 casos.
15. Drummond A, Micallef-Eynaud P, Douglas WS, Hay I, Holyoake TL, CONCLUSIONES: Aunque las reacciones cutáneas adversas debidas al
Drummond MW. A spectrum of skin reactions caused by the tyrosine ki- tratamiento con imatinib son frecuentes, suelen ser dosis-dependientes,
nase inhibitor imatinib mesylate (STI 571, Glivec). Br J Haematol 2003; autolimitadas o fácilmente manejadas con una dosis inicial baja de
120:911-3. imatinib y, si es necesario, con un ciclo corto de corticoides sistémicos.
16. Hamm M, Touraud JP, Mannone L, Klisnick J, Ponnelle T, Lambert D.
No obstante, debemos ser cautos cuando ocurran.
Imatinib-induced purpuric vasculitis. Ann Dermatol Venereol 2003; M Covadonga Martinez-Gonzalez
17. Clark SH, Duvic M, Prieto VG. Mycosis fungoides–like reaction in a pa-
tient treated with Gleevec. J Cutan Pathol 2003;30:279-81. Erratum
2004;31:81. OBJECTIF: Rapporter 3 cas de rash cutané de type livédoïde pouvant être
18. Gambacorti-Passerini C, Tornaghi L, Cavagnini F, et al. Gynaecomastia associés au traitement à l’imatinib.
in men with chronic myeloid leukaemia after imatinib. Lancet 2003;361: RÉSUMÉ: Cas 1: Un homme de 74 ans avec leucémie myéloïde chronique
1954-6. (chromosome de Philadelphie positif, LMC-Ph+), traité avec imatinib
19. Van de Voorde K, De Raeve H, Van Regenmortel N, Lambert J. Imatinib- 400 mg/jour a présenté un rash cutané de type livédoïde. Suite à
induced eccrine squamous syringometaplasia. J Am Acad Dermatol 2006; l’administration systémique de corticostéroïdes, une amélioration des
55:S58-9. lésions cutanées a été notée. Cas 2: Un homme de 66 ans avec LMC-
20. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the prob-
Ph+ a reçu un traitement d’imatinib 600 mg/jour. Après avoir débuté
l’imatinib, il a lui aussi présenté un rash cutané de type livédoïde.
ability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.
L’imatinib a alors été cessé et un traitement de corticostéroïdes topiques
a été débuté, permettant la résolution complète des lésions cutanées.
L’imatinib a été repris progressivement et les lésions ont réapparu. Le
patient est décédé en mai 2003 suite à la progression de sa maladie. Cas
EXTRACTO 3: Un homme de 43 ans avec leucémie lymphoblastique aiguë et Ph+ a
reçu de l’imatinib 600 mg/jour. En quelques jours, le patient a présenté
OBJETIVO: Presentar 3 casos de rash cutáneo con un aspecto livedoide un rash cutané de type livédoïde. Le patient est décédé possiblement
peculiar que podría estar asociado a la terapia con imatinib. d’un choc septique.
CASOS CLÍNICOS: Caso 1: Varón de 74 años con leucemia mieloide DISCUSSION: L’imatinib est un inhibiteur du récepteur de la tyrosine
crónica (CML) cromosoma Philadelphia positiva (Ph+), tratado con kinase qui inhibe la tyrosine kinase BCR/ABL. Plusieurs articles ont été
imatinib 400 mg/día, que desarrolló una erupción cutánea con patrón publiés sur les effets indésirables cutanés associés à l’imatinib. L’effet
livedoide. Se comenzó tratamiento con corticoides sistémicos con indésirable cutané le plus fréquent avec l’imatinib est le rash. Les
mejoría de las lesiones cutáneas. Caso 2: Varón de 66 años con CML auteurs du présent article rapportent 3 cas de rash cutanés de type
Ph+ que fue tratado con imatinib 600 mg/día. Tras el inicio de este livédoïde. L’évaluation du lien de causalité avec l’algorithme de Naranjo
tratamiento, presentó un rash cutáneo de patrón livedoide. El fármaco indique que les 3 réactions rapportées sont probablement reliées au
fue retirado y posteriormente reintroducido. Se inició tratamiento con traitement à l’imatinib.
corticoides tópicos, con remisión total de las lesiones cutáneas. Cuando
CONCLUSIONS: Bien que les réactions cutanées associées à l’imatinib
la dosis de imatinib fue reintroducida progresivamente, las lesiones
cutáneas recurrieron. El paciente falleció en mayo de 2003 debido a la soient fréquentes, elles sont fortement en lien avec la dose utilisée,
progresión de su enfermedad. Caso 3: Varón de 43 años con leucemia habituellement auto-limitantes ou facilement contrôlées par l’utilisation
aguda linfoblástica (ALL) Ph+ que fue tratado con imatinib 600 mg/día. d’une dose initiale plus faible d’imatinib et si nécessaire par
Tras unos pocos días desarrolló un rash cutáneo de patrón livedoide. El l’administration à court terme d’un corticostéroïde systémique.
paciente falleció como resultado de un probable shock séptico. Néanmoins, une attention particulière doit être portée lorsqu’un rash
DISCUSIÓN: El imatinib es un inhibidor del receptor de la tirosina kinasa,
que inhibe la tirosina kinasa BCR/ABL. Existen muchas publicaciones Alain Marcotte
sobre los efectos cutáneos adversos relacionados con este fármaco. El
152 I The Annals of Pharmacotherapy I 2007 January, Volume 41 www.theannals.com