Medical Journal of Babylon-Vol. 10- No. 3 -2013 مجلة بابل الطبية- المجلد العاشر- العدد s1

Medical Journal of Babylon-Vol. 10 - No. 3 -201 3 ةةةة ةةةة ةةةةةة- ةةةةةة ةةةةةة- ةةةةة ةةةةةة- 3 201

Received 1 April 2013 Accepted 20 May 2013 Abstract Imatinib mesylate (gleevec ) is a drug that used to treat certain cancers. Sixty – two patients with CMLs and GLSTs received gleevec capsules as a chemotherapeutic treatment were studied.. These patients developed one of the following cutaneous diseases mainly as an adverse cutaneous reaction to gleevec therapy for malignant diseases or as an association with it. Melasma ( 19.3% ), Eczema or dermatitis ( 14.5%), Acne – form rash (12.9%), Folliculitis (9.7%), Erythema nodosum (6.4%), Erythema multiforme (4.8%), Pruritus ( 4.8%), Pityriasis rosea( 3.2%), Psoriasis ( 3.2%), Chronic urticaria ( 3.2%), Xerosis of skin (3.2%), Vitiligo( 1.6%), Beau's lines of nails (1.6%), Cheilitis (1.6%), Common warts (1.6%), Herpes zoster (1.6%), Tinea incognito (1.6%),Lichenification (1.6%), Prurigo simplex (1.6%) and Palmar keratoderma (1.6%).From this study, gleevec was reported for the first time to cause or trigger the following adverse effects: seborrheic dermatitis , acne – form rash, classical erythema multiforme, atypical pityriasis rosea ( pityriasis circinate et marginate of widale) and acquired ichthyosis. Also this work, was the first one showed the association between gleevec and induction of erythema nodosum in Iraq. Gleevec was one of the considerable causes of .melasma in Iraq Key words: Glecvec , Adverse effects, Chronic myeloid leukemia, Gastro intestinal .stromal tumor الخلصة التأثيرات الجانبية المحتملة لعقار اليماتنيب ( الكليفيك ) المستخدم في علج مرضى سرطان الدم وأورام الجهاز الهضمي في مدينة الحلة . تم دراسة 62 حالة من مرضى سرطان الدم وأورام الجهاز الهضمي المتعاطين لعقار الكليفيك والمحالين من مركز الورام في مستشفى مرجان التعليمي إلى قسم المراض الجلدية والتناسلية في نفس المستشفى حيث كانوا يعانون من أمراض جلدية متنوعة ناتجة كتأثيرات جانبية لهذا العقار. تراوحت أعمار المرضى ما بين 21 – 72 سنة وكان عدد الذكور 38 (61.3% ) وعدد الناث 24 ( %38.7 ). كان عدد المصابين بسرطان الدم 48 (77.4%) واورام الجهاز الهضمي 14 (22.6%). تراوحت فترة العلج بعقار الكليفيك ما بين 2 شهر – 4 سنوات وجرعة العقار تراوحت ما بين 400 – 800 ملغم في اليوم. أثبتت الدراسة عن حصول بعض العراض الجانبية المؤثرة على الجلد نتيجة أخذ عقار الكليفيك ولول مرة حيث لم تثبت مسبقا في دراسات سابقة وهي كالتي: التهاب البشرة الدهني ، الطفح الشبيه بحب الشباب ، الحمرارية المتعددة الشكال التقليدية ، النخالية الوردية ، داء السمكة المكتسب، وكذلك

أثبتت الدراسة عن ارتباط عقار الكليفيك بالصابة بالحمرارية قالعقديةة ولول مرة في العراق ، ويعتبر العقار سبب مهم في الصابة بمرض الكلف في العراق. كذلك أثبتت الدراسة ارتباط العقار بأمراض جلدية أخرى كالتهاب بصيلت الشعر، الحكة ، الصدفية ، جفاف الجلد ، وكذلك تقرن باطن الكف أو القدم.

1 Medical Journal of Babylon-Vol. 10 - No. 3 -201 3 ةةةة ةةةة ةةةةةة- ةةةةةة ةةةةةة- ةةةةة ةةةةةة- 3 201

clinical efficacy in the treatment of CML by inducing complete remission Introduction and deceased mortality of CML matinib is a 2-phenylaminopyr- patients [6]. The Food and Drug imidine derivative chemotherapy Administration (FDA) has approved medication that belongs to a imatinib as first line treatment for group of medications, known as Philadelphia chromosome positive tyrosine kinase inhibitors [1]. TheseI CML both in adults and children, are a new kind of treatment known as " including after stem cell transplant targeted therapy " that is different from cases, in blast crisis and newly traditional therapy [2]. Most .[diagnosed [2 chemotherapy medications work by Imatinib is also used to treat killing rapidly dividing cells in the gastrointestinal stromal tumor ( GIST) body. Tyrosin kinase inhibitors prevent which is a type of tumor that grows in tumors from growing by reducing the the walls of digestive passages and action of proteins that control cell may spread to other parts of the division, growth and survival. These body[7]. Gain of function mutations of proteins are usually present in larger the KIT – receptor were found to be an quantities or more active in cancer early and pre – eminent oncogenic cells. By reducing the activity of these event in the vast majority of GISTs [8]. proteins, the growth and survival of This has led to therapy with imatinib .[cancer cells are reduced [1,2 mesylate, a highly selective inhibitor of Imatinib is marketed by the protein tyrosin kinase family Novartis as Gleevec ( USA) or Glivec comprising ABL, Chimeric BCR – (Europe / Australia / Latin America ) ABL, platelet derived growth factor as it's mesylate salt [2]. Gleevec has (PDGF) receptors α and β and the been shown to lower the number of product of C – KIT proto – oncogene white blood cells circulating (KIT ) [9]. The FDA first granted throughout the body [3]. In addition, it approval for advanced GIST patients blocks the growth of white blood cells in 2002. On February 2012, Imatinib that carry an abnormal protein linked was approved for use after the surgical to chronic myeloid leukemia(CML)[3]. removal of KIT – positive tumors to Chronic myeloid leukemia is a help prevent recurrence [10].The drug myeloproliferative disorder involving is also approved in unresectable KIT – the clonal expression of transformed .[positive GISTs [2 hematopoietic progenitor cells [4]. It is Gleevec is also used to treat characterized by a reciprocal dermato fibrosarcoma protuberance ( a translocation between the long arms of tumor that forms under the top layer of chromosomes 9 and 22 which generate skin), aggressive systemic the Philadelphia chromosome (ph) [4]. mastocytosis (a rare disorder caused by This leads to formation of the Bcr – too many mast cells in various tissues Abl oncogene which encodes the Bcr of the body), myelodysplastic/ – Abl protein, leading to constitutive myeloproliferative disease and activation of the Abl tyrosinase kinase hypereosinophilic syndrome / chronic [5]. Imatinib mesylate, the first eosinophilic leukemia [11]. Gleevec is selective tyrosinase kinase inhibitor being studied for the treatment of other targeting Bcr – Abl protein has shown tumors of blood based cancers

2 Medical Journal of Babylon-Vol. 10 - No. 3 -201 3 ةةةة ةةةة ةةةةةة- ةةةةةة ةةةةةة- ةةةةة ةةةةةة- 3 201 including melanoma, brain tumors, lung cancer, ovarian cancer, stomach Aim of the Study cancer and certain types of leukemia Imatinib mesylate (gleevec) is .[(Acute lymphoblastic leukemia)[11 commoncly used chemotherapy for The prescribed dose of imatinib treatment of CMLs and GISTs in slould be administered orally with a oncology unite in Merjan Teaching meal and a large glass of water. Doses Hospital. Several cases were referred of 400 mg or 600 mg should be to dermatology department for various administered once daily, where as a side effects or associated dose of 800 mg should be administered dermatological diseases during .[as 400mg twice a day[11 treatment period, so the aim of this The most common side effects of work was to shed light on these imatinib include weight gain, reduced adverse effects of gleevec therapy in number of blood cells (anemia, .Iraqi patients at Hilla city neutropenia, thrombocytopenia, headache, odema especially of the Patients and Methods lower legs and area around the eyes, Sixty – two patients with CMLs easy bruising and bleeding, fast and and GISTs who taking gleevec as a pounding heart beat, extreme tiredness, chemotherapeutic treatment for them nausea, vomiting, abdominal pain, were studied. These patients referred yellowish eyes and skin and from oncology unite in Merjan musculoskeletal pain [12]. Sever Teaching Hospital to the department of congestive cardiac failure is an dermatology during the period form uncommon but recognized side effect April 2010 to December 2012 for of imatinib and mice treated with large various cutaneous lesions and adverse doses, show toxic damage to their cutaneous reactions that patients myocardium [13]. If imatinib is used in complained when gleevec was prepubescent children, it can delay .prescribed for them normal growth, although a proportion A full history from each patient will experience catch – up growth was recorded including age, sex , type during, puberty[14]. Gleevec should of malignancy whether CML or GIST, not be taken or closely monitored when duration of CML or GIST, duration of there are certain medical problems gleevec treatment, dose of the drug and including liver disease, congestive duration of adverse cutaneous reactions heart failure, receiving chemotherapy, or skin problems that patients suffered kidney disease and a history of from it. Family history was also asked bleeding or a stomach ulcer. Pregnant about regarding CML or GIST or the women should not take gleevec and .skin complaint of patients .[neither breast feeding women[15 A thorough physical Dermatological side effects of examination was conducted to imatinib include: pruritic diagnose the type of cutaneous reaction maculopapular exanthem , follicular and the affected site of the body mucinosis, erythroderma , graft versus whether face, trunk or extremeties. host – like disease, mycosis- fungoides Skin biopsies were taken from some - like reaction, small vessel vasculitis, patients to confirm the diagnosis and generalized exanthematous pustulosis, sent for histopatholgical examination Sweet syndrome, erythema .by hemotoxyline and eosine staining multiforme, skin oedema, pigmentary changes and a lichenoid eruption [16, Results .[17 ,18

3 Medical Journal of Babylon-Vol. 10 - No. 3 -201 3 ةةةة ةةةة ةةةةةة- ةةةةةة ةةةةةة- ةةةةة ةةةةةة- 3 201 A total of 62 patients were ( mean  SD 2.7  2.7 years ). The enrolled in the study. Their ages duration of gleevec treatment ranged ranged from 20 years – 80 years (mean from 2 months to 4 years ( mean  SD,  SD, 45.4 ,  13.3 years ). There were .(2.5  2.5 years 38 males ( 61.3%) and 24 females All the patients had negative (38.7%). There were 48 patients with family history regarding CMLs or CMLs ( 77.4% ) and 14 patients with GISTs, or the cutaneous complaint GISTs ( 22.6% ). All these patients except one male patient with CML were treated with gleevec capsules ,the when one of his brothers had also dose ranged from 400 mg – 800 mg / . CML . ( day ( 4 – 8 capsules / day These patients developed one The period that these patients of the following cutaneous diseases had CMLs or GISTs since the time of mainly as an adverse cutaneous diagnosis ranged from 3 months in a reaction to gleevec chemotherapy for female patient with CML to 6 years in their malignant disease or as an another female patient with CML .(association with it ( table I

. Table I Adverse cutaneous reactions for gleevec therapy (% ) No. of cases Cutaneous Adverse effect (12 (19.3 Melasma -1 ( 9 (14.5 Eczema ( Dermatitis) -2 (8 (12.9 Acne – form rash -3 (6 (9.7 Folliculitis -4 ( 4 (6.4 Erythema nodosum -5 ( 3 (4.8 Erythema multiforme -6 (3 (4.8 Pruritus -7 (2 (3.2 Pityriasis rosea -8 (2 (3.2 Psoriasis -9 (2 (3.2 Chronic urticaria-10 (2 (3.2 Xerosis of skin-11 (1 (1.6 Vitiligo -12 ( 1 (1.6 Beau's lines of nails-13 (1 (1.6 Cheilitis-14 (1 (1.6 Common warts-15 (1 (1.6 Herpes zoster-16 (1 (1.6 Tinea incognito-17 (1 (1.6 Lichenification-18 (1 (1.6 Prurigo simplex-19 ( 1 (1.6 Palmar keratoderma-20

Melasma was seen in 12 months – 3 years ( mean  SD, 1.4  patients (19.3% ). There were 8 1.1 year). It followed gleevec intake females and 4 males, 10 patients with period from 5 months – 4 years ( mean CMLs and 2 patients with GISTs. .( SD , 3  2.4 years Melasma was presented as a brown Eczema was seen in 9 patients hyperpigmented patches affecting (14.5%). Four patients presented with cheeks, nose, fore head and upper lip, chronic eczema as plaques with some with butterfly distribution. The fissuring and exfoliation on the dorsum duration of melasma ranged from 2 of hands and Feet; 3 patients were with

4 Medical Journal of Babylon-Vol. 10 - No. 3 -201 3 ةةةة ةةةة ةةةةةة- ةةةةةة ةةةةةة- ةةةةة ةةةةةة- 3 201 discoid eczema with well demarcated Erythema multiforme with plaques on the extensor surfaces of the multiple papules and target like lesions hands, forearms and right lower leg, on the dorsum of both hands and face associated with itching. Seborrheic was seen in 3 patients (4.8%). The .dermatitis was found in 2 patients duration ranged from 2 – 4 weeks Acne – from rash was seen in ( mean  SD , 3.3  1.2 weeks). It 8 patients ( 12.9%). Clinically, it was followed a gleevec treatment period of either monomorphic in the form of about 6 months – 1 year ( mean  SD, either multiple papules or pustules or .(10  3.5 months dimorphic in the form of many papules Pruritus was seen in 3 patients and pustuls affecting the face, chest (4.8%). Two of them localized in the and upper back at the same time. No forearms, dorsum of the hands and the comedones were seen within the rash. back, one patient with generalized The duration of acne - form rash .pruritus all over the body ranged from 1 month – 1 year ( mean  Pityriasis rosea developed in 2 SD , 3  3months ). It followed a patients (3.2%). One female patient treatment period with gleevec from 4 with GIST had a classical presentation months – 2 years ( mean  SD, 1.1  of pityriasis rosea on the chest, back .( 0.8 year and upper arms with herald patch of 2 Folliculitis in a form of months duration following a treatment multiple boils involving the face, back period for gleevec of about 3 months. of the neck, lower abdomen and Another female patient with CML, had extremities was seen in 6 patients a pattern of pityriasis rosea called: (9.7%). The duration ranged from 1 – 3 pityriasis circinate et marginate of months. It followed a gleevec widal in which multiple annular treatment period ranged from 6 patches with collarrete scales on both months – 2 years. Two patients had thighs of 6 months duration following recurrent attack of folliculitis before 6 a treatment period for gleevec of about .months .9 months Erythema nodosum developed in 4 Psoriasis was found in 2 male patients ( 6 .4 %), 3 females and 1 patients with GISTs (3.2%). One male, 2 patients with CMLs and 2 patient presented with localized patients with GISTs. It presented as keratoderma on the right palm with painful and tender erythematous fissuring and other lesions of psoriasis nodules on both legs, some on the on the back and extremeties of 2 thighs and forearms. The duration months duration following gleevec ranged from 3 weeks – 2 months intake period of about 6 months. The (mean  SD, 4.7  2.2 weeks ). It other patient had psoriasis of scalp of 9 followed a treatment episode for months duration following a treatment gleevec ranged from 3 – 6 months .period of 1 year (mean  SD, 4.5  1.7 months ). A Chronic urticaria was seen in 2 biopsy was done for these patients and patients ( 3.2%). They had daily the result revealed septal panniculitis attacks of wheals all over the body for with a lymphohistiocytic infiltrate 3 – 6 months following 1 – 2 years extends from an interlobular septum .treatment period with gleevec into a fat lobule in a lace like fashion. Xerosis or dryness of the skin was seen One patient with CML had a similar in 2 patients( 3.2%). One of them had attack before 3 months, so developed fish – like scales on the forearms and .recurrent attack of erythema nodosum extensor surfaces of the legs with

5 Medical Journal of Babylon-Vol. 10 - No. 3 -201 3 ةةةة ةةةة ةةةةةة- ةةةةةة ةةةةةة- ةةةةة ةةةةةة- 3 201 ichthyosis – vulgaris – like picture skin repigmentation of vitiligo lesion .which is a type of acquired ichthyosis [25], imatinib – induced nail Vitiligo with depigmented patches on pigmentation [26] and imatinib – the cheeks and forearms appeared .[induced dental pigmentation [27 after 5 months treatment period of Although hypopigmentation of skin gleevec, Beau's lines of some fingers has been recognized as a frequent and and toes nails in a female patient with predictable effect of imatinib, only 1 GIST following gleevec treatment of patient with vitiligo had been reported about one and half year, cheilitis, in our study. It is currently not known common warts on both hands, thoracic how imatinib can induce both loss of herpes zoster, tinea incognito, pigment and darkening of skin in lichenification: thick skin with different patients. Changes in hyperpigmentation of dorsum of left cutaneous photosensitivity consisting foot, prurigo simplex: pruritic in both hypo – and hyperpigmentation excoriated papules on the abdomen and have been observed with imatinib and extremeties following 6 months have been attributed to an interference treatment period of gleevec and palmar with the molecular pathway involved keratoderma: yellowish thickening of in the response to ultraviolet stress skin on the left palm since the use of [18]. The persistent hyperpigmentation the drug. All of these cutaneous may be due to increased basal melanin findings were found in one patient for pigment, dermal melanin pigment .(each (1.6% incontinence and chronic Discussion inflammation. Imatinib causes diffuse Gleevec is a very powerful over stimulation of melanogenesis in medication, so side effects can be the skin[24]. How the same drug can expected to occur [19]. In patients produce both hypopigmentation and treated with imatinib, 7 – 21 % suffer darkening in the skin is unclear, but a adverse cutaneous reactions [20]. This possible explanation may reside in it's incidence appears to be dose – binding to different receptors in the dependent and 5% of such reactions skin, some with activator and other are sever or life – threatening [ 20]. with inhibitory effects on Imatinib can be reintroduced when it is melanogenesis [24]. Another possible associated to systemic steroids over a explanation for skin hypopigmentation short term, even in patients with severe is c – kit expression in melanocytes .[adverse cutaneous reaction [21 [23]. It plays a role in melanogenesis Melasma was the commonest and pigmentation that is a target for adverse cutaneous manifeststation seen .[imatinib [28 According to " e Health Me", Chloasma – like skin . (19.3%) Real world drug out comes, hyperpigmentation was reported as a personalized [29]: on Jan, 21 , 2013 : side effect in one patient with CML in 1, 302 people reported to have side Iranian study [22]. Other causes of effects when taking imatinib mesylate, melasma were excluded like iatrogenic among them, 3 patients ( 0.23%) have for example oral contraceptive pills in eczema(atopic dermatitis), 2 males and female patients or endocrine problems. 1 female and the age more than 60 No case of hyperpigmentation of the years. The time on imatinib when trunk or extremeties was seen in our patients have eczema was 1 – 6 patients, although it was reported in months. In our study, 9 patients had other studies [23,24]. There are case eczema (14.5 %), 7 females and 2 reports regarding imatinib – induced males with the age ranged from 31

6 Medical Journal of Babylon-Vol. 10 - No. 3 -201 3 ةةةة ةةةة ةةةةةة- ةةةةةة ةةةةةة- ةةةةة ةةةةةة- 3 201 years to 67 years ( mean  SD ; 53  the drugs that induces acne – form 12.4 years ), and the time on imatinib .eruption when patients had eczema was 4 Boil folliculitis was seen in 6 months – 2 years. The differences patients (9.7%). Cases of diabetes and between the high number of eczema in Behcet's disease were excluded in our our patients compared to what patients. This percentage of folliculitis reported in the literature because 7 of was apparently more common than our eczema patients had chronic what recorded about gleevec – irritant contact dermatitis or discoid induced folliculitis according to " e eczema may be due to other causes of Health Me", Real world outcome contact with irritants or chemicals and [29]7:On detergents especially more common Jan 13, 2013 : 19: 806 people reported in females and some may have eczema to have side effects when taking even before taking gleevec as a gleevec, among then 9 patients (0.05 treatment, but in 2 patients, 31 years %) have folliculitis and the time on old male and 47 years old female, gleevec was 6 – 12 months. The developed seborrheic dermatitis for discrepancy between the results was the first time 4 – 6 months after related to relatively less number of our gleevec intake and in sever form studied patients according to " e Health involving the face, chest and scalp, and Me " drug out come and to the time of one of them get good control of study period " 2 years " compared to " seborrheic dermatitis after stopping the 11 years " of " e Health Me " in which treatment for a short time. So, we can the side effects were general systemic conclude that imatinib could be one of and dermatological. In our patients , triggering drugs for induction of only cutaneous side effects were seborrheic dermatitis which was not studied. This discrepancy between the reported previousely. No patient in the results was also noticed in other side .study had atopic dermatitis effects when compared with" e Health Acne – form rash was the next Me " world drug outcome, for the same common side effect of imatinib seen in .reasons 8 patients ( 12.9%). It was seen for the Erythema nodosum ( EN) was first time when the patient started to found in 4 patients ( 6.4%). Other take gleevec for 4 months – 2 years. cause of EN were excluded like The majority of the patients were infection for example: streptococcal young adults 23 – 40 years. There was infection, autoimmune disorders like no history of ingestion of drugs that inflammatory bowel disease or induce acne like systemic steroids or Behcet's disease, pregnancy in female using potent topical steroids on the patients and medications for example: face or chest for any reason. Behest's oral contraceptive pills and disease was excluded in our patients as sulfonamides. According to " e Health acne – form rash is one of it's Me" drug outcome : on Jan 21, 2013 : cutaneous manifestations. No case of from 19, 806 people reported to have imatinib – induce acne was reported in side effects when taking gleevec, 19 the literature except one case of patients (0.10%) have EN. The time on hyperigmented acne rosacea during gleevec when these patients have EN gleevec treatment for GIST [30]. So, was less than 1 month in 20% and this high number of acne patients for from 6 – 12 months in 80%. Our the first time after gleevec intake may patients developed EN when the lead to consider that imatinib is one of treatment period of gleevec was 3 – 6 months. To the best of our knowledge,

7 Medical Journal of Babylon-Vol. 10 - No. 3 -201 3 ةةةة ةةةة ةةةةةة- ةةةةةة ةةةةةة- ةةةةة ةةةةةة- 3 201 this work was the first registration that were also reported [31,32]. According imatinib mesylate is one of the drugs to " e Health Me " drug outcome: On which cause erythema nodosum in Iraq Jan 8, 2013 : 19, 806 people reported and middle east and it should be to have side effects when taking considered beside other drugs like gleevec, among them 5 patients sulfonamides and oral contraceptives ( 0.03%) have PR. All reported cases because there are many patients with of PR were classical or with typical CML in Iraq in which gleevec is the presentation, but in our study, a case of .drug of first choice in their treatment atypical PR was reported ( pityriasis Erythema multiforme ( E.M ) was circinate et marginate of widal ) which other side effect of gleevec therapy lasts for a longer time than the occurred in 3 patients (4.8%) following classical PR and located mainly on a treatment period of about 6 months – .both thighs 1 year. We should ask about herpes Psoriasis was seen in 2 patients simplex infection which is the ( 3.2%). According to " e Health Me commonest cause or trigger for E.M in " drug outcome: On Jan 18 , 2013 : 19, Iraq. According to " e Health Me " 806 people reported to have side drug outcome: Steven - Johnson effects when they were on gleevec , 31 syndrome which is a severe form of patients (0.16%) have psoriasis. E.M , with erosions, blisters and Psoriasis vulgaris was also reported to disseminated cutaneous eruption, was be exacerbated by imatinib therapy reported in 2 patients from 1,305 [33]. The exacerbation of psoriasis was patients had side effects when taking likely due to the increase in Th 1 cells imatinib, when the time on the drug .[associated with imatinib therapy [33 was less than 1 month. In the literature According to " e Health Me " drug there was no case report about E.M outcome; on Jan 25, 2013 : 1,302 with it's classical presentation of people reported to have side effects macular or papular lesions with iris or when taking imatinib, among them one target lesions (E.M minor) as what male patient aged 55 years (0.08 %) presented in our study, but what had urticaria in 2006. In our study, reported was only the severe form only 2 male patients ( 3.2%) had .( ( Steven – Johnson's syndrome chronic urticaria aged 50 and 60 years According to " e Health Me " with 3 -6 months duration following 1 drug outcome ; pruritus reported in 16 .– 2 years treatment period of gleevec patients (1.23%) from 1,305 people Xerosis or dryness of skin was had side effects when taking gleevec found in 2 patients(3.2%). In " e and the time on imatinib when patients Health Me " drug outcome; on Jan 26, have prunitus was less than 1 month in 2013 : 21, 449 people who reported to 50% and from 1 – 6 months in have side effects when taking imatinib, 50%.Females an males were equally only 2 patients had xerosis of skin affected. In our study, 3 patients (0.12%). In our study, one of the developed pruritus ( 4.8%), 2 females patients had ichthyosis – vulgaris like and 1 male, when they were on gleevec picture, so gleevec could be one of the from 6 months – 1 year. Other causes drugs that may cause acquired of pruritus were excluded whether ichthyosis which was not reported in .dermatological or systemic .the literature Pityriasis rosea ( PR) was seen in 2 Beau's lines of some fingers patients (3.2%). In the literature, and toes nails with palmar keratoderma several cases of pityriasis rosea – like were seen in one patient for each since drug eruption induced by imatinib the use of gleevec for treatment(1.6%).

8 Medical Journal of Babylon-Vol. 10 - No. 3 -201 3 ةةةة ةةةة ةةةةةة- ةةةةةة ةةةةةة- ةةةةة ةةةةةة- 3 201 No case report declared such perspective. J Clin Investing. 2007; association with imatinib therapy. The .117: 2033 – 5 rest of cutaneous manifestations like Madhusudan S, Ganesan TS. Tyrosine-6 cheilitis, hespes zosters, prurigo kinase inhibitors in cancer therapy. simplex, lichenification, common .Clin Biochem. 2004 ; 37: 618 – 35 warts and tinea incognito were seen in Druker BJ, Kinase Tamura S,-7 1 patient for each (1.6%). They may be Buchdunger E. effects of a selective associated accidently with the use of inhibitor of the Abl tyrosine kinase on .gleevec therapy for CML patients the growth of Bcr – Abl positive cells. .Nat Med. 1996; 2(5): 561 – 6 Buchdunger E, Cioffi CL , Law N. Abl-8 Conclusions protein – tyrosine kinase inhibitor Gleevec was one of the considerable-1 STI571 inhibits invitro signal .causes of melasma in Iraq transduction mediated by C – Kit and From this study, gleevec was reported-2 platelet derived growth factor receptor for the first time to cause or trigger the J pharmacol Exp Ther. 2000 ; following adverse effects: seborrheic .295[1] : 139 – 45 dermatitis, acne – form rash, classical Heinrich MC, Griffith DJ, Druker BJ.-9 erythema multiforme, atypical Inhibition of C – Kit receptor tyrosine pityriasis rosea ( pityriasis circinate et kinase inhibitor. Blood. 2000; 96(3): marginate of widale), acquired .925 – 32 .ichthyosis and Beau's lines of nails Prolonged use of imatinib in GIST"-10 This work, was the first report showed-3 ."patients leads to new FDA approval the association between gleevec and Guilhot F. Indications for imatinib-11 induction of erythema nodosum in Iraq mesylate therapy and clinical mesylate. .and middle east .Oncologist. 2004; 9: 271 – 81 Gleevec should be consider as a cause-4 Schwab C. Advances in the-12 or trigger for folliculitis, pruritus, management of chronic myeloid psoriasis, xerosis of skin and palmo leukemia with Abl Kinase inhibitors. .plantar keratoderma .Oncology Briefings. 2006; 41 – 3 Kerkela R, Grazette L , Yacobi R,-13 References Cardiotoxicity of the cancer Takimoto CH, Calvo E. principles of-1 therapeutic agent imatinib mesylate. oncologic pharmacotherapy. In : .Nat. Med. 2006 ; 12(8) : 908 – 16 Pazdur R, Wagman LD, Camphor Shima H, Tokuyama M, Tanizawa A.-14 Usen KA, Hoskins WJ, eds. Cancer Distinct impact of Imatinib on growth Management: A multidisciplinary at prepubertal and pubertal ages of .Approach. 11th ed. 2008 : 2437 – 48 children with chronic myeloid abc " FDA high lights and prescribing-2 leukemia. J. pediatr. 2011; (159) : 676 informations for Gleevec [ Imatinib .– 81 .(mesylate Tsao AS, Kantarjian H, Cortes J,-15 Deininger MW, Druker BJ. Specific-3 Obrien S, Talpaz M. Imatinib mesylat targeted therapy of chronic causes hypopigmentation in the skin. myelogenous leukemia with Imatinib. . Cancer. 2003; 98: 2483 – 7 .Pharmacol. Rev. 2003; 55(3):401-23 Ayrirookuzhi SJ, MaL, Ramshesh P,-16 Faderl S,Talpaz M, Estrov Z. The-4 Mills G. Imatinib – induced sweet biology of chronic myeloid leukemia. syndrome in a patient with chronic .N Engl J Med. 199 9; 341: 164 – 72 myeloid leukemia. Arch Dermatol. Nowell PC. Discovery of the-5 .2005; 14:368 – 70 Philadelphia chromosome: a personal

9 Medical Journal of Babylon-Vol. 10 - No. 3 -201 3 ةةةة ةةةة ةةةةةة- ةةةةةة ةةةةةة- ةةةةة ةةةةةة- 3 201 Pascual JC, Matarredona J, Miralles J,-17 patient with recurrent GIST. JAAD. Conesa V, Borras – Blasco J. Oral and .2008; 59(5) : 580 – 3 cutaneous lichened reaction secondary Prabhast K, Biswas Gh, Prasad N,-26 to imatinib: report of two cases. Int J Koran N, Sastry PS, parikh PM. .Dermatol. 2006 ; 45 : 1471 – 3 Imatinib – induced nail pigmentation Robert C, Soria JC, Spatz A, Lecesne-18 in CML. Indian J Dermatol Venereol A, Malka D, pautier P. cutaneous side . leprol. 2006; 72 (1): 63 – 4 effects of kinase inhibitors and Singh N, Bakhshi S. Imatinib –-27 blocking antibodies. Lancet Oncol. induced dental hyperpigmentation in .2005; 29: 208 – 9 childhood CML. J pediatr Hematol Uptodate 17.3 , 2009 . Drug-19 .Oncol. 2007; 29(3) : 208 – 9 .information : Imatinib Tsao AS, Kantarjian H, Cortes J,-28 Brouard MV, Saurat JH. Cutaneous-20 OBrienS, Talpaz M. imatinib mesylate reactions to ST1S 71. N Eng J Med. causes hypopigmentation in the skin. .2001; 345:618 – 9 .Cancer. 2003; 98: 2483 – 7 Blanca SG, Jose C , pascual R, Isabel-21 e Health Me "; Real World drug " -29 BR, Concepcion R , Gloria VA. Sever outcomes, personalized. Dermatology skin reaction to imatinib in a case of .Online Journal Philadelphia – positive acute Umut D, Ugur C, Ozlem E, Banu O, I-30 lymphoblastic leukemia blood. 2003; sailay BY, Mustafa B, Suleyman B. .101 : 2446 Acne rosacea associated imatinib Valizadeh N. Imatinib – induced facial-22 mesylate in GIST patient. J Oncol skin hyperpigmentation in a case of . Pharm pract. 2011; 17(3) : 285 – 7 chronic mycloid leukemia. Shiraz E. Cho AY, Kim DH, Im M, LeeY, Seo-31 .Medical Journal. 2011 ; 12(3):3 YJ, Lee JH. Pityriasis rosea – like Arora B, Kumar L, Sharma A,-23 drug eruption induced by imatinib Wadhwa J, Kochupillai V. pigmentary mesylate. Ann Dermatol 2011;23:S360 changes in chronic myeloid leukemia .– 3 patients treated with imatinib mesylate. Brazzelli V, prestinari F , Roveda E,-32 .Ann Oncol. 2004; 15: 358 – 9 Barbagallo T, Bellani E, Vassallo C. Alexandrescu DT, Dasanu CA,-24 PR – like eruption during treatment Farzanmehr H, Kauffan CL. Persistent with imatinib mesylate: description of cutaneous hyperpigmentation after 3 cases. J Am Acad Dermatol. 2005 ; tyrosine kinase inhibition with imatinib .53 ( S suppl 1 ) : S 240 – 3 for GIST. Dermatology Online Shimizu K, Kuroda H, Kida M,-33 .Journal. 2008; 14(7):7 Watanabe H, Shirao S, Akiyama T. Hui H, yang – yang Y, YU – houng W.-25 psoriasis vulgaris exacerbated by Imatinib mesylate induced Imatinib therapy in CML. Rinsho repigmentation of vitiligo lesion in a .Ketsueki. 2005; 46( 10): 1152 – 5