DESCRIPTION
Kemoterapi dan SCALP pustulTRANSCRIPT
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Scalp Pustules in a Patient Receiving Chemotherapy
Hsien-Yi Chiu,MD; Hsien-Ching Chiu,MD
An85-year-oldmanwith lungcancer (stage IV, adenocarcinoma)was
treated with the epidermalgrowth factor receptor[EGFR] inhibitor ge-
fitinib (250 mg/d). One month later, he developed a few erythema-
tous follicular papules with focal scaling on the scalp, which intermit-tentlyimprovedandworsenedandwerereasonablywellcontrolledwith
topical corticosteroids. Neither pustules nor hair loss was noted. The
cancerwas well controlled for31 months, when histumor recurred and
he wasswitched to erlotinib (150 mg/d).Subsequently, the number of
scalp lesions increased, accompanied by pustules and hair loss. Nu-
merous pustules with an erythematous
base were observed on the scalp vertex
(Figure1).Paronychia,pruritus,anddryskin
were also present, but the pustular eruption was limited to the scalp.
Neither fever nor other constitutional symptoms were noted. Testing
ofthescalplesionsusingapotassiumhydroxide(KOH)preparationpro-
duced negative results.
Figure 1.
Quiz at jama.com
WHAT WOULDYOUDO NEXT?
A. Do nothing; the rash usually resolves
overtime
B. Obtainabacterialculturefromthepus-
tules
C. Obtain a Tzanck smear from the pus-
tules
D. Obtain a skin biopsy from the pus-
tules
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Diagnosis
EGFR–induced acneiform eruption
Whatto DoNext
D. Obtaina skin biopsyfrom thepustules
The keyclinicalfeature is theconsiderationof EGFR inhibitor–
induced acneiform eruption whenevaluating papulopustular scalp
lesions in cancer patients treated with EGFRinhibitors.
Discussion
EGFR inhibitors are increasinglyused to treat advanced malignancy.
However, theadverse effectsof someEGFR inhibitorsdiminishqual-
ity of life or result in dose modification or discontinuation of these
drugs. EGFR inhibitors, which play an important role in skin and hair
follicle metabolic signaling, can causedistinctive cutaneous adverse
effectsincludingacneiformeruptions,paronychia, trichomegaly, brittle
and curly hairs, xerosis, and mucositis.1 Studies among EGFR inhibi-
torknockoutmiceshowed thinningof skin andpoorly definedstrati-
fication of the epidermis and altered terminal differentiation of the
epidermisandhairfollicles. 2EGFRinhibitor–inducedskintoxicitiescan
be paradoxically helpful because they reflect response to tumor
treatment,3 but studieshave found a dissociation between the effi-
cacy of gefitinib and early skin toxicity.4-6 A recent study demon-
strated that the relationshipbetweenEGFR inhibitor–induced acne-
iform eruption and tumor response might decrease over time.1
Fiftypercentto70%ofpatientstreatedwithEGFRinhibitorsde-
velopacneiformeruptionsor papulopustular rashes.7Because EGFR
mediates hair growth cycles and the inflammatory process, its inhi-
bitionseemstocauseacneiformeruptionresultingfromabnormalke-
ratinization, follicular retention and rupture, and subsequent failure
to ameliorateinflammation.2 Thehair is usuallynot affected, butre-
ports exist of hair texture changes, including fine, brittle, and curly
hair.8 Transgenic mice expressing inactive mutant EGFR in skin and
hairfollicleshaveshort,wavyhairandwhiskercurling. 9Extensivescalp
acneiform eruption, as wasseen in this patient, canoccur.8,9
EGFR–induced acneiform eruption can present with hair losswithnumerousscalp pustules resemblingscalp infections, particu-
larly tinea capitis. The differential diagnosis of scalp pustules in-
cludes dissecting cellulitis, fol-
l i cul i t i s deca l v a n s , f un g a l
infections, erosivepustular der-
matosis,and acute localized ex-
anthematous pustulosis. To de-
termine which of these entities
is present, a skin biopsy is ob-
tainedafterKOHtestingandob-taining fungal cultures to evalu-
atefor tineacapitis. Erlotinib was
not discontinued in this pa-
tient. EGFR inhibition likely
caused the skin lesions, be-
causepustules firstappeared af-
ter the initiation of erlotinib;re-
sults of fungal and bacterial
testing were negative, as was
the response to antifungal
drugs; and the skin biopsyfind-
ingswere consistent withEGFR
inhibitor–induced acneiform
eruption.Topicaland oralantibioticsand corticosteroidsmaybe used
to treat EGFRinhibitor–inducedacneiform eruption.Topicalrecom-
binanthuman epidermalgrowth factor may also be effective.10
PatientOutcome
Initially, despitethe negativeKOHfungalpreparation, thescalprash
was diagnosed as tineacapitis. The treatmentresponseto oraland
topical antifungal agents was poor. A skin biopsy showed a dense
perifollicular, perivascular, andinterstitialinfiltrate consistingof pre-
dominantlymphoplasmacyticcells andfocal neutrophils (Figure2).
Periodic acid–Schiff staining did not reveal spores or hyphae. Re-
peated fungal and bacterial cultures were negative, as were re-
sponsestoKOHtestingofthehairsandpustules.Theskinlesionsig-
nificantly improved with 1 month of doxycycline. However, thepatient continuedto haveepisodicflares of scalp pustulesapproxi-
mately 2 to3 times a year.
ARTICLEINFORMATION
Author Affiliations: Departmentof Dermatology,
National TaiwanUniversityHospital Hsin-Chu
Branch, Hsin-Chu, Taiwan(H.-Y. Chiu);Department
of Dermatology, National TaiwanUniversity
Hospital, Taipei,Taiwan(H.-C. Chiu).
Corresponding Author: Hsien-Ching Chiu,MD,
Departmentof Dermatology, National Taiwan
UniversityHospital, 7 Chung-Shan SouthRd, Taipei
100, Taiwan ([email protected]).
Section Editor: HuanJ. Chang,MD, AssociateEditor.Conflict of Interest Disclosures: Theauthors have
completedand submittedtheICMJEForm for
Disclosure of Potential Conflicts of Interest and
nonewere reported.
Submissions: Weencourageauthors to submit
papers forconsideration as a JAMA Clinical
Challenge.Please contact Dr Changat tina.chang
@jamanetwork.org.
REFERENCES
1. Osio A, MateusC, Soria JC,et al.Cutaneous
side-effects in patients on long-termtreatment
withepidermal growthfactor receptor inhibitors.
BrJ Dermatol . 2009;161(3):515-521.
2. Lacouture ME. Mechanismsof cutaneous
toxicitiesto EGFRinhibitors.NatRev Cancer .
2006;6(10):803-812.
3. Peuvrel L, BachmeyerC, ReguiaiZ, etal.
Semiology of skintoxicity associatedwith
epidermal growthfactor receptor (EGFR) inhibitors. Support Care Cancer . 2012;20(5):909-921.
4. KrisMG, NataleRB, HerbstRS, etal. Efficacy of
gefitinib,an inhibitor of theepidermal growth
factorreceptortyrosine kinase, in symptomatic
patientswith non–smallcell lung cancer: a
randomized trial. JAMA. 2003;290(16):2149-2158.
5. Fukuoka M,YanoS, GiacconeG, etal. Multi-
institutionalrandomized phase II trial of gefitinibfor
previouslytreated patientswith advancednon–
small-cell lungcancer (the IDEAL 1 Trial)[corrected].
J ClinOncol . 2003;21(12):2237-2246.
6. Giovannini M, GregorcV,BelliC, etal. Clinical
significanceof skintoxicitydue to EGFR-targeted
therapies [published onlineJune 22, 2009].
J Oncol . doi:10.1155/2009/849051.
7. RobertC, Soria JC,SpatzA, et al.Cutaneous
side-effectsof kinaseinhibitors and blocking
antibodies. LancetOncol . 2005;6(7):491-500.
8. GravesJE, JonesBF, Lind AC,HeffernanMP.
Nonscarringinflammatoryalopecia associated with
the epidermal growthfactor receptor inhibitor
gefitinib. J AmAcadDermatol . 2006;55(2):
349-353.
9. CostaDB, KobayashiS, Schumer ST.
Erlotinib-associated alopecia in a lungcancer
patient. J ThoracOncol . 2007;2(12):1136-1138.
10. ShinJU,Park JH,Cho BC,Lee JH.Treatmentof
epidermal growthfactor receptor inhibitor–induced
acneiform eruption withtopical recombinant
humanepidermalgrowth factor. Dermatology .
2012;225(2):135-140.
Figure 2. Skin biopsyfrom thescalp
revealing diffuseinflammatory cell
infiltrationaround hair follicles and in
the dermis, consistingof predominant
lymphoplasmacyticcells and focal
neutrophils (hematoxylin-eosin,
original magnification×40).
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