Clinical Review & Education

JAMA Clinical Challenge

Scalp Pustules in a Patient Receiving Chemotherapy

Hsien-Yi Chiu, MD; Hsien-Ching Chiu, MD

Figure 1.

An 85-year-old man with lung cancer (stage IV, adenocarcinoma) was

treated with the epidermal growth factor receptor [EGFR] inhibitor gefitinib (250 mg/d). One month later, he developed a few erythematous follicular papules with focal scaling on the scalp, which intermittently improved and worsened and were reasonably well controlled with
topical corticosteroids. Neither pustules nor hair loss was noted. The
cancer was well controlled for 31 months, when his tumor recurred and
he was switched to erlotinib (150 mg/d). Subsequently, the number of
scalp lesions increased, accompanied by pustules and hair loss. Numerous pustules with an erythematous
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base were observed on the scalp vertex
(Figure 1). Paronychia, pruritus, and dry skin
were also present, but the pustular eruption was limited to the scalp.
Neither fever nor other constitutional symptoms were noted. Testing
of the scalp lesions using a potassium hydroxide (KOH) preparation produced negative results.

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WHAT WOULD YOU DO NEXT?

A. Do nothing; the rash usually resolves

over time
B. Obtain a bacterial culture from the pustules
C. Obtain a Tzanck smear from the pustules
D. Obtain a skin biopsy from the pustules

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JAMA Clinical Challenge Clinical Review & Education

Diagnosis
EGFRinduced acneiform eruption

What to Do Next
D. Obtain a skin biopsy from the pustules
The key clinical feature is the consideration of EGFR inhibitor
induced acneiform eruption when evaluating papulopustular scalp
lesions in cancer patients treated with EGFR inhibitors.

Discussion
EGFR inhibitors are increasingly used to treat advanced malignancy.
However, the adverse effects of some EGFR inhibitors diminish quality 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 cause distinctive cutaneous adverse
effectsincludingacneiformeruptions,paronychia,trichomegaly,brittle
and curly hairs, xerosis, and mucositis.1 Studies among EGFR inhibitor knockout mice showed thinning of skin and poorly defined stratification of the epidermis and altered terminal differentiation of the
epidermis and hair follicles.2 EGFR inhibitorinduced skin toxicities can
be paradoxically helpful because they reflect response to tumor
treatment,3 but studies have found a dissociation between the efficacy of gefitinib and early skin toxicity.4-6 A recent study demonstrated that the relationship between EGFR inhibitorinduced acneiform eruption and tumor response might decrease over time.1
Fifty percent to 70% of patients treated with EGFR inhibitors develop acneiform eruptions or papulopustular rashes.7 Because EGFR
mediates hair growth cycles and the inflammatory process, its inhibition seems to cause acneiform eruption resulting from abnormal keratinization, follicular retention and rupture, and subsequent failure
to ameliorate inflammation.2 The hair is usually not affected, but reports exist of hair texture changes, including fine, brittle, and curly
hair.8 Transgenic mice expressing inactive mutant EGFR in skin and
hairfollicleshaveshort,wavyhairandwhiskercurling.9 Extensivescalp
acneiform eruption, as was seen in this patient, can occur.8,9
EGFRinduced acneiform eruption can present with hair loss
with numerous scalp pustules resembling scalp infections, particularly tinea capitis. The differential diagnosis of scalp pustules in-

cludes dissecting cellulitis, folliculitis decalvans, fungal

infections, erosive pustular dermatosis, and acute localized exanthematous pustulosis. To determine which of these entities
is present, a skin biopsy is obtained after KOH testing and obtaining fungal cultures to evaluate for tinea capitis. Erlotinib was
not discontinued in this patient. EGFR inhibition likely
caused the skin lesions, because pustules first appeared afFigure 2. Skin biopsy from the scalp
ter the initiation of erlotinib; rerevealing diffuse inflammatory cell
sults of fungal and bacterial
infiltration around hair follicles and in
testing were negative, as was
the dermis, consisting of predominant
the response to antifungal
lymphoplasmacytic cells and focal
drugs; and the skin biopsy findneutrophils (hematoxylin-eosin,
original magnification 40).
ings were consistent with EGFR
inhibitorinduced acneiform
eruption. Topical and oral antibiotics and corticosteroids may be used
to treat EGFR inhibitorinduced acneiform eruption. Topical recombinant human epidermal growth factor may also be effective.10

Patient Outcome
Initially, despite the negative KOH fungal preparation, the scalp rash
was diagnosed as tinea capitis. The treatment response to oral and
topical antifungal agents was poor. A skin biopsy showed a dense
perifollicular, perivascular, and interstitial infiltrate consisting of predominant lymphoplasmacytic cells and focal neutrophils (Figure 2).
Periodic acidSchiff staining did not reveal spores or hyphae. Repeated fungal and bacterial cultures were negative, as were responses to KOH testing of the hairs and pustules. The skin lesion significantly improved with 1 month of doxycycline. However, the
patient continued to have episodic flares of scalp pustules approximately 2 to 3 times a year.

ARTICLE INFORMATION

REFERENCES

Author Affiliations: Department of Dermatology,

National Taiwan University Hospital Hsin-Chu
Branch, Hsin-Chu, Taiwan (H.-Y. Chiu); Department
of Dermatology, National Taiwan University
Hospital, Taipei, Taiwan (H.-C. Chiu).

1. Osio A, Mateus C, Soria JC, et al. Cutaneous

side-effects in patients on long-term treatment
with epidermal growth factor receptor inhibitors.
Br J Dermatol. 2009;161(3):515-521.

Corresponding Author: Hsien-Ching Chiu, MD,

Department of Dermatology, National Taiwan
University Hospital, 7 Chung-Shan South Rd, Taipei
100, Taiwan (hcchiu1003@ntu.edu.tw).
Section Editor: Huan J. Chang, MD, Associate Editor.
Conflict of Interest Disclosures: The authors have
completed and submitted the ICMJE Form for
Disclosure of Potential Conflicts of Interest and
none were reported.
Submissions: We encourage authors to submit
papers for consideration as a JAMA Clinical
Challenge. Please contact Dr Chang at tina.chang
@jamanetwork.org.

2. Lacouture ME. Mechanisms of cutaneous

toxicities to EGFR inhibitors. Nat Rev Cancer.
2006;6(10):803-812.
3. Peuvrel L, Bachmeyer C, Reguiai Z, et al.
Semiology of skin toxicity associated with
epidermal growth factor receptor (EGFR) inhibitors.
Support Care Cancer. 2012;20(5):909-921.
4. Kris MG, Natale RB, Herbst RS, et al. Efficacy of
gefitinib, an inhibitor of the epidermal growth
factor receptor tyrosine kinase, in symptomatic
patients with nonsmall cell lung cancer: a
randomized trial. JAMA. 2003;290(16):2149-2158.
5. Fukuoka M, Yano S, Giaccone G, et al. Multiinstitutional randomized phase II trial of gefitinib for
previously treated patients with advanced non
small-cell lung cancer (the IDEAL 1 Trial) [corrected].
J Clin Oncol. 2003;21(12):2237-2246.

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6. Giovannini M, Gregorc V, Belli C, et al. Clinical

significance of skin toxicity due to EGFR-targeted
therapies [published online June 22, 2009].
J Oncol. doi:10.1155/2009/849051.
7. Robert C, Soria JC, Spatz A, et al. Cutaneous
side-effects of kinase inhibitors and blocking
antibodies. Lancet Oncol. 2005;6(7):491-500.
8. Graves JE, Jones BF, Lind AC, Heffernan MP.
Nonscarring inflammatory alopecia associated with
the epidermal growth factor receptor inhibitor
gefitinib. J Am Acad Dermatol. 2006;55(2):
349-353.
9. Costa DB, Kobayashi S, Schumer ST.
Erlotinib-associated alopecia in a lung cancer
patient. J Thorac Oncol. 2007;2(12):1136-1138.
10. Shin JU, Park JH, Cho BC, Lee JH. Treatment of
epidermal growth factor receptor inhibitorinduced
acneiform eruption with topical recombinant
human epidermal growth factor. Dermatology.
2012;225(2):135-140.

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