correspondence

n engl j med 366;5 nejm.org february 2, 2012

481

sion spectrum was 330 to 450 nm (peak, 390 to

410) at 10 minutes and at 24 hours after irradia-

tion in five patients during vemurafenib treat-

ment. None of the patients had a history of photo-

sensitive diseases.

The minimal erythema dose of UVB was nor-

mal (range, 0.008 to 0.099 J per square centime-

ter) in all patients. The minimal erythema dose

of UVA (range, 10 to 49 J per square centimeter)

was already strikingly reduced in all patients after

10 minutes and after 24 hours (Fig. 1A). Three

patients reported a burning, painful sensation

during UVA exposure. The ultraviolet-irradiated

fields showed intense erythema associated with

pronounced edema (Fig. 1B).

In one patient, we performed minimal ery-

thema dose testing for UVA after the application

of a UVA-tailored sun-protection product (the UVB

filter was octocrylene, and the UVA filters were

ecamsule, drometrizole trisiloxane, avobenzone,

and titanium dioxide), resulting in a complete

normalization (Fig. 1C).

On the basis of the nature and the evolution

of the skin lesions, we conclude that vemurafenib

causes UVA-dependent phototoxicity. The UVA

dependency is also compatible with reports of

sunburns after ultraviolet exposure through glass

while driving a car. In contrast to UVB, UVA

penetrates glass.

5

This information and other

UVA-specific properties such as constant inten-

sity regardless of daylight and season should be

communicated to patients who are beginning to

receive therapy with vemurafenib. In our experi-

ence, broad-spectrum sunscreens were effective

in eliminating UVA-induced phototoxicity, and we

now routinely recommend the use of UVA-tailored

sunscreens and ultraviolet-dense clothing to

patients receiving vemurafenib.

5

An ultraviolet-

protection schedule that takes into account UVA-

dependent phototoxicity should largely prevent

vemurafenib photosensitivity.

Reinhard Dummer, M.D.
Jeannine Rinderknecht, M.D.
Simone M. Goldinger, M.D.

University Hospital Zurich
Zurich, Switzerland

Disclosure forms provided by the authors are available with

the full text of this letter at NEJM.org.

1.

Bollag G, Hirth P, Tsai J, et al. Clinical efficacy of a RAF in-

hibitor needs broad target blockade in BRAF-mutant melanoma.

Nature 2010;467:596-9.

2.

Flaherty KT, Puzanov I, Kim KB, et al. Inhibition of mutated,

activated BRAF in metastatic melanoma. N Engl J Med 2010;363:

809-19.

3.

Ribas A, Kim KB, Schuchter LM, et al. BRIM-2: an open-

label, multicenter phase II study of vemurafenib in previously

treated patients with BRAFV600E mutation-positive metastatic

melanoma. J Clin Oncol 2011;29:Suppl:8575. abstract.

4.

Chapman PB, Hauschild A, Robert C, et al. Improved sur-

vival with vemurafenib in melanoma with BRAF V600E muta-

tion. N Engl J Med 2011;364:2507-16.

5.

Fourtanier A, Moyal D, Seité S. Sunscreens containing the

broad-spectrum UVA absorber, Mexoryl SX, prevent the cutane-

ous detrimental effects of UV exposure: a review of clinical

study results. Photodermatol Photoimmunol Photomed 2008;24:

164-74.

Staphylococcus aureusReactivationOsteomyelitis

after75Years

To the Editor:

In 1934, a 10-year-old girl was

hospitalized at the Children’s Hospital of Boston

for 1 1/2 years for Staphylococcus aureus osteomyeli-

tis of the left femur. This was the preantibiotic

era, so she did not receive any antibiotic therapy

at that time but, instead, underwent multiple or-

thopedic procedures including “scalloping” (i.e.,

removal of infected bone). She recovered fully,

never underwent any drainage procedures, and

did well until she reached 85 years of age, when

she felt pain in her left midfemur while rising

from a chair. The following day she noted a pu-

rulent drainage from her left thigh and presented

to our institution.

Radiographic findings identified a pathologic

fracture of the left midfemur, scalloping changes,

and medullary changes consistent with osteomy-

elitis. After successful open reduction and inter-

nal fixation of the fracture, she recovered with-

out sequelae. During surgery, an old sinus tract

that had never drained was found. All cultures

of samples from the bone and tract grew only

S. aureus; there was no evidence of a malignant

condition. As expected, the S. aureus strain was

sensitive to all antibiotics tested, including pen-

icillin and oxacillin.

Sequence type 30 (ST30) S. aureus femoral os-

teomyelitis became reactivated in our patient

after 75 years. S. aureus reactivation osteomyelitis

occurring many decades after the initial infec-

The New England Journal of Medicine

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Copyright © 2012 Massachusetts Medical Society. All rights reserved.

n engl j med 366;5 nejm.org february 2, 2012

482

notices

tion has been reported previously.

1,2

We per-

formed Multi Locus Sequence Typing of the re-

covered S. aureus strain in standard fashion,

3

and

seven S. aureus housekeeping genes (arcC, aroE, glpF,

gmk_, pta_, tpi_, and yqiL) were fully sequenced

with the use of the Applied Biosystems 3730xl

DNA Analyzer. The allelic profile of this S. aureus

strain placed it among ST30 S. aureus isolates.

3

In the 1950s and 1960s, a penicillin-resistant

but methicillin-susceptible ST30 S. aureus clone

spread throughout the world.

4

More recently,

community-acquired and hospital-acquired meth-

icillin-susceptible and methicillin-resistant strains

of ST30 S. aureus have been reported to be the

prevalent clones in Australia and Oceania.

5

Our

report suggests that an ST30 S. aureus clone sen-

sitive to all antibiotics was circulating in the

eastern United States in 1934.

Daniel H. Libraty, M.D.
Chinmay Patkar, Ph.D.

University of Massachusetts Medical School
Worcester, MA
[e-mail]

Brenda Torres, B.S.

University of Massachusetts Memorial Healthcare
Worcester, MA

Supported by grants from the National Institute of Allergy and

Infectious Diseases (UO1AI065654 and R01AI091820).

Disclosure forms provided by the authors are available with

the full text of this letter at NEJM.org.

1.

Case Records of the Massachusetts General Hospital (Case

6-1993). N Engl J Med 1993;328:422-8.

2.

Al-Maiyah M, Hemmady MV, Shoaib A, Morgan-Jones RL.

Recurrence of chronic osteomyelitis in a regenerated fibula after

65 years. Orthopedics 2007;30:403-4.

3.

Multi Locus Sequence Typing home page. 2011 (http://saureus

.mlst.net).

4.

Deleo FR, Otto M, Kreiswirth BN, Chambers HF. Community-

associated methicillin-resistant Staphylococcus aureus. Lancet

2010;375:1557-68.

5.

Vandenesch F, Naimi T, Enright MC, et al. Community-

acquired methicillin-resistant Staphylococcus aureus carrying

Panton-Valentine leukocidin genes: worldwide emergence. Emerg

Infect Dis 2003;9:978-84.

Correspondence Copyright © 2012 Massachusetts Medical Society.

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ValVEs in ThE hEarT of ThE Big applE: EValuaTion

& ManagEMEnT of ValVular hEarT DisEasEs

The fourth annual scientific session of the Heart Valve Soci-

ety of America and the Society for Heart Valve Disease will be

held in New York, April 12–14. Deadline for early registration

is Feb. 24. Deadline for submission of abstracts is Feb. 14.

Contact the Heart Valve Society of America, P.O. Box 1365,

New York, NY 10012; or e-mail info@heartvalvesocietyofamerica

.org; or see http://www.heartvalveconference.com.

1sT annual sCiEnTifiC sYMposiuM on lung

hEalTh afTEr DEploYMEnT To iraQ & afghanisTan

The symposium will be held in Stony Brook, NY, on Feb. 13.

It is sponsored by the Stony Brook University School of Medi-

cine Office of CME.

Contact Dr. Anthony Szema, c/o Myra Intoci, Office of CME,

Stony Brook University School of Medicine, HSC Level 2,

Room 142, Stony Brook, NY 11794-8222; or call (631) 444-

2094; or e-mail [e-mail]; or see http://

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prinCiplEs of prEVEnTion in priMarY CarE:

pEarls anD piTfalls

The conference will be held in Boston, May 17–19.

Contact Harvard Medical School, Department of Continuing

Education, P.O. Box 825, Boston, MA 02117-0825; or call (617)

384-8600; or e-mail [e-mail]; or see http://

www.cme.hms.harvard.edu/courses/prevention.

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