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sone in our commentary.1
We did not mention the
potential adverse effect of ACD to topical
hydrocortisone because it did not play a role in the
debate regarding the appropriate ness of
permitting OTC sale of topical hydrocortisone
prepa rations.
As pointed out by Watsky and Warshaw, the
ready availability of OTC hydrocortisone products
(especially in structural class A) likely contributes to
a high prevalence of clinically significant positive
patch test results to corti costeroid markers in
selected patch-tested populations. How this
translates to the prevalence of corticosteroid
induced ACD in the population at large is
apparently not known. At what level
corticosteroid-induced ACD might be a public
health concern requiring consideration of remov ing
products from the market is not only an intriguing
question but one that could, depending on the
answer, re sult—following the law of unintended
consequences—in proving correct, after all, the
initial reaction of the derma tology community.
William H. Eaglstein, MD
Scott M. Ravis
Correspondence: Dr Eaglstein, Research and
Develop ment, Stiefel Laboratories Inc, 255
Alhambra Cir, Coral Gables, FL 33134
(weaglstein@stiefel.com).
1. Ravis SM, Eaglstein WH. Topical hydrocortisone from prescription to
over the-counter sale. Arch Dermatol. 2007;143(3):413-415.
VIGNETTES
Successful Treatment of Pityriasis Versicolor With
5-Aminolevulinic Acid
Photodynamic Therapy
Pityriasis versicolor is a common chronic
super ficial fungal infection caused by the organism
Mal
assezia furfur. Although many conventional
treat ments have been shown to be successful in
treating pityriasis versicolor, therapy of long-term
duration may be needed in many cases, and
recurrence is not uncom mon. In vitro experimental
investigations have demon strated that several
fungal strains can be effectively in activated by
irradiation with visible light wavelengths in the
presence of photosensitizer.1-3
However, to our
knowl edge, there have been no clinical trials of
photodynamic therapy (PDT) against pityriasis
versicolor.
Report of a Case. A 37-year-old man presented
with a 2-year history of asymptomatic, light brown,
scaly patches on both axillae (Figure 1A).
Microscopic examination of samples stained with
10% potassium hydroxide re vealed short, thick,
fungal hyphae and spores of various sizes (Figure
2A). We tried to treat the lesions with
A B
Figure 1. A 37-year-old man with a 2-year history of scaly patches on both axillae. A, Sharply marginated, light brown hyperpigmentation with
fine scales on the axilla. B, Clearance of pityriasis versicolor without reinfection after 16 weeks of follow-up after treatment with
5-aminolevulinic acid in combination with photodynamic therapy.
(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 9), SEP 2007 WWW.ARCHDERMATOL.COM
1218
©2007 American Medical Association. All rights reserved.
Downloaded From: http://archderm.jamanetwork.com/ by a Nanyang Technological University User on 05/22/2015
A B
Figure 2. Microscopic examination of samples stained with 10% potassium hydroxide (original magnification 400 for both panels). A,
Before treatment, numerous short, thick fungal hyphae and spores of various sizes are seen. B, No fungal hyphae or spores are present
10 weeks after the last treatment.
5-aminolevulinic acid (ALA) in combination with
PDT. Topical 20% ALA (Medac, Hamburg,
Germany) in pet rolatum vehicle was applied to the
lesions and covered with an occlusive
polyurethane film (Tegaderm; 3M, St Paul,
Minnesota). After 4 hours, excess ALA was re
moved, and the lesions were irradiated with light
from light-emitting diodes (mean±SD wavelength,
630±50 nm). The light intensity was 100 mW/cm2
,
and the light doses were 70 J/cm2
for the left axilla
and 80 J/cm2
for the right axilla. The procedure was
repeated 2 weeks later with increased light dose
increments of 10 J/cm2
on each side. The area
cleared within 4 weeks, and the patient was
observed for an additional 3 months without rein
fection (Figure 1B). One week after the first
treatment and 10 weeks after the last treatment,
samples stained with 10% potassium hydroxide
were again taken from both axillae and these
smears showed no fungal hyphae or spores
(Figure 2B). Of note, the clearance was maintained
throughout the warm and humid summer of Korea.
Comment. To our knowledge, only 1 clinical trial of
PDT treatment for mycotic infection has been
reported.4
In that study, interdigital mycosis of the
feet was irradiated with 75 J/cm2
. The clearance
was seen in 6 of 9 patients after 1 (n=4) or 4 (n=2)
treatments. However, 4 patients re ported
recurrences 4 weeks after the last treatment. The
authors suggested that in vivo environmental condi
tions such as temperature, humidity, and pH of the
in terdigital skin could induce a poor cell uptake of
ALA and a deficient biosynthesis of protoporphyrin
IX. In ad dition, the irregular tridimensional shape
of this pecu liar anatomic area could lead to a
nonuniform delivery
of light and/or ALA cream. The better outcome in
our case with a similar light dose may be due to the
different causative fungal strain and relatively
uniform delivery of light and ALA cream to the
affected sites.
In the treatment of pityriasis versicolor, standard
drug treatments are prolonged, and the
appearance of drug resistant strains is becoming
more frequent. The multi plicity of cellular targets in
fungi should reduce the risk of selection of
photomutant, resistant strains after PDT, and this
risk should be further minimized by the lack of
mutagenic effects of PDT.5
Our results of prompt
clear ance and no recurrence of pityriasis versicolor
after PDT indicate that this approach may be a
promising treat ment for pityriasis versicolor.
Young Jin Kim, MD
You Chan Kim, MD, PhD
Correspondence: Dr Y. C. Kim, Department of
Derma tology, Ajou University School of Medicine,
5 Wonchon Dong, Yeongtong-Gu, Suwon 443-721,
South Korea (maychan@ajou.ac.kr).
Financial Disclosure: None reported.
1. Wainwright M. Photodynamic antimicrobial chemotherapy (PACT). J
Anti microb Chemother. 1998;42(1):13-28.
2. Strakhovskaya MG, Shumarina AO, Fraikin GY, Rubin AB. Synthesis
of pro toporphyrin IX induced by 5-aminolevulinic acid in yeast cells in
the pres ence of 2,2;-dipyridyl. Biochemistry (Mosc).
1998;63(6):725-728.
3. Smijs TG, van der Haas RN, Lugtenburg J, Liu Y, de Jong RL,
Schuitmaker HJ. Photodynamic treatment of the dermatophyte
Trichophyton rubrum and its microconidia with porphyrin
photosensitizers. Photochem Photobiol. 2004; 80(2):197-202.
4. Calzavara-Pinton PG, Venturini M, Capezzera R, Sala R, Zane C.
Photody namic therapy of interdigital mycoses of the feet with topical
application of 5-aminolevulinic acid. Photodermatol Photoimmunol
Photomed. 2004;20(3): 144-147.
(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 9), SEP 2007 WWW.ARCHDERMATOL.COM
1219
©2007 American Medical Association. All rights reserved.
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5. Calzavara-Pinton PG, Venturini M, Sala R. A comprehensive overview
of pho todynamic therapy in the treatment of superficial fungal
infections of the skin. J Photochem Photobiol B. 2005;78(1):1-6.
Leukemia Cutis: A Presenting Sign in
Acute Promyelocytic Leukemia
Report of a Case. A 63-year-old woman
developed 3 ery thematous, pruritic plaques on her
left lower extremity. She called her dermatologist
and was prescribed pred nisone for likely contact
dermatitis from poison ivy. Two weeks later, the
patient developed fatigue and bruising. Findings
from a complete blood cell count were abnor mal,
demonstrating blasts (promyelocytes predomi
nant), anemia, and thrombocytopenia. The patient
was admitted for workup.
On admission, her white blood cell count was
4500 cells/µL (normal range, 4500-11 000
cells/µL); hemato crit level was 31.4% (normal
range, 35%-45%); and plate let count was 33
103
/µL (normal range, 153 103
/µL to 367 103
/µL). A
manual differential count demon strated 62%
promyelocytes. Analysis of bone marrow bi opsy
specimens showed markedly hypercellular mar row
with 90% promyelocytes and a positive
translocation of 15:17 on fluorescence in situ
hybridization. Flow cy tometry revealed cells
positive for CD13, CD33, CD38, and CD117 and
negative for CD14, CD64, CD2, CD11, CD3, CD20,
CD7, CD34, and HLA-DR, which was con sistent
with acute promyelocytic anemia. Polymerase
chain reaction revealed a 0.436 ratio of the
PML-RAR-α onco gene in her bone marrow.
A dermatology consultant was called to evaluate
3 ery thematous, nontender, indurated plaques with
necrotic centers on her left calf, ranging in size
from 5 to 9 mm (Figure 1). Scattered petechiae and
ecchymoses were present. The differential
diagnosis included vasculitis, leu kemia cutis,
arthropod assault, panniculitis, deep fun gal
infection, and atypical mycobacteria. Tissue cul
tures were negative for bacteria, fungal elements,
and mycobacteria. Histopathologic analysis
revealed, pan dermally and in the subcutaneous
fat, dense, perivascu lar, and interstitial infiltrate of
malignant, immature, granulocytic cells with
extensive tissue hemorrhage. These tumor cells
contained polymorphic nuclei with abun dant
granular cytoplasm. Occasional mitotic figures
were present. The immature hematopoietic cells
stained dif fusely positive for chloracetic esterase
by Leder stain and were CD34 negative. A few
immature cells contained eo sinophilic, cytoplasmic
granules. No epidermotropism or vascular or
neural invasion was noted (Figure 2). The findings
confirmed the diagnosis of leukemia cutis, and the
morphologic features were consistent with promy
elocytic leukemia.
The patient underwent a chemotherapeutic
regimen of daunorubicin and all-trans retinoic acid
(ATRA) fol lowed by cytarabine, daunorubicin, and
arsenic triox ide. Four months after her initial
presentation, a bone marrow biopsy specimen
showed no abnormalities, and her disease is
currently in remission. The leukemia cu tis lesions
on her calf are well healed.
Figure 1. Three erythematous, nontender, indurated plaques with
necrotic centers ranging in size from 5 to 9 mm were present on the
patient’s left calf.
Figure 2. In a biopsy specimen taken from a lesion on the
patient’s calf, immature hematopoietic cells stained diffusely
positive for chloracetic esterase by Leder stain (original
magnification 40).
Comment. Leukemia cutis is the dissemination of
sys temic leukemia and a poor prognostic sign. It
presents as papules, plaques, or nodules, with a
characteristic vio laceous color.
Diffuse infiltration of leukemic cells into the
dermis, subcutis, blood vessels, and skin adnexa
are seen on his tologic examination.1
Immunohistochemical study char acterizes the
immunophenotypes of leukemic cells.
Acute promyelocytic leukemia (APL), classified
as AML-M3 (acute myeloid leukemia, subtype M3)
in the French-American-British classification
system, ac counts for approximately 10% to 15% of
acute myeloid leukemia in adults.2
Patients may
have abundant abnor mal progranulocytes, severe
coagulopathy, and a bal anced reciprocal
translocation, t(15;17)(q22;q12), in leu kemic cells.3
Fusion of the promyelocytic leukemia gene (PML)
on chromosome 15 and the retinoic acid recep tor
(RAR- ) on chromosome 17 to form the oncogene
PML-RAR- occurs.2
At 5 years, 70% to 80% of
patients with APL are disease free with treatment,
which in cludes ATRA and anthracycline-based
chemotherapy.2
(REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 9), SEP 2007 WWW.ARCHDERMATOL.COM
1220
©2007 American Medical Association. All rights reserved.
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Successful treatment of pityriasis versicolor with 5-aminolevulinic acid photodynamic therapy

  • 1. sone in our commentary.1 We did not mention the potential adverse effect of ACD to topical hydrocortisone because it did not play a role in the debate regarding the appropriate ness of permitting OTC sale of topical hydrocortisone prepa rations. As pointed out by Watsky and Warshaw, the ready availability of OTC hydrocortisone products (especially in structural class A) likely contributes to a high prevalence of clinically significant positive patch test results to corti costeroid markers in selected patch-tested populations. How this translates to the prevalence of corticosteroid induced ACD in the population at large is apparently not known. At what level corticosteroid-induced ACD might be a public health concern requiring consideration of remov ing products from the market is not only an intriguing question but one that could, depending on the answer, re sult—following the law of unintended consequences—in proving correct, after all, the initial reaction of the derma tology community. William H. Eaglstein, MD Scott M. Ravis Correspondence: Dr Eaglstein, Research and Develop ment, Stiefel Laboratories Inc, 255 Alhambra Cir, Coral Gables, FL 33134 (weaglstein@stiefel.com). 1. Ravis SM, Eaglstein WH. Topical hydrocortisone from prescription to over the-counter sale. Arch Dermatol. 2007;143(3):413-415. VIGNETTES Successful Treatment of Pityriasis Versicolor With 5-Aminolevulinic Acid Photodynamic Therapy Pityriasis versicolor is a common chronic super ficial fungal infection caused by the organism Mal assezia furfur. Although many conventional treat ments have been shown to be successful in treating pityriasis versicolor, therapy of long-term duration may be needed in many cases, and recurrence is not uncom mon. In vitro experimental investigations have demon strated that several fungal strains can be effectively in activated by irradiation with visible light wavelengths in the presence of photosensitizer.1-3 However, to our knowl edge, there have been no clinical trials of photodynamic therapy (PDT) against pityriasis versicolor. Report of a Case. A 37-year-old man presented with a 2-year history of asymptomatic, light brown, scaly patches on both axillae (Figure 1A). Microscopic examination of samples stained with 10% potassium hydroxide re vealed short, thick, fungal hyphae and spores of various sizes (Figure 2A). We tried to treat the lesions with
  • 2. A B Figure 1. A 37-year-old man with a 2-year history of scaly patches on both axillae. A, Sharply marginated, light brown hyperpigmentation with fine scales on the axilla. B, Clearance of pityriasis versicolor without reinfection after 16 weeks of follow-up after treatment with 5-aminolevulinic acid in combination with photodynamic therapy. (REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 9), SEP 2007 WWW.ARCHDERMATOL.COM 1218 ©2007 American Medical Association. All rights reserved. Downloaded From: http://archderm.jamanetwork.com/ by a Nanyang Technological University User on 05/22/2015 A B Figure 2. Microscopic examination of samples stained with 10% potassium hydroxide (original magnification 400 for both panels). A, Before treatment, numerous short, thick fungal hyphae and spores of various sizes are seen. B, No fungal hyphae or spores are present
  • 3. 10 weeks after the last treatment. 5-aminolevulinic acid (ALA) in combination with PDT. Topical 20% ALA (Medac, Hamburg, Germany) in pet rolatum vehicle was applied to the lesions and covered with an occlusive polyurethane film (Tegaderm; 3M, St Paul, Minnesota). After 4 hours, excess ALA was re moved, and the lesions were irradiated with light from light-emitting diodes (mean±SD wavelength, 630±50 nm). The light intensity was 100 mW/cm2 , and the light doses were 70 J/cm2 for the left axilla and 80 J/cm2 for the right axilla. The procedure was repeated 2 weeks later with increased light dose increments of 10 J/cm2 on each side. The area cleared within 4 weeks, and the patient was observed for an additional 3 months without rein fection (Figure 1B). One week after the first treatment and 10 weeks after the last treatment, samples stained with 10% potassium hydroxide were again taken from both axillae and these smears showed no fungal hyphae or spores (Figure 2B). Of note, the clearance was maintained throughout the warm and humid summer of Korea. Comment. To our knowledge, only 1 clinical trial of PDT treatment for mycotic infection has been reported.4 In that study, interdigital mycosis of the feet was irradiated with 75 J/cm2 . The clearance was seen in 6 of 9 patients after 1 (n=4) or 4 (n=2) treatments. However, 4 patients re ported recurrences 4 weeks after the last treatment. The authors suggested that in vivo environmental condi tions such as temperature, humidity, and pH of the in terdigital skin could induce a poor cell uptake of ALA and a deficient biosynthesis of protoporphyrin IX. In ad dition, the irregular tridimensional shape of this pecu liar anatomic area could lead to a nonuniform delivery of light and/or ALA cream. The better outcome in our case with a similar light dose may be due to the different causative fungal strain and relatively uniform delivery of light and ALA cream to the affected sites. In the treatment of pityriasis versicolor, standard drug treatments are prolonged, and the appearance of drug resistant strains is becoming more frequent. The multi plicity of cellular targets in fungi should reduce the risk of selection of photomutant, resistant strains after PDT, and this risk should be further minimized by the lack of mutagenic effects of PDT.5 Our results of prompt clear ance and no recurrence of pityriasis versicolor after PDT indicate that this approach may be a promising treat ment for pityriasis versicolor. Young Jin Kim, MD You Chan Kim, MD, PhD Correspondence: Dr Y. C. Kim, Department of Derma tology, Ajou University School of Medicine, 5 Wonchon Dong, Yeongtong-Gu, Suwon 443-721, South Korea (maychan@ajou.ac.kr). Financial Disclosure: None reported. 1. Wainwright M. Photodynamic antimicrobial chemotherapy (PACT). J Anti microb Chemother. 1998;42(1):13-28. 2. Strakhovskaya MG, Shumarina AO, Fraikin GY, Rubin AB. Synthesis of pro toporphyrin IX induced by 5-aminolevulinic acid in yeast cells in the pres ence of 2,2;-dipyridyl. Biochemistry (Mosc). 1998;63(6):725-728. 3. Smijs TG, van der Haas RN, Lugtenburg J, Liu Y, de Jong RL, Schuitmaker HJ. Photodynamic treatment of the dermatophyte Trichophyton rubrum and its microconidia with porphyrin photosensitizers. Photochem Photobiol. 2004; 80(2):197-202. 4. Calzavara-Pinton PG, Venturini M, Capezzera R, Sala R, Zane C. Photody namic therapy of interdigital mycoses of the feet with topical application of 5-aminolevulinic acid. Photodermatol Photoimmunol Photomed. 2004;20(3): 144-147. (REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 9), SEP 2007 WWW.ARCHDERMATOL.COM 1219 ©2007 American Medical Association. All rights reserved. Downloaded From: http://archderm.jamanetwork.com/ by a Nanyang Technological University User on 05/22/2015 5. Calzavara-Pinton PG, Venturini M, Sala R. A comprehensive overview of pho todynamic therapy in the treatment of superficial fungal infections of the skin. J Photochem Photobiol B. 2005;78(1):1-6. Leukemia Cutis: A Presenting Sign in Acute Promyelocytic Leukemia Report of a Case. A 63-year-old woman developed 3 ery thematous, pruritic plaques on her left lower extremity. She called her dermatologist and was prescribed pred nisone for likely contact dermatitis from poison ivy. Two weeks later, the patient developed fatigue and bruising. Findings from a complete blood cell count were abnor mal, demonstrating blasts (promyelocytes predomi nant), anemia, and thrombocytopenia. The patient was admitted for workup. On admission, her white blood cell count was 4500 cells/µL (normal range, 4500-11 000 cells/µL); hemato crit level was 31.4% (normal range, 35%-45%); and plate let count was 33 103 /µL (normal range, 153 103 /µL to 367 103 /µL). A manual differential count demon strated 62% promyelocytes. Analysis of bone marrow bi opsy specimens showed markedly hypercellular mar row with 90% promyelocytes and a positive translocation of 15:17 on fluorescence in situ hybridization. Flow cy tometry revealed cells positive for CD13, CD33, CD38, and CD117 and negative for CD14, CD64, CD2, CD11, CD3, CD20, CD7, CD34, and HLA-DR, which was con sistent with acute promyelocytic anemia. Polymerase chain reaction revealed a 0.436 ratio of the PML-RAR-α onco gene in her bone marrow. A dermatology consultant was called to evaluate
  • 4. 3 ery thematous, nontender, indurated plaques with necrotic centers on her left calf, ranging in size from 5 to 9 mm (Figure 1). Scattered petechiae and ecchymoses were present. The differential diagnosis included vasculitis, leu kemia cutis, arthropod assault, panniculitis, deep fun gal infection, and atypical mycobacteria. Tissue cul tures were negative for bacteria, fungal elements, and mycobacteria. Histopathologic analysis revealed, pan dermally and in the subcutaneous fat, dense, perivascu lar, and interstitial infiltrate of malignant, immature, granulocytic cells with extensive tissue hemorrhage. These tumor cells contained polymorphic nuclei with abun dant granular cytoplasm. Occasional mitotic figures were present. The immature hematopoietic cells stained dif fusely positive for chloracetic esterase by Leder stain and were CD34 negative. A few immature cells contained eo sinophilic, cytoplasmic granules. No epidermotropism or vascular or neural invasion was noted (Figure 2). The findings confirmed the diagnosis of leukemia cutis, and the morphologic features were consistent with promy elocytic leukemia. The patient underwent a chemotherapeutic regimen of daunorubicin and all-trans retinoic acid (ATRA) fol lowed by cytarabine, daunorubicin, and arsenic triox ide. Four months after her initial presentation, a bone marrow biopsy specimen showed no abnormalities, and her disease is currently in remission. The leukemia cu tis lesions on her calf are well healed. Figure 1. Three erythematous, nontender, indurated plaques with necrotic centers ranging in size from 5 to 9 mm were present on the patient’s left calf. Figure 2. In a biopsy specimen taken from a lesion on the patient’s calf, immature hematopoietic cells stained diffusely positive for chloracetic esterase by Leder stain (original magnification 40). Comment. Leukemia cutis is the dissemination of sys temic leukemia and a poor prognostic sign. It presents as papules, plaques, or nodules, with a characteristic vio laceous color. Diffuse infiltration of leukemic cells into the dermis, subcutis, blood vessels, and skin adnexa are seen on his tologic examination.1 Immunohistochemical study char acterizes the immunophenotypes of leukemic cells. Acute promyelocytic leukemia (APL), classified as AML-M3 (acute myeloid leukemia, subtype M3) in the French-American-British classification system, ac counts for approximately 10% to 15% of acute myeloid leukemia in adults.2 Patients may have abundant abnor mal progranulocytes, severe coagulopathy, and a bal anced reciprocal translocation, t(15;17)(q22;q12), in leu kemic cells.3 Fusion of the promyelocytic leukemia gene (PML) on chromosome 15 and the retinoic acid recep tor (RAR- ) on chromosome 17 to form the oncogene PML-RAR- occurs.2 At 5 years, 70% to 80% of patients with APL are disease free with treatment, which in cludes ATRA and anthracycline-based chemotherapy.2 (REPRINTED) ARCH DERMATOL/ VOL 143 (NO. 9), SEP 2007 WWW.ARCHDERMATOL.COM 1220 ©2007 American Medical Association. All rights reserved. Downloaded From: http://archderm.jamanetwork.com/ by a Nanyang Technological University User on 05/22/2015