Download Chondrodermatitis Nodularis Helicis Successfully

THE CUTTING EDGE
SECTION EDITOR: EDWARD W. COWEN, MD, MHSc;
ASSISTANT SECTION EDITORS: MURAD ALAM, MD; WILLIAM D. AUGHENBAUGH, MD
Chondrodermatitis Nodularis Helicis Successfully
Treated With Photodynamic Therapy
Yolanda Gilaberte, MD, PhD; Marı́a Pilar Frias; Juan Blas Pérez-Lorenz, MD, PhD; Departments of Dermatology
(Dr Gilaberte and Ms Frias) and Internal Medicine (Dr Pérez-Lorenz), Hospital San Jorge, Huesca, Spain;
and Aragon Health Sciences Institute, Zaragoza, Spain (Drs Gilaberte and Pérez-Lorenz and Ms Frias)
The Cutting Edge: Challenges in Medical and Surgical Therapeutics
Chondrodermatitis nodularis helicis (CDNH) is a painful inflammatory condition affecting the helix of the ear.
We describe 5 patients with CDNH who were successfully treated with methyl aminolevulinate photodynamic therapy (PDT).
sion 2 years previously. The mean duration of the CDNH
was 11.6 months (range,6-24 months).
REPORT OF CASES
Conservative techniques, such as pressure-relieving devices and topical and intralesional corticosteroids, are considered to be the first-line option and attain a cure rate
of 87% in 15 patients, albeit after a short follow-up period (mean duration of follow-up, 4.5 months).1 Perilesional collagen injection,2 laser excision,3 and cryosurgery have also been described with variable results.
Surgical methods include curettage and cautery,4 as well
as techniques for the removal of affected cartilage with
skin5,6 and without skin.7 The mean cure rate of these surgical techniques is 84.2% (range,69%-100%)6 with different cosmetic outcomes.
Five patients at our clinic, 3 women and 2 men, with a
mean age of 77 years (age range, 58-88 years), were diagnosed as having CDNH. All cases presented with 1 or
2 small, painful erythematous nodules, 3 of which were
centered by an ulcer, on the upper part of the helix
(Figure 1). Two patients also had a painful erythematous lesion on the antihelix. Pressure-relieving devices,
topical corticosteroids, and cryotherapy had been previously used with little or no improvement. In addition,
in 1 case the lesion was a recurrence after surgical exci-
THERAPEUTIC CHALLENGE
B
A
Figure 1. Chondrodermatitis nodularis helicis in a 76-year-old woman resistant to cryotherapy. A, Before. B, One month after 1 session of methyl
aminolevulinate–photodynamic therapy (Metvix for 3 hours following by irradiation with light-emitting diode light [Aktilite; PhotoCure ASA, Oslo, Norway]) at a
wavelength of 630 nm at 37 J/cm2.
(REPRINTED) ARCH DERMATOL/ VOL 146 (NO. 10), OCT 2010
1080
WWW.ARCHDERMATOL.COM
©2010 American Medical Association. All rights reserved.
Downloaded From: http://jamanetwork.com/ on 10/18/2016
SOLUTION
Lesionsweretreatedwithmethylaminolevulinate–PDT.They
were prepared by cleaning with alcohol and using a curette
to scrape away crusts, the keratotic plug, or the superficial
part of the more nodular lesions. Then methyl aminolevulinate, 16% (Metvix; Galderma, Sophia Antipolis, France),
was applied on and 1 cm around the lesions and under the
occlusive dressing (Tegaderm; 3M Healthcare, St Paul, Minnesota) and then covered with aluminum foil for 3 hours.
Fluorescence was detected using visible ultraviolet light at
405 nm, which showed a diffuse soft red fluorescence in the
lesional area (Figure 2). Subsequently, the treatment sites
wereirradiatedwithalight-emittingdiode(LED)lightsource
at a wavelength of 630 nm at 37 J/cm2 (Aktilite lamp; PhotoCure ASA, Oslo, Norway). The treatment was well tolerated, and neither notable pain nor adverse effects were
present during the irradiation or in the following days. All
lesions resolved with an excellent cosmetic outcome
(Figure 1), except for 1 patient whose disease did not completely respond after 3 treatments 1 month apart.
COMMENT
Chondrodermatitis nodularis helicis is a painful condition that is difficult to treat. Histologically, CDNH consists of a nodule of degenerate homogeneous collagen surrounded by vascular granulation tissue with an overlying
acanthotic epidermis, and there may be a central ulcer
through which the damaged collagen is extruded. In nearly
all cases there is inflammation and fibrosis of the underlying perichondrium, and degenerative changes may be
seen in the cartilage. Many authors view the condition
as an example of transepidermal elimination of altered
connective tissue.8 Pressure and a compromised local
blood supply are believed to be key factors in the development and recurrence of CDNH.9 Various theories regarding its etiology have been published about the initial event: that it is the result of (1) cartilaginous changes,
(2) hyperkeratosis leading to the perforation, (3) cold or
poor circulation, and/or (4) traumatic injury to the collagen.10 As to the efficacy of PDT for CDNH, it could act
on several pathogenic factors. Our hypothesis is based
on (1) its anti-inflammatory and immunomodulatory action, (2) its effect on vascularization or on collagen, and
(3) a possible chondroprotective effect. In skin areas
treated with aminolevulinic acid (ALA)-PDT, inflammatory reactions seem to slow down because of the resident macrophages and mast cells death and the slow recovery to cytokine responsiveness of the surviving cell
population.11 It is generally accepted that PDT causes acute
inflammation, but it is also thought that the judicious application of acute inflammation can interrupt the process of chronic inflammation and stimulate healing.12
Topically applied methyl aminolevulinate sensitizes
mainly keratinocytes; using protocols of irradiation, which
may induce sublethal cellular effects, several cytokines
are released by those cells, possibly resulting in a change
of cytokine equilibrium in the inflammatory milieu and
finally leading to a disruption of the chronic inflammation present in CDNH.13 In relation to the role of topical
Figure 2. Chondrodermatitis nodularis helicis on the helix: a moderate
fluorescence is present in the lesional area.
PDT on improving blood supply in CDNH, it has been
proved that blood perfusion is increased immediately after irradiation and persists up to a week.14 Regarding the
effect on collagen, no changes in synthesis of collagen
type II, the major connective tissue component of ear cartilage, has been observed when chondrocytes were treated
in vitro with ALA-PDT.15 Nevertheless, Park et al16 have
demonstrated that after 1 month of treatment with ALAPDT in human skin, the total collagen volume in the dermis significantly increased, with expression of type I and
III procollagen; this could explain the excellent cosmetic results in our patients.
Regarding the effect on cartilage, it has been shown
that chondrocytes are not destroyed by ALA-PDT, whereas
a decrease in the proportion of viable cells occurs in osteoblasts and synovial cells.15 In addition, PDT has been
shown to modulate in vitro cartilage metabolism, activating a chondroprotective program in photosensitized
cartilage in the context of osteoarthritis.17
In our patients with CDNH, topical application of
methyl aminolevulinate on the lesions resulted in a moderate fluorescence. This could be possible because it has
been shown that inflammatory tissues emit some fluorescence when ALA or methyl aminolevulinate is applied.18 Perhaps it is due to the protoporphyrin IX (PpIX)
accumulation into the inflammatory cells present on
CDNH. However, the reason for the minimal adverse ef-
(REPRINTED) ARCH DERMATOL/ VOL 146 (NO. 10), OCT 2010
1081
WWW.ARCHDERMATOL.COM
©2010 American Medical Association. All rights reserved.
Downloaded From: http://jamanetwork.com/ on 10/18/2016
fects reported by our patients could be that noncancerous cells metabolize less methyl aminolevulinate into the
photoactive PpIX than the cancerous ones, resulting in
less fluorescence and also in fewer adverse effects.19,20
We propose methyl aminolevulinate–PDT as a novel
method to treat patients with CDNH because it is noninvasive, free of adverse effects, can be reapplied if necessary, and has curative results comparable to those
achieved by existing methods. More patients have to be
treated in order to standardize PDT as the treatment of
choice for CDNH.
10.
11.
12.
13.
14.
Accepted for Publication: February 23, 2010.
Correspondence: Yolanda Gilaberte, MD, PhD, Service
of Dermatology, Hospital San Jorge, Av Martı́nez de
Velasco, 34, 22004 Huesca, Spain (ygilaberte@salud
.aragon.es).
Author Contributions: All authors had full access to all
of the data in the study and take responsibility for the
integrity of the data and the accuracy of the data analysis. Study concept and design: Gilaberte. Acquisition of data:
Gilaberte, Frias, and Pérez-Lorenz. Analysis and interpretation of data: Gilaberte and Pérez-Lorenz. Drafting of
the manuscript: Gilaberte. Critical revision of the manuscript for important intellectual content: Gilaberte, Frias,
and Pérez-Lorenz. Administrative, technical, and material support: Gilaberte.
Financial Disclosure: None reported.
Additional Contributions: Nick Thompson, BRTP, GDRP,
provided assistance in translating this manuscript.
15.
16.
17.
18.
19.
20.
understanding of chondrodermatitis nodularis chronica helices: the perichondrial vasculitis theory. Clin Otolaryngol. 2009;34(2):147-150.
Yoshinaga E, Enomoto U, Fujimoto N, Ohnishi Y, Tajima S, Ishibashi A. A case
of chondrodermatitis nodularis chronica helicis with an autoantibody to denatured type II collagen. Acta Derm Venereol. 2001;81(2):137-138.
Motta S, Monti M. Photodynamic therapy: a promising treatment option for autoimmune skin ulcers: a case report. Photochem Photobiol Sci. 2007;6(11):
1150-1151.
Nowis DST, Legat M, Issat T, Jakobisiak M, Golab J. The influence of photodynamic therapy on the immune response. Photodiagn Photodyn Ther. 2005;
2(4):283-298.
Karrer S, Bosserhoff AK, Weiderer P, Landthaler M, Szeimies RM. Keratinocytederived cytokines after photodynamic therapy and their paracrine induction of
matrix metalloproteinases in fibroblasts. Br J Dermatol. 2004;151(4):776-783.
Wang I, Andersson-Engels S, Nilsson GE, Wårdell K, Svanberg K. Superficial blood
flow following photodynamic therapy of malignant non-melanoma skin tumours measured by laser Doppler perfusion imaging. Br J Dermatol. 1997;
136(2):184-189.
Egli RJ, Di Criscio A, Hempfing A, et al. In vitro resistance of articular chondrocytes to 5-aminolevulinic acid based photodynamic therapy. Lasers Surg Med.
2008;40(4):282-290.
Park M, Sohn S, Lee E, Chan Kim Y. Photorejuvenation induced by 5-aminolevulinic acid photodynamic therapy in patients with actinic keratosis: a histologic
analysis. J Am Acad Dermatol. 2010;62(1):85-95.
Sullivan LG, Hasan T, Wright M, Mankin HJ, Towle CA. Photodynamic treatment
has chondroprotective effects on articular cartilage. J Orthop Res. 2002;20
(2):241-248.
Redondo P, Marquina M, Pretel M, Aguado L, Iglesias ME. Methyl-ALA-induced
fluorescence in photodynamic diagnosis of basal cell carcinoma prior to Mohs
micrographic surgery. Arch Dermatol. 2008;144(1):115-117.
Grapengiesser S, Ericson M, Gudmundsson F, Larkö O, Rosén A, Wennberg AM.
Pain caused by photodynamic therapy of skin cancer. Clin Exp Dermatol. 2002;
27(6):493-497.
Lindeburg KE, Brogaard HM, Jemec GB. Pain and photodynamic therapy.
Dermatology. 2007;215(3):206-208.
Submissions
REFERENCES
1. Moncrieff M, Sassoon EM. Effective treatment of chondrodermatitis nodularis
chronica helicis using a conservative approach. Br J Dermatol. 2004;150(5):
892-894.
2. Greenbaum SS. The treatment of chondrodermatitis nodularis chronica helicis
with injectable collagen. Int J Dermatol. 1991;30(4):291-294.
3. Taylor MB. Chondrodermatitis nodularis chronica helicis: successful treatment
with the carbon dioxide laser. J Dermatol Surg Oncol. 1991;17(11):862-864.
4. Kromann N, Høyer H, Reymann F. Chondrodermatitis nodularis chronica helicis
treated with curettage and electrocauterization: follow-up of a 15-year material.
Acta Derm Venereol. 1983;63(1):85-87.
5. Long D, Maloney ME. Surgical pearl: surgical planing in the treatment of chondrodermatitis nodularis chronica helicis of the antihelix. J Am Acad Dermatol.
1996;35(5, pt 1):761-762.
6. Rajan N, Langtry JA. The punch and graft technique: a novel method of surgical
treatment for chondrodermatitis nodularis helicis. Br J Dermatol. 2007;157
(4):744-747.
7. Lawrence CM. The treatment of chondrodermatitis nodularis with cartilage removal alone. Arch Dermatol. 1991;127(4):530-535.
8. Santa Cruz DJ. Chondrodermatitis nodularis helicis: a transepidermal perforating disorder. J Cutan Pathol. 1980;7(2):70-76.
9. Upile T, Patel NN, Jerjes W, Singh NU, Sandison A, Michaels L. Advances in the
(REPRINTED) ARCH DERMATOL/ VOL 146 (NO. 10), OCT 2010
1082
Clinicians, residents, and fellows are invited to submit
cases of challenges in management and therapeutics to
this section. Cases should follow the established pattern. Manuscripts should be prepared double-spaced with
right margins nonjustified. Pages should be numbered
consecutively with the title page separated from the text
(see Instructions for Authors [http://archderm.ama-assn
.org/misc/ifora.dtl] for information about preparation of
the title page). Clinical photographs, photomicrographs, and illustrations must be sharply focused and submitted as separate JPG files with each file numbered with
the figure number. Material must be accompanied by the
required copyright transfer statement (see authorship
form [http://archderm.ama-assn.org/misc/auinst_crit
.pdf]). Preliminary inquiries regarding submissions for
this feature may be submitted to Edward W. Cowen, MD,
MHSc ([email protected]). Manuscripts should be
submitted via our online manuscript submission and review system (http://manuscripts.archdermatol.com).
WWW.ARCHDERMATOL.COM
©2010 American Medical Association. All rights reserved.
Downloaded From: http://jamanetwork.com/ on 10/18/2016