Allergic Contact Dermatitis To Clostridiopeptidase A With A Nummular Eczema-Like Spread

122 FOTI ET AL.
Allergic contact dermatitis to clostridiopeptidase A

with a nummular eczema-like spread
Caterina Foti | Gianluca Calianno | Silvia Mazzotta | Fabrizio Guarneri |

Paolo Romita
1
Department of Biomedical Science and Human Oncology, Dermatological Clinic, University of Bari, Bari, Italy
2
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
Correspondence
Professor Caterina Foti, Unit of Dermatology, Department of Biomedical Science and Human Oncology, University of Bari, Policlinico, Piazza Giulio Cesare,
11 I-70124 Bari, Italy.
Email: caterina.foti@uniba.it
K E Y W O R D S : allergic contact dermatitis, case report, chloramphenicol, clostridiopeptidase A, collagenase I, leg ulcers, nummular eczema
Topical medications used for the treatment of venous leg ulcers are a
well-known cause of allergic contact dermatitis (ACD).1 Among these, topi-
cal drugs containing proteolytic enzymes (used for wound debridement)
are rarely involved.2,3 We herein report a case of severe ACD caused by
clostridiopeptidase A, also known as collagenase I.
CASE REPORT
A nonatopic 64-year-old woman presented to our attention for the onset

of a diffuse crusted eczematous dermatitis with nummular aspects
(Figure 1). The patient reported that the eruption had started to appear
about 2 weeks after the application of a topical ointment containing chlor-
amphenicol 1% and clostridiopeptidase A 60 U.I. (Iruxol, Smith & Nephew
GmbH, Hamburg, Germany) under occlusion with a zinc oxide bandage,
prescribed by her physician to treat a venous ulcer on her left leg. The skin
lesions appeared around the leg ulcer and then spread within 3 weeks to
both lower limbs, the upper limbs, and trunk, with nummular eczema-like
aspects. Her physician already prescribed oral therapy with amoxicillin–
clavulanate (875 + 125 mg twice daily) for 6 days; however, there was no
improvement of the skin lesions. Use of the topical ointment was immedi- F I G U R E 1 (A) Eczematous lesions around the leg ulcer and (B)
ately discontinued, and topical application of mometasone furoate once nummular eczema-like spreading; (C) positive patch test to Noruxol
“as is” on day 4
daily resulted in healing of the eczematous lesions in 2 weeks. Four weeks
after the resolution of the dermatitis, patch tests were performed with the paraffin, and white petrolatum; Smith & Nephew GmbH, Hamburg,
SIDAPA (Società Italiana di Dermatologia Allergologica Professionale e Germany), liquid paraffin, and white petrolatum, yielding positivity
Ambientale) baseline series (FIRMADiagent, Florence, Italy), a piece of the only to Noruxol (++; Figure 1). Based on these findings, we diag-
zinc oxide bandage, and the ointment used by the patient. Patch nosed ACD to clostridiopeptidase A. Ten healthy individuals were
tests were applied on the back and left under occlusion for 2 days patch tested with Iruxol and Noruxol with negative results.
with Haye's Test Chambers (Haye's Service B.V., Alphen aan den
Rijn, The Netherlands) on Soffix tape (Artsana, Grandate, Italy).
Readings were performed on day (D) 2 and D4 according to DI SCU SSION
guidelines,4 and showed a positive reaction to para-
phenylenediamine (++, past relevance) and Iruxol ointment (++). ACD caused by topical medications is a well-known, but probably
Subsequently, patch tests were performed with chloramphenicol underestimated and misdiagnosed complication.5 We herein reported
5% pet. and Noruxol (containing clostridiopeptidase A, liquid a case of severe ACD caused by clostridiopeptidase A, a proteolytic
FAYBUSOVICH ET AL. 123
enzyme widely used in wound and ulcer care. While chloramphenicol OR CID
is a well-known sensitizer,6 clostridiopeptidase A has rarely been Caterina Foti https://orcid.org/0000-0001-6196-9788
2,3
reported as the culprit of ACD. Nummular eczema is usually a mani- Fabrizio Guarneri https://orcid.org/0000-0003-0805-8496
festation of atopic dermatitis, but contact allergy has also been dem- Paolo Romita https://orcid.org/0000-0002-5559-9722
onstrated to be associated with nummular eczema-like aspects.7
To our knowledge, this is the first case of ACD to clostridiopeptidase RE FE RE NCE S
A with a nummular eczema-like spread. 1. Raudonis T, Vankeviciute RA, Lideikaite A, Grigaityte AG, Grigaitiene J.
We speculate that the application of the medication under occlusion Contact sensitization in patients with chronic leg ulcers: results of a 5-year
retrospective analysis. Adv Skin Wound Care. 2019;32(12):558-562.
could have favoured contact sensitization and lymphatic and/or hematoge-
2. Foti C, Conserva A, Casulli C, Scrimieri V, Pepe ML, Quaranta D. Con-
nous dissemination, which are proposed mechanisms for ACD spreading.8 tact dermatitis with clostridiopeptidase a contained in Noruxol oint-
Beyond the peculiar clinical manifestations, our case highlights that con- ment. Contact Dermatitis. 2007;56(6):361-362.
tact sensitization to topical medications containing clostridiopeptidase A, 3. Lisi P, Brunelli L. Extensive allergic contact dermatitis from a topical enzy-
matic preparation (Noruxol). Contact Dermatitis. 2001;45(3):186-187.
although rare, should be always borne in mind by physicians.
4. Stingeni L, Bianchi L, Hansel K, et al. Italian guidelines in patch testing -
adapted from the European Society of Contact Dermatitis (ESCD). G
ACKNOWLEDGEMEN TS Ital Dermatol Venereol. 2019;154(3):227-253.
Open Access Funding provided by Universita degli Studi di Bari Aldo Moro 5. Garval E, Plee J, Lesage C, Grange-Prunier A, Bernard P, Perceau G.
Frequency of contact sensitization to modern dressings used to treat
within the CRUI-CARE Agreement. [Correction added on 25 May 2022,
chronic leg ulcer. Ann Dermatol Venereol. 2018;145(5):339-346.
after first online publication: CRUI funding statement has been added.]
6. Romita P, Stingeni L, Hansel K, et al. Allergic contact dermatitis caused
by chloramphenicol with prurigo nodularis-like spreading. Contact Der-
CONF LICT S OF INTE R ES T matitis. 2019;80(4):251-252.
All the authors have no conflict of interest to declare. 7. Bonamonte D, Foti C, Vestita M, Ranieri LD, Angelini G. Nummular eczema
and contact allergy: a retrospective study. Dermatitis. 2012;23(4):153-157.
8. Lachapelle JM. Allergic contact dermatitis: clinical aspects. Rev Environ
AUTHOR CONTRIBUTIONS Health. 2014;29(3):185-194.
Caterina Foti: Conceptualization (equal); data curation (equal); supervi-
sion (equal); writing – review and editing (equal). Gianluca Calianno: Con-
How to cite this article: Foti C, Calianno G, Mazzotta S,
ceptualization (equal); data curation (equal). Silvia Mazzotta: Data
Guarneri F, Romita P. Allergic contact dermatitis to
curation (equal); formal analysis (equal). Fabrizio Guarneri: Data curation
clostridiopeptidase A with a nummular eczema-like spread.
(equal); formal analysis (equal); supervision (equal). Paolo Romita: Con-
Contact Dermatitis. 2022;86(2):122-123. doi:
ceptualization (equal); data curation (equal); formal analysis (equal); super-
10.1111/cod.13982
vision (equal); validation (equal); writing – review and editing (equal).
Mepolizumab for treating systemic allergic dermatitis with

hypereosinophilia likely secondary to a nickel/
cobalt-containing coronary artery stent
Paul Faybusovich1 | Jordan Lim2 | Michael D. Ioffreda2 | Taha Al-Shaikhly1

1
Section of Allergy, Asthma & Immunology, Department of Medicine, Penn State College of Medicine, Hershey, Pennsylvania, USA
2
Department of Dermatology, Penn State College of Medicine, Hershey, Pennsylvania, USA
Correspondence
Dr Paul Faybusovich, Penn State College of Medicine, 500 University Drive, PO Box 850, Hershey, PA 17033, USA.
Email: pfaybuso@nyit.edu
K E Y W O R D S : case report, cobalt, drug-eluting stent, hypereosinophilia, interleukin 5 (IL-5), medical device, mepolizumab, nickel, systemic
allergic dermatitis
Systemic allergic dermatitis (SAD) from endovascular devices is not secondary to an unretrievable nickel/cobalt-containing drug-eluting coro-
uncommon.1 We present a patient with SAD and hypereosinophilia likely nary artery stent, who responded to anti-interleukin (IL)-5 therapy.

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122 FOTI ET AL.

Allergic contact dermatitis to clostridiopeptidase A

Caterina Foti | Gianluca Calianno | Silvia Mazzotta | Fabrizio Guarneri |

A nonatopic 64-year-old woman presented to our attention for the onset

Mepolizumab for treating systemic allergic dermatitis with

Paul Faybusovich1 | Jordan Lim2 | Michael D. Ioffreda2 | Taha Al-Shaikhly1

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