e8 Letters to the Editor

Table 2 Efficacy and safety outcomes following 12 weeks of ixek- 5 (50.0%) also experienced an AE to ixekizumab. Conversely, of
izumab treatment in patients with prior exposure to secukinumab the 21 patients who did not experience an AE to secukinumab,
Variable Value 6 (19.4) went on to experience an AE to ixekizumab. This sug-
N = 31 gests that not all patients who have an unfavourable response to
Efficacy – no. (%) secukinumab will also experience an AE with ixekizumab.
≥PASI 75 or PGA 0/1 22 (71.0) Overall, our clinical experience suggests that (i) a proportion-
Duration of secukinumab exposure: ally high number of patients with prior exposure to secuk-
4–26 weeks 4/8 (50.0) inumab will achieve efficacious outcomes following 12 weeks of
27–52 weeks 11/16 (68.8) ixekizumab treatment, (ii) safety outcomes with secukinumab
53+ weeks 7/7 (100)
do not correlate with ixekizumab safety outcomes and (iii)
Reason for stopping secukinumab:
patients with prior extended exposure to secukinumab may be
Primary non-responder 5/7 (71.4)
favourable candidates for ixekizumab therapy.
Secondary non-responder 14/18 (77.8)
This article has no funding source.
Intolerance 0/3 (0)
Non-drug related reasons 3/3 (100)
J.R. Georgakopoulos,1 M. Phung,2 A. Ighani,3 K. Lam,3
Scheduled knee surgery
J. Yeung3,4,5,6,*
Head trauma 1
Schulich School of Medicine and Dentistry, Western University, London,
Diabetic ketoacidosis
ON, Canada, 2Department of Pharmacology and Toxicology, University of
PASI values – mean  SD Toronto, Toronto, ON, Canada, 3Faculty of Medicine, University of
Secukinumab baseline 14.8  8.7 Toronto, Toronto, ON, Canada, 4Sunnybrook Health Sciences Centre,
Switching to ixekizumab 10.2  3.4 Toronto, ON, Canada, 5Women’s College Hospital, Toronto, ON, Canada,
Ixekizumab week 12 3.8  6.8 6
Probity Medical Research Inc., Waterloo, ON, Canada
Safety – no. (%) *Correspondence: J. Yeung. E-mail: jensen.yeung@utoronto.ca
Experienced one or more AE 11 (35.5) IRB statement: Ethical approval was granted by the Research Ethics
Discontinued treated due to an AE 2 (6.4) Board at Sunnybrook Health Sciences Centre (287-2010) and Women’s
Reported adverse events – no. (%) College Hospital (2010-0041-E).
Injection site reaction/erythema/pain 4 (12.9)
Postinjection systemic reaction 2 (6.4) References
Dermatitic rash (peri-orbital) 1 (3.2) 1 Hu Y, Chen Z, Gong Y, Shi Y. A review of switching biologic agents in the
Elevated liver enzymes 1 (3.2) treatment of moderate-to-severe plaque psoriasis. Clin Drug Investig 2018;
38: 191–199.
Infected epidermoid cyst 1 (3.2)
2 Georgakopoulos JR, Phung M, Ighani A, Yeung J. Efficacy and safety of
Prolonged drug eruption secondary to secukinumab 1 (3.2) switching to ixekizumab in secukinumab nonresponders with plaque pso-
Mastoid bone infection 1 (3.2) riasis: a multicenter retrospective study of interleukin 17A antagonist ther-
apies. J Am Acad Dermatol 2018. https://doi.org/10.1016/j.jaad.2018.01.
PASI, Psoriasis Area and Severity Index; PGA, physical global assessment;
003.
AE, adverse event. Primary non-responder, did not achieve PASI 75 at any
3 Griffiths CEM, Reich K, Lebwohl M, et al. Comparison of ixekizumab with
point throughout the secukinumab treatment period; Secondary non-respon-
etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and
der, achieved PASI 75 following 12 weeks of treatment, however, experi-
UNCOVER-3): results from two phase 3 randomised trials. Lancet (Lon-
enced loss of efficacy after initial response.
don, England) 2015; 386: 541–551.
4 Gordon KB, Blauvelt A, Papp KA, et al. Phase 3 trials of ixekizumab in
well to ixekizumab, the duration of exposure is likely not the moderate-to-severe plaque psoriasis. N Engl J Med 2016; 375: 345–356.
causative factor. Rather, individuals who show favourable effi-
cacy outcomes to one IL-17A antagonist and thus received treat- DOI: 10.1111/jdv.15100

ment for a longer duration may be predisposed to respond

optimally to a second IL-17A antagonist. PASI 75 or PGA of 0/1
was achieved by 71.4% (n = 5/7) of primary non-responders to
secukinumab, 77.8% (n = 14/18) of secondary non-responders,
0% (n = 0/3) who stopped due to intolerance and 100% (n = 3/3)
Cowpox virus infection in two
who stopped due to non-drug related reasons. brothers with possible
Reported AEs in our patient population were uncommon
with 35.5% (n = 11) of patients experiencing one or more AEs
human-to-human transmission
compared to 58.4% reported in RCTs.4 Similar to RCTs, injec- Editor
tion site reaction/erythema/pain was the most commonly Two 12 and 16-year-old peasant brothers were admitted to our
reported AE (present work: 12.9% (n = 4), RCTs: 16.9%). Of centre with a history of necrotic ulcers. Both of them were trea-
the 10 patients who experienced an AE to secukinumab, ted with oral and intravenous antibiotics ineffectively. The 12-

JEADV 2019, 33, e1–e48 © 2018 European Academy of Dermatology and Venereology
Letters to the Editor
year-old boy had lesions on his head since 4 weeks, which started
1 week after he played with rats and neighbour’s domestic
calves, sheep and goats. Before the eruption occurred, the patient
had subfebrile temperature and flu-like symptoms. His 16-year-
old brother had necrotic ulcers on the face. He had febrile tem-
perature 1 week after his brother developed the eruption. The
patient had close contact with his brother and a 3-year-old sister
but denied any contact with domestic or wild animals. Less
severe eruption and symptoms were reported by their mother
and sister.
On younger brother’s physical examination, ulcerated necrotic
plaque and papules, accompanied by marked, painless, erythema-
tous infiltration of surrounding tissue, were noted at the scalp and
left nostril. On the right postauricular area, few ulcerated lesions
were detected (Fig. 1). The older brother had firm, necrotic ulcers
with surrounding painless, erythematous oedema on his chin and
above the right eyebrow (Fig. 2). In both brothers head lice and
regional lymphadenopathy were observed.
Tularaemia, tuberculosis, anthrax and syphilis were excluded.
Younger patient’s complete blood count showed leucocytosis
(10.98 9 109/L), lymphocytosis (48.4%; 5.31 9 109/L), mono-
cytosis (9.3%; 1.02 9 109/L), eosinophilia (6.9%; 0.76 9 109/L)
and reactive thrombocytosis (338 9 109/L). Culture from ulcer
was positive for Pseudomonas aeruginosa. Histopathology
revealed necrotic ulcer tissue. Older patient’s complete blood
count, CRP and ESR were normal, and cultures from ulcers were
negative. The histopathological investigation showed epidermal
ulceration and dermal fibrosis with mixed infiltration of
Figure 1 Younger brother’s clinical findings and their changes
during the treatment/(a–b) clinical findings before treatment: (a) –
an ulcerated necrotic plaque and papules with surrounding pain-
less, erythematous infiltration, (b) – few ulcers on the right postau-
ricular area (c) and (d) – completely healed lesions 3 months after
discharge from our centre.
JEADV 2019, 33, e1–e48
e9
plasmocytes, neutrophils, lymphocytes and discrete eosinophils.
CPXV was confirmed by polymerase chain reaction (PCR) assay
(Robert Koch microbiology laboratory, Berlin).
Patients were treated with antiseptic wound dressings and ulcer
debridement. The younger brother received antibiotic therapy
with ciprofloxacin 250 mg b.i.d., and the older brother – with
amoxicillin 500 mg thrice daily. For the head lice, benzyl ben-
zoate 20% solution was applied for both patients up to five appli-
cations. The regional lymphadenopathy disappeared, and ulcers
healed completely with severe scarring only after 3 months.
Human CPXV infection is a sporadic disease that was reported
nearly 150 times.1,2 The natural reservoirs of CPXV are probably
rodents, which transmit the virus to cats, cows and zoo animals.
CPXV incubation period is approximately 5–14 days. The infec-
tion is transferred to humans with a direct contact with an
affected lesion in animal skin.3,4 Symptoms usually appear on
exposed skin, e.g. face, hands, arms and neck. Clinical signs are
cutaneous papules that develop into vesicles, pustules and
crusts.5–7 Cutaneous symptoms are considered capable of pro-
ducing infectious material that is contagious until the crust falls.8
CPXV infection is currently epidemiologically relevant and
will probably be more important in the future due to its increas-
ing frequency in humans. More cases of CPXV infections in ani-
mals and humans were published through Europe in recent
years.5–7,9,10 The first case in the United States with a research
laboratory-acquired human CPXV infection in a laboratory
employee who had a contact with contaminated reagents or
contaminated surfaces was reported in 2012.8
Figure 2 Older brother’s clinical findings and their changes during
the treatment/(a–b) – firm, necrotic ulcers with surrounding pain-
less, erythematous oedema above the right eyebrow and on the
chin ((b) a zoomed view of (a)), (c) – ulcers on the chin during the
treatment in our centre and (d) – completely healed lesions
3 months after discharge.
© 2018 European Academy of Dermatology and Venereology
e10 Letters to the Editor

To reduce CPXV infection frequency, prevention measure- involvement of periorbital skin.1 The well-known conditions
ments are mandatory. It is recommended to vaccinate house- manifesting with RES include neuroblastoma, systemic amyloi-
hold, domestic and zoo animals in risk areas. People of risk dosis, skull base fracture and neonatal lupus erythematosus.1–4
groups (e.g. veterinarians, animal handlers, zoo workers and To our knowledge, the occurrence of RES in Sweet syndrome
farmers) should be vaccinated either. Avoidance of contact with (SS) has not been reported to date. Two patients presenting with
infected animals or people and good hand hygiene should be RES in addition to characteristic clinical and histopathological
generally considered. Additionally, suspicious pets or domestic features of SS are presented here.
animals must be checked for any skin lesion or disease A 27-year-old man presented with a 5-day history of multiple,
symptoms and treated by veterinarians. painful, cutaneous nodules and oral ulcers. He was otherwise
healthy, and his family history was also insignificant. Ten days
G. Tamulyte,1,2,* J. Lauraitis,1 R. Ganceviciene,2 before the development of the skin lesions, he had an upper res-
J. Grigaitiene,1,2 C.C. Zouboulis3,* piratory tract infection (URTI) accompanied by a fever and was
1
Centre of Dermatovenereology, Vilnius University Hospital Santaros
given a 7-day-course of amoxicillin–clavulanate 1000 mg BID.
Klinikos, Vilnius, Lithuania, 2Clinic of Infectious Diseases and
Dermatological examination showed multiple, tender, erythe-
Dermatovenereology, Faculty of Medicine, Vilnius University, Vilnius,
matous, nodules and plaques on the extremities and trunk. In
Lithuania, 3Departments of Dermatology, Venereology, Allergology and
Immunology, Dessau Medical Center, Brandenburg Medical School
addition to the cutaneous lesions, multiple aphthous ulcers on
Theodore Fontane, Dessau, Germany the tongue and soft palate and conjunctival injection were also
*Correspondence: G. Tamulyte and C.C. Zouboulis. E-mails: noticed. Moreover, erythematous, oedematous plaques exclu-
giedrutetamulyte@gmail.com (GT) and christos.zouboulis@ sively involving the periorbital region and giving an appearance
klinikum-dessau.de (CCZ) of raccoon eyes were also remarkable (Fig. 1a–c). Laboratory
tests disclosed no abnormalities except for a mild leukocytosis
References with peripheral neutrophilia. Serologic tests for acute viral infec-
1 Amer M, El-Gharib I, Rashed A, Farag F, Emara M. Human cowpox tions including HIV, hepatitis B and C and syphilis were nega-
infection in Sharkia Governorate, Egypt. Int J Dermatol 2001; 40: 14–17.
tive, and the other possible underlying causes such as
2 Baxby D, Bennett M, Getty B. Human cowpox 1969-93: a review based
on 54 cases. Br J Dermatol 1994; 131: 598–607.
3 Haller SL, Peng C, McFadden G, Rothenburg S. Poxviruses and the evo-
lution of host range and virulence. Infect Genet Evol 2014; 21: 15–40.
4 Shchelkunov S, Marennikova S, Moyer R. Orthopoxviruses pathogenic
for humans|Springer [Internet]. Springer US, 2005: 425. URL http://
www.springer.com/gp/book/9780387253008 (last accessed: 2017 Mar 7).
5 Campe H, Zimmermann P, Glos K et al. Cowpox virus transmission
from pet rats to humans, Germany. Emerg Infect Dis 2009; 15: 777–780.
6 Ninove L, Domart Y, Vervel C et al. Cowpox virus transmission from pet
rats to humans, France. Emerg Infect Dis 2009; 15: 781–784.
7 Vogel S, Sardy M, Glos K, Korting HC, Ruzicka T, Wollenberg A. The
Munich outbreak of cutaneous cowpox infection: transmission by
infected pet rats. Acta Derm Venereol 2012; 92: 126–131.
8 McCollum AM, Austin C, Nawrocki J et al. Investigation of the first
laboratory-acquired human cowpox virus infection in the United States.
J Infect Dis 2012; 206: 63–68.
9 Cardeti G, Brozzi A, Eleni C et al. Cowpox virus in llama, Italy. Emerg
Infect Dis 2011; 17: 1513–1515.
10 Favier A-L, Flusin O, Lepreux S et al. Necrotic ulcerated lesion in a young
boy caused by cowpox virus infection. Case Rep Dermatol 2011; 3: 186–194.

DOI: 10.1111/jdv.15103

Expanding the differential

diagnosis of raccoon eyes:
Figure 1 Bilateral raccoon eyes appearance (a) in addition to aph-
sweet syndrome thous ulcerations on the oral mucosa (b) and classical nodular
Editor lesions of the Sweet syndrome on the legs (c). Histopathological
examination showed nodular neutrophilic inflammation (indicated
Among the various animal eponyms in dermatology, raccoon by an asterisk, ‘*’) in the mid- and deep dermis (H&E, 920).
eyes sign (RES) is used the characterize the prominent

JEADV 2019, 33, e1–e48 © 2018 European Academy of Dermatology and Venereology