4 Ohno Y, Kamiyama N, Nakamichi S, Kihara A. PNPLA1 is a transacylase
essential for the generation of the skin barrier lipid x-O-acylceramide.
Nat Commun 2017; 8: 14610.
5 Pichery M, Huchenq A, Sandhoff R et al. PNPLA1 defects in patients
with autosomal recessive congenital ichthyosis and KO mice sustain
PNPLA1 irreplaceable function in epidermal omega-O-acylceramide
synthesis and skin permeability barrier. Hum Mol Genet 2017; 26:
6 Lee E, Rahman OU, Khan MT et al. Whole exome analysis reveals a novel
missense PNPLA1 variant that causes autosomal recessive congenital
ichthyosis in a Pakistani family. J Dermatol Sci 2016; 82:46–48.
7 Ahmad F, Ansar M, Mehmood S et al. A novel missense variant in the
PNPLA1 gene underlies congenital ichthyosis in three consanguineous
families. J Eur Acad Dermatol Venereol 2016; 30: e210–e213.
8 Vahidnezhad H, Yousseﬁan L, Saeidian AH et al. Gene-targeted next gen-
eration sequencing identiﬁes PNPLA1 mutations in patients with a phe-
notypic spectrum of autosomal recessive congenital ichthyosis: The
impact of consanguinity. J Invest Dermatol 2017; 137: 678–685.
9 Zimmer AD, Kim GJ, Hotz A et al. Sixteen novel mutations in PNPLA1
in patients with autosomal recessive congenital ichthyosis reveal the
importance of an extended patatin domain in PNPLA1 that is essential
for proper human skin barrier function. Br J Dermatol 2017;177:445–455.
10 Boyden LM, Craiglow BG, Hu RH et al. Phenotypic spectrum of autoso-
mal recessive congenital ichthyosis due to PNPLA1 mutation. Br J Derma-
tol 2017;177:319–322. https://doi.org/10.1111/bjd.15570.
11 Diociaiuti A, El Hachem M, Pisaneschi E et al. Role of molecular testing
in the multidisciplinary diagnostic approach of ichthyosis. Orphanet J
Rare Dis 2016; 11:4.
Beneﬁt from reslizumab
treatment in a patient with
chronic spontaneous urticaria
and cold urticaria
Chronic urticaria (CU) is a group of common and debilitating
conditions containing both chronic spontaneous urticaria
(CSU) and chronic inducible urticarias (CIndU) including cold
While antihistamines and omalizumab are
effective treatments for both CSU and ColdU,
show insufﬁcient response to either or both of these treatments,
and additional and better therapies are needed.
Reslizumab is a humanized monoclonal anti-interleukin 5
(IL-5) antibody licensed for the treatment of severe eosinophilic
asthma. IL-5 is the major cytokine responsible for the recruit-
ment, activation and survival of eosinophils, which play a crucial
role in causing tissue and subsequent airway hyperresponsive-
ness in asthma.
Previously, we demonstrated that eosinophil
numbers are increased in the skin of CSU patients.
reported that treatment with mepolizumab, another monoclonal
antibody against IL-5, can result in the rapid remission of CSU.
Here, we report the case of a 43-year-old woman with severe
non-allergic refractory eosinophilic asthma (non-smoker, IgE
136 kU/L, skin prick test negative to pollen, mites and other
common aeroallergens, eosinophils 540/lL, FEV
predicted, asthma control test (ACT) 15 points, four asthma
exacerbations in the last year, therapy including prednisolone
50–25 mg/day, LAMA and LABA) who was successfully treated
for her asthma with reslizumab. Our patient experienced a rapid
improvement of her asthma following the ﬁrst infusion of
reslizumab (300 mg). The FEV
increased to 91%, ACT to 20
points, prednisolone was reduced to 15 mg 7 days later, cough
and night symptoms diminished in the ﬁrst 10 days.
In addition to her asthma, our patient had ColdU and CSU
with recurrent angio-oedema but without weals for 23 years.
She ﬁrst became aware of her ColdU because of a severe systemic
reaction and widespread wealing after swimming in a cold Swed-
ish lake. Subsequent provocation testing conﬁrmed ColdU.
Despite her attempts to avoid cold exposure, she experienced
cold-induced symptoms approximately weekly each winter.
Together with her ColdU, our patient also started to
experience episodes of recurrent angio-oedema without
weals, the least common of the three phenotypes of CSU.
Her swellings affected her lips, eyes, cheeks, hands and feet
and lasted for up to one day. They were accompanied by a
burning painful sensation. The frequency of these swelling
episodes over the years varied from once to twice per
month with a gradual increase over the last years. Retro-
spective assessment of her CU, both ColdU and CSU, before
reslizumab treatment by the urticaria control test (UCT)
showed uncontrolled disease with a UCT score of 6. In this
four-item validated instrument with a 0 to 16 scoring range,
a score of <12 indicates uncontrolled and ≥12 indicates
Immediately following reslizumab injection, our patient expe-
rienced substantial sustained improvement of her urticaria
symptoms, both CSU and ColdU. Four weeks after the ﬁrst
injection, her UCT score was 16, indicating complete disease
control. This score has been maintained over the last four
months of treatment with reslizumab 300 mg/month.
To our knowledge, this is the ﬁrst case of reslizumab treat-
ment of a CU patient. Before reslizumab treatment, the patient’s
poorly controlled urticaria symptoms and her need to avoid cold
exposure impacted greatly on her quality of life.
In conclusion, our observation that the anti-IL-5 antibody,
reslizumab, effectively reduces the symptoms of CSU and ColdU
suggests an axial role of eosinophils in these conditions. While a
mechanism cannot be concluded, we speculate that eosinophils
contribute to the development of weals and angio-oedema or
induce tissue hyperresponsiveness thereby reducing the thresh-
old for symptom development.
This study was supported by intramural funding.
© 2017 European Academy of Dermatology and Venereology
2018, 32, e86–e121
Letters to the Editor