Oral Vitamin A as an Adjuvant Treatment for Refractory Pityriasis
Rubra Pilaris (PRP)
Hanif Sri Utami
1*
, Benny Nelson
1
, Eyleny Meisyah Fitri
1
, Windy Keumala Budianti
1
, Endi Novianto
1
1
Department of Dermatology and Venereology Faculty of Medicine Universitas Indonesia/
Dr. CiptoMangunkusumoNational CentralGeneral Hospital, Indonesia
Keywords: Pityriasis Rubra Pilaris, Retinol, Therapy, Vitamin A
Abstract: Pityriasis rubra pilaris (PRP) is a rare and chronic papulosquamous disorder of unknown etiology that often
progresses to erythroderma and causes a disabling palmoplantar keratoderma. Genetic factors with an
autosomal dominant pattern of inheritance have been supposed to play a critical role for the induction of PRP.
Vitamin A deficiency was also believed to be related to the disorder. Treatment of PRP is mainly anecdotal,
based on case reports and case series, a feature shared by many disorders in dermatology due to their rarity.
Currently, oral retinoids and methotrexate are the first line of therapy in patients with PRP. Response to
therapy varies in each patient. We report a 46-year-old male patient with erythroderma and hyperkeratotic
palms and soles since two years ago. Histopathological findings were consistent with PRP. The patients had
been treated with several systemic therapies, yet showed poor clinical response. Clinical improvement was
seen after 16 weeks addition of oral vitamin A at a dosage of 200.000 IU daily in concurrent with 10 mg
weekly methotrexate. Evaluation of potential adverse effects was closely monitored.Oral vitamin A, an old
regimen, seems to be a favorable adjuvant treatment for refractory PRP.
1 INTRODUCTION
Pityriasisrubrapilaris (PRP) is a rare and chronic skin
disorder that often progresses to erythroderma and
causes a disabling keratoderma of the palms and
soles. The exact cause of this skin disorder remains
elusive. The impact of this skin disorder is often
devastating on patients’ quality of life. There are six
different types of PRP based on clinical presentation,
age of onset, and prognosis. The most common
clinical features are follicular hyperkeratosis,
progressing to salmon-colored erythroderma with
islands of normal skin (nappesclaires). Palms and
soles are frequently involved as waxy and thick
hyperkeratotic plaque. These typical features occur in
more than 50% of the patients of PRP and the disease
resolution usually occurs after an average period of 3
years.(Moretta G et al, 2017;Sehgal VN et al., 2008).
The management of PRP has always been
challenging. The management is predominantly
based on case reports with limited number of patients.
To date, no randomized controlled trial had been
conducted due to the scarcity of the disease. The
classical therapies include systemic therapies such as
retinoids, methotrexate, cyclosporine, and fumaric
acid. Psoralen plus ultraviolet A (PUVA)
photochemotherapy is also in use. However, response
to therapy varies from person to person, and it is not
uncommon that patients show poor response to
multiple therapies (Ross NA et al., 2016).
Oral vitamin A (retinol) at a dosage of 150,000 to
300,000 IU per day was reported beneficial in some
patients. Retinoids, its synthetic derivatives, are
considered to be the first line therapy. Isotretinoin,
acitretine, and etrenitate have been reported helpful in
some patients of PRP. They help regulate the
proliferation and differentiation of the epithelial cells.
Compared to retinol, the administration of these
synthetic agents requires lower dose.
4
However, the
prescription of these synthetic agents remains
restricted in Indonesia, so that we try oral vitamin A
as an adjunctive treatment while monitoring the side
effects.
2 CASE
A 46-year-old male patient visited the
Dermatovenerology clinic, Cipto Mangunkusumo
National Central General Hospital with erythroderma
Utami, H., Nelson, B., Fitri, E., Budianti, W. and Novianto, E.
Oral Vitamin A as an Adjuvant Treatment for Refractory Pityriasis Rubra Pilaris (PRP).
DOI: 10.5220/0009987102950298
In Proceedings of the 2nd International Conference on Tropical Medicine and Infectious Disease (ICTROMI 2019), pages 295-298
ISBN: 978-989-758-469-5
Copyright
c
2020 by SCITEPRESS Science and Technology Publications, Lda. All rights reserved
295
since two years ago. The skin eruption appeared first
on the neck, and then spread in cephalocaudal
direction to the whole body within one month. He has
sought treatment to several physicians. However,
there was no improvement on his skin lesion.
Physical examination showed generalized
salmon-colored patches with islands of normal skin.
The scaling was fine and powdery. The palms and
soles showed hyperkeratotic plaque with flexion
contracture of some fingers. Yellow discoloration of
the nails was also present. There was also ectropion
of his bilateral lower eyelids.
From histopathological findings, the epidermis
showed alternating orthokeratosis and parakeratosis,
regular acanthosis, and prominent granular layer. The
dermis showed dilated vasculatures. The patient was
diagnosed with PRP based on clinical manifestation
and histopathology examination.
The hemoglobin level was 14 g/dL, leukocytes
8,520 /L, thrombocytes 404,000 /L, SGOT (AST)
33 U/L, SGPT (ALT) 27 U/L, ureum 12 mg/dL and
creatinine 0.8 mg/dL. He received methotrexate with
weekly dosage up to 17.5 mg. Because there was no
significant improvement after five months, the
treatment was switched to another therapeutic agent.
He was given cyclosporine 4 mg/kg/day. However,
after four months the treatment was discontinued
because of no improvement.
We decided to give methotrexate with additional
oral vitamin A (retinol) to the patient. Oral
methotrexate was maintained at weekly dosage of 10
mg with 200,000 IU oral vitamin A per day. After 16
weeks, there was marked improvement clinically.
The erythematous patches became fainter and the
scaling seemed finer. The hyperkeratotic lesion on his
palms and soles also improved.
Duringmethotrexate and retinol therapy, the
evaluation of adverse effects was routinely
performed. Liver function testwas carried out
monthly. The patient was also referred to
theophthalmologist to investigate any ocular adverse
effect and to treat his ectropion.
Figure 1.Before retinol administration.Confluence of PRP
lesions leads to erythroderma with a reddish orange colors
and extensive scales (A-C). Keratoderma in PRP, palmar
(D) and plantar (E).
Figure 2.Evaluation after 16 weeks of retinol administration
revealed significant improvement. Erythroderma(A-C) and
palmo-plantar keratoderma (D-E) partially subsided.
3 DISCUSSION
Successful treatment for patients with PRP have
always been a great challenge for dermatologists.
Oral vitamin A, usually at a daily dosage of 150,000
to 300,000 IU was reported helpful. The
administration of vitamin A is able to accelerate the
shedding of keratoderma, and was reported to
B
C
A
A B C
D
E
D E
CBA
E
ICTROMI 2019 - The 2nd International Conference on Tropical Medicine and Infectious Disease
296
reducethe duration of disease. However response to
therapy varied. Clinical improvement was
experienced in one of three patients.
4
The
administration of oral vitamin A was initially based
on the hypothesis that PRP occurred as a result of
vitamin A deficiency. However, it was revealed later
that patients oftenhad normal level of vitamin A.
Other investigator proposed another hypothesis that
the lack of clinical response to vitamin A was resulted
from lack of retinol-binding protein, a specific
transport protein of vitamin A. In spite of the unclear
linkage between PRP and vitamin A metabolism, it is
well-noted that vitamin A plays a significant role in
the treatment of PRP. Clinical response to vitamin
Aseemed to be related to the pharmacological
action.(Cohen et al., 1989)
.
The first line treatment of
PRP is the oral retinoids.(Klein A et al., 2010)
Isotretinoin was reported effective both in adult and
juvenile type PRP.The clinical improvement was
experienced by 60% to 95% after 16 to 24 weeks of
isotretinoin therapy. The daily dosage varied, ranging
from 0.5 to 3.19 mg/kg. Another study reported the
lower daily dosage of 1 to 1.5 mg/kg was
adequate.Etretinate, an aromatic retinoid, was
reported helpful at a daily dosage of 1 mg/kg. Clinical
improvement was seen after 20 weeks of etretinate
therapy. Compared to isotretinoin, etretinate has
longer half-life.(Dicken CH et al., 1987)
Alitretinoin at a dosage of 30 mg per day was
reported helpful as an alternative treatment. The
therapeutic effect of alitretinoin was considered
through itsanti-inflammatory mechanism. In vitro,
alitretinoin inhibited of proinflammatory cytokines
such as TNF and IL-12/IL-23.(Amann PM et al.,
2015)
.
Vitamin A and retinoids has the same potential
adverse effectsof hypervitaminosis A such as
teratogenicity, abdominal pain, visual disturbances,
dryness, dizziness, and hypertriglyceridimia.
8
Routine laboratory tests should be performed to
monitor any adverse effects.Hypervitaminosis
vitamin A was reported in patients obtaining systemic
vitamin A more than 50,000 IU daily. However,
retinoids do not seem to disturb liver function as it is
not stored in the liver like vitamin A.
5
Administration
of oral vitamin A for treatment of PRP has been
described in previous literature and textbooks, but the
effective amount and period of vitamin A has not
been specifically described. The administration of
vitamin A is suggested only for adults. Children are
considered to be more susceptible to its toxicity.
Pregnant and childbearing-age women are also
restricted due to its teratogenic effect.(Randle HW et
al., 1980).
Antimetabolites like methotrexate is often used in
patients of PRP. Clinical improvement usually
appears after 6 weeks therapy, and complete response
is often achieved by week 12 to 16. However, patients
refractory to convential therapy often require
combination therapy with retinoids and methotrexate.
In a study, 22 patients were treated with etretinate 25-
75 mg/day or isotretinoin 40 mg twice daily. Half of
the patients also received methotrexate at a weekly
dosage of 5-30 mg. After 16 weeks, 8 of 11 patients
in combination therapy showed clinical improvement
of 50-95%.
4
However, due to teratogenicity, oral
retinoids including isotretinoin, etretinate and
alitretinoin are not available in Indonesia.
In our patient, clinical improvement did not occur
after 20 weeks of methotrexate administration as
monotherapy, yet marked improvement did appear
after 16 weeks of oral vitamin A administration in
concurrent with methotrexate at a weekly dosage of
10 mg. Liver function tests were routinely performed
as the concurrent use of methotrexate and vitamin A
increased the risk of hepatotoxicity.In this patient, we
routinely monitored the potential side effects by
clinical symptoms and laboratory markers. There was
no elevation of liver enzymes. However, there are few
similar case reports to date. Hereafter, as more cases
become accumulated, we would expect to clarify the
effective minimum dosage and optimal dosing period
of vitamin A therapy for PRP patients.
4 CONCLUSION
PRP is a rare and chronic skin disorder that often
progresses to erythroderma and causes a disabling
skin disorder. Finding a suitable management has
always been difficult. Although the linkage between
PRP and vitamin A metabolism remains intriguing
and individual clinical response to therapy exists, it is
worth to offer vitamin A therapy for patients with
refractory PRP as a favorable alternative. Careful
monitoring should be routinely performed to avoid its
potential adverse effects. Due to restricted
prescription of retinoids in some countries, oral
vitamin A is a favorable alternative for patients
without any contradictions.
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