Oral Vitamin A as an Adjuvant Treatment for Refractory Pityriasis

Rubra Pilaris (PRP)

Hanif Sri Utami

, Benny Nelson

, Eyleny Meisyah Fitri

, Windy Keumala Budianti

, Endi Novianto

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.

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

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 B C

D E

CBA

E

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reducethe duration of disease. However response to

therapy varied. Clinical improvement was

experienced in one of three patients.

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.

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.

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%.

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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