SKIN

March 2020 Volume 4 Issue 2

BRIEF ARTICLES

Successful Treatment of Pityriasis Rubra Pilaris with Brodalumab

Umair Khan1, Nahla Shihab MD2, Robert G. Phelps MD3, Mark Lebwohl MD4

1Medical Student, Eastern Virginia Medical School, Norvolk, VA
2Clinical Dermatology Fellow, Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY
3Professor and Director, Department of Dermatopathology, Icahn School of Medicine at Mount Sinai, New York, NY
4Professor and Chairman, Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY

Pityriasis Rubra Pilaris (PRP) is a rare
papulosquamous inflammatory dermatosis
of unknown etiology that may affect skin,
nails, and hair. PRP is extremely rare with
an estimated incidence of 1/5000 and often
mistaken for erythrodermic psoriasis1. The
condition mostly affects adults in their sixth
or seventh decade of life with no predilection
for genders and is subdivided into six
different subtypes based on clinical features,
age of onset and prognosis.2,3 We present
the case of a patient with type I (classic
adult onset) PRP who achieved complete
resolution after initiation with combination
therapy of brodalumab and methotrexate.

A 62-year-old gentleman with a family
history of psoriasis presents with a twenty-

year history of intermittent redness and
dryness of the hands, scalp, and groin that
receded with over the counter medications.
In the past two years, he noticed that the
patches became persistent and
progressively worse. The patient was
diagnosed with plaque psoriasis by his
previous dermatologist and failed to improve
with the use of topical steroids, a topical
calcineurin inhibitor, and topical vitamin D3
analogue. Despite a year on these topical
treatments, the rash continued to spread
predominantly to his face, trunk, and
extremities, and his dermatologist decided to
start systemic medications. The first
combination consisted of cyclosporine and
ustekinumab for three months with no visible
improvement. The biologic was then
changed to ixekizumab for another three
months displaying only minor improvement.
Finally, the dose of cyclosporine was
increased from 350mg to 400mg and the
patient started on guselkumab, which lead to
noticeable improvement. On week nine of
this regimen, cyclosporine was stopped

INTRODUCTION

CASE REPORT

Pityriasis Rubra Pilaris (PRP) is a rare inflammatory skin disease with highly variable clinical
appearance. Treatment of PRP remains a challenge and has been mostly guided by case
reports and case series. We report the first case of pityrisis rubra pilaris that is successfully
treated with combination therapy of brodalumab and methotrexate.

ABSTRACT

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March 2020 Volume 4 Issue 2

when the patient developed liver toxicity that
was attributed to the cyclosporine; within
days of cessation, the patient developed a
severe and rapid exacerbation of the skin
and new onset scalp hair loss.

The patient then presented to our clinic with
generalized erythematous-orange scaly
patches with islands of sparing (Figure 1A).
Based on his clinical presentation we
diagnosed him as classic adult onset
Pityriasis Rubra Pilaris (PRP).

A skin biopsy was obtained from his right
upper arm. The epidermis was acanthotic
with mild spongiosis. There were foci of
parakeratosis accentuated around hair
follicles. The parakeratosis showed both a
horizontal and vertical alternating pattern.
Foci of acantholysis were present. The
features were consistent with pityriasis rubra
pilaris with secondary spongiotic change
(Figure 2).

We decided to start him on brodalumab
210mg every two weeks and on week six of
treatment, we also added methotrexate
25mg every week. By week twelve of
initiating brodalumab (Figure 1B), the patient
displayed significant clinical improvement.
Long-term remission continued through six
months of combination therapy of
brodalumab and methotrexate with no
adverse events.

Figure 1A. Patient at his initial presentation to our
clinic.

Figure 1B. Patient at 12 weeks of brodalumab
treatment.

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March 2020 Volume 4 Issue 2

Figure 2. Acanthothic, mild spongiosis, with foci of
parakeratosis horizontal and vertical alternating
pattern

Pityriasis Rubra Pilaris and plaque psoriasis
are two distinct erythemato-squamous skin
diseases that are often challenging to
differentiate. Ross et al. did a multinational
study of 100 patients that showed only 26%
of patients were correctly diagnosed as
having PRP at the time of enrollment, with
the most common initial diagnoses reported
as being either psoriasis or eczema.4 On
average, this delayed the correct diagnosis
by 29 months from initial presentation4.
Clinically, patients with classic adult-onset
PRP typically present with a fine orange-red
scaling eruption that is associated with
erythroderma, palmoplantar keratoderma
and a cephalocaudal progression of

coalescing plaques with islands of sparing.
Complete remission is achieved
spontaneously within three years of onset in
80% of cases, whereas recurrence occurs in
20% of cases.2 In comparison, plaque
psoriasis presents with diffuse coarse silvery
scales attached to an erythematous base.
PRP can also present with additional
cutaneous features such as nails that are
thickened, discolored, and ridged, whereas
psoriasis patients display nail changes such
as nail pitting, the oil drop sign, and distal
onycholysis. The scalp involvement in both
psoriasis and PRP may include dandruff and
scaly scalp, as well as hair shedding; the
atypical form of PRP is more often
associated with alopecia and lesions
localized to the lower extremities.5-7 On
histopathology, type I PRP demonstrates
orthokeratosis with spotty parakeratosis,
epidermal acanthosis, intact granular layer,
and mild perivascular lymphohistiocytic
infiltrates in the dermis. In psoriasis, the
granular layer is often absent or very thin4.
Thus, the time-course, clinical presentation,
and histopathology are crucial for
distinguishing PRP from plaque psoriasis.

We present the first case of a patient with
classic adult onset PRP who failed several
biologics and immunosuppressants but was
able to achieve complete resolution with
combination therapy of brodalumab and
methotrexate. Brodalumab is a human
monoclonal antibody against the interleukin-
17 receptor A (IL-17A) approved in 2017 by
the Food and Drug Administration for the
treatment of moderate to severe plaque
psoriasis. Feldmeyer et al. reported a case
of biopsy proven PRP and found
upregulated expression of proinflammatory
cytokines including T17 helper cells (Th17)
cytokines IL-17A, IL-17F, and IL-22 and
tumor necrosis factor (TNF), IL-6, IL-12, IL-
23, IL-1β.8 Analysis of the PRP patient’s skin
sample after treatment with ustekinumab

DISCUSSION

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March 2020 Volume 4 Issue 2

showed decreased levels of TH17 cytokines
with clinical and histopathologic
improvement of the disease.8 Methotrexate
is a second line monotherapy for PRP that
disrupts folate metabolism and downstream
synthesis of thymidine. In a selection of
published cases, type I PRP patients
displayed a 50% treatment response rate to
methotrexate alone9. Although no studies
exist on the efficacy of brodalumab and
methotrexate, PRP data from select
published cases demonstrate biologics offer
a similar or higher response rate in
comparison to isotretinoin and
immunosuppressants.10-12 The excellent
response of this patient to combination of
brodalumab and methotrexate, introduces
an additional biologic in the potential
treatment options for pityriasis rubra pilaris.

Treatment options for pityriasis rubra pilaris
(PRP) are limited and often unsatisfactory.
Brodalumab in combination with
methotrexate might be a promising
therapeutic agent for patient with PRP.

Conflict of Interest Disclosures: None

Funding: None

Corresponding Author:
Nahla Shihab MD
Department of Dermatology
Icahn School of Medicine at Mount Sinai
5 E 98th Street, New York, NY 10029
Phone: 212-241-9728
Fax: 212-987-1197
Email: nahla.shihab@gmail.com

References:
1. Wang, D., Chong, V.CL., Chong, WS. et al. Am

J Clin Dermatol (2018) 19: 377.
https://doi.org/10.1007/s40257-017-0338-1

2. Roenneberg, S, Biedermann, T. Pityriasis rubra
pilaris: algorithms for diagnosis and
treatment. J Eur Acad Dermatol
Venereol 2018; 32( 6): 889– 898.

3. Griffiths, W. (1980), Pityriasis rubra pilaris*.
Clinical and Experimental Dermatology, 5: 105-
112. doi:10.1111/j.1365-2230.1980.tb01676.x

4. Ross NA, Chung H, Li Q, Andrews JK, Keller
MS, Vitto J. Epidemiologic, clinicopathologic
diagnostic and management challenges of
pityriasis rubra pilaris: a case series of 103
patients. JAMA Dermatol. 2016;152(6):670-675

5. Wain T, Choy B, Satchell AC, Woods JA, Frew
JW. Secukinumab in pityriasis rubra pilaris: A
case series demonstrating variable response
and the need for minimal clinical datasets.
JAAD Case Rep. 2018;4(5):500–505.
Published 2018 May 7.
doi:10.1016/j.jdcr.2018.02.007

6. Albert, M. R. and Mackool, B. T. (1999),
Pityriasis rubra pilaris. International Journal of
Dermatology, 38: 1-11. doi:10.1046/j.1365-
4362.1999.00513

7. Klein A, Landthaler M, Karrer S. Pityriasis
Rubra Pilaris. American Journal of Clinical
Dermatology. 2010;11(3):157–170.
doi:10.2165/11530070

8. Feldmeyer L, Mylonas A, Demaria O, et al.
Interleukin 23-helper T cell 17 axis as a
treatment target for pityriasis rubra pilaris.
JAMA Dermatol. 2017;153(4):304-308.

9. Barth, D. , Harth, W. , Treudler, R. and Simon,
J. C. (2009), Successful treatment of pityriasis
rubra pilaris (type 1) under combination of
infliximab and methotrexate. JDDG: Journal
der Deutschen Dermatologischen Gesellschaft,
7: 1071-1073. doi:10.1111/j.1610-
0387.2009.07154.x

10. Wasilewska A, Winiarska M, Olszewska M,
Rudnicka L. Interleukin-17 inhibitors. A new era
in treatment of psoriasis and other skin
diseases. Postepy Dermatol Alergol.
2016;33(4):247–252.
doi:10.5114/ada.2016.61599

11. Napolitano M, Abeni D, Didona B. Biologics for
pityriasis rubra pilaris treatment: A review of
the literature. Journal of the American
Academy of Dermatology. 2018;79(2):353-
359.e11. doi:10.1016/j.jaad.2018.03.036

12. Moretta G, De Luca EV, Di Stefani A.
Management of refractory pityriasis rubra
pilaris: challenges and solutions. Clin Cosmet
Investig Dermatol. 2017;10:451–457.
Published 2017 Nov 9.
doi:10.2147/CCID.S124351

CONCLUSION

https://doi.org/10.1007/s40257-017-0338-1