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\begin{document}

\title{Rituximab-induced psoriasis in a patient with pemphigus vulgaris: A case
report and literature review}



\author[1]{Leila Ghadirzade}%
\author[2]{Shima Moslemi Haghighi}%
\author[3]{Soheila Nasiri}%
\author[2]{sahar dadkhahfar}%
\affil[1]{Shaheed Beheshti University of Medical Sciences}%
\affil[2]{Shahid Beheshti University of Medical Sciences}%
\affil[3]{Skin Research Center Shahid Beheshti University of Medical Sciences}%


\vspace{-1em}



  
  \date{May 21, 2024}


\begingroup
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\sloppy


\textbf{Introduction}

Psoriasis and pemphigus are two chronic inflammatory immune mediated
cutaneous disorders. Rituximab (MabThera, Rituxan) is a chimeric
murine/human anti-CD20 monoclonal antibody known as a potential drug for
treatment of pemphigus vulgaris. It is administrated via intravenous
infusion (1). Here we present a case of a 48-years-old patient affected
with pemphigus vulgaris and developed psoriatic plaques on her scalp,
trunk and arms four months after the second course of rituximab.

\textbf{Case presentation}

A 48-year-old female known and previously treated case of pemphigus
vulgaris, presented with a two month history with a pruritic scaly
plaques scattered on scalp, trunk and extremities.

She was complaining from mucocutaneous pemphigus vulgaris from 16 years
before the current presentation. She had received multiple courses of
corticosteroid pulse therapy followed by maintenance treatment with oral
prednisolone. In august 2021, the patient was admitted due to pemphigus
recurrence and treated with a course of Rituximab (two infusions of 1 gr
2 weeks apart) in addition to 30 mg of oral prednisolone. One month
later, she had complete resolution for her skin lesions. Later
prednisolone was tapered gradually.

Her physical examination showed a sharply demarcated, scaly and
erythematous plaques distributed over the scalp, retro auricular skin,
abdomen, presacral area and extensor surface of the upper and lower
extremities. Examination of nails, mucosa, and joints were normal. Skin
biopsy revealed psoriasiform acanthosis, munds of parakeratosis and
suprapapillary plate thinning. Papillary dermis showed vascular
tortuosity and perivascular lymphocytic infiltration compatible with the
diagnosis of psoriasis. Laboratory lab test including complete blood
count, lipid profile, liver function tests, urea, creatinine, ESR and
CRP were normal. Treatment for psoriasis included methotrexate 7.5
mg/week and topical clobetasol. Oral prednisolone was tapered over six
months to 2.5 mg/day. During six months' of follow up, the psoriatic
plaques had partially improved (PASI score =3.2), erythema and
induration had significantly decreased, and no other sites were
involved. Currently, she is still on methotrexate (10 mg /week) and
low-dose systemic corticosteroid therapy (prednisolone 2.5 mg daily).

\textbf{Discussion}

The exact underlying mechanism for the association of psoriasis and
pemphigus vulgaris is still unclear, but there are various hypotheses
which could clarify the relationship to some extent. For example,
Rituximab which is widely used for treatment of pemphigus vulgaris can
be a potential contributing factor for development of psoriatic plaques
in some patients.

In addition to rituximab-induced psoriasis in pemphigus vulgaris,
several psoriasis cases has been also reported in patients with
rheumatoid arthritis, non-Hodgkin's lymphoma, systemic lupus
erythematosus, granulomatosis with polyangiitis, idiopathic membranous
glomerulopathy and chronic idiopathic demyelinating polyneuropathy
disorder after receiving rituximab for controlling the underlying
disorder.

Rituximab may induce psoriasis via a variety of mechanisms. First,
rituximab leads to B-cell depletion resulting in elimination of B-cells
regulation on T-cells and therefore T-cells activation (2, 3). Rituximab
also has been shown to impair the response to infection leading to the
psoriasis development (2). Since psoriasis has been regarded as a
T-cell-driven disease, the T cell dysregulation after rituximab therapy
might be responsible for development of psoriasis (3).

According to the literature, in patients with rituximab-induced
psoriasis, nail changes, pustular and plantar psoriasis, and psoriatic
arthritis, as well as all the plaque type psoriasis were detected in
patients. Psoriasis onset varied between 10 days to 2 years after the
first dose. In our case, psoriatic lesions developed 4 months after the
second course of rituximab.

Several studies have shown a link between bullous disease and psoriasis.
Bullous pemphigoid is known as the most common auto-immune bullous
disease associated with

psoriasis (2), followed by pemphigus vulgaris, pemphigus foliaceous
(2-6), and

herpetiform pemphigus (7). On the other hand, less commonly, there are
some reports of development psoriasis in pemphigus vulgaris patients
similar to our case (8, 9).

In a recent study recorded by Balighi et al, three patients with
pemphigus vulgaris developed psoriasis, two of them did not receive
rituximab. This may also highlight another contributing factor other
than rituximab. For instant, the role of spreading epitope may be a
suggested etiology for this coincidence. According to this model many
proteins, which were not recognizable by immune system cells, become
identifiable after activation of chronic autoimmune response that leads
to a new autoimmune reaction (epitope phenomenon 1998)

In 1987 yokoo et al reported a case for pemphigus foliaceous coexistence
with psoriasis in one patient, focusing on the fact that the activation
of plasminogen is involved in acantholysis in pemphigus. Also, increased
concentrations of plasminogen activator have been detected in psoriasis
lesions.

Based on genome-wide association studies, psoriasis and pemphigus are
both related to HLA DRB1 alleles. As a result, genetic factors may also
play a remarkable role in association of these two auto-inflammatory
skin diseases.

\textbf{Table 1:} Review of literature for rituximab-induced psoriasis
for a variety of underlying disorders\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
\begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
author\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
Underlying disease\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
age\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
sex\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
Type of lesions\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
Time onset\strut
\end{minipage} & \begin{minipage}[b]{0.12\columnwidth}\raggedright\strut
treatment\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Dae-Woo Kim(4)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
non-Hodgkin lymphoma\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
6\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
male\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Psoriatic plaques on shoulder, chest, abdomen, back and scalp\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
3 month after starting rtx\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
topical corticosteroid\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
F Mielke(5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
non-Hodgkin lymphoma\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
66\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
female\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
psoriatic arthritis onycholysis tenosynovitis of the Achilles
tendon\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
6-8 weeks\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
methotrexate 15 mg/week including initial prednisolone 20 mg/d\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Z C Venables\textsuperscript{~}(6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
non-Hodgkin lymphoma\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
53\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
female\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Palmoplantar pustulosis psoriasis\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
About 2--3 weeks after each cycle\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Self-limited topical corticosteroid\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Shouvik Dass\textsuperscript{~} (7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
rheumatoid arthritis\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
17\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
female\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
scalp psoriasis onycholysis, pan-uveitis, and ruptures of the Achilles
tendon\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
6 months\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Not reported\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Markatseli TE(8)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
rheumatoid arthritis\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
55\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
female\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Plaques on arms and thighs\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
6 month after first course and 10 days after second\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Not reported\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Shouvik Dass\textsuperscript{~} (7)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
rheumatoid arthritis\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
52\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
female\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Psoriatic plaques over both knees and on the extensor surfaces of
thighs.\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
12 month\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
topical corticosteroid\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Alexandra Maria Giovanna Brunasso,(9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
rheumatoid arthritis\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
45\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
female\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Plantar pustlosis\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
3 month\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Topical clobetasol Intramuscular methotrexate at 15mg/wk\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
G M Guidelli(10)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
rheumatoid arthritis\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
69\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
female\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
~Psoriatic papuloplaques on her trunk and arms\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
three months(14 weeks after first infusion) after the second course of
rituximab\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Topical fluticasone\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Gulsen Ozen(11)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
rheumatoid arthritis\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
50\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
female\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
psoriatic patch-plaque on extremities\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Five months after 3rd cycle, 25 months after 1st infusion\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Not reported\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Sarah A Hardcastle(12)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
rheumatoid arthritis\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
49\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
female\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Plantar pustular psoriasis nail changes. Two months later itchy, scaly
patches around the ankles and heels were seen, including some
well-defined plaques\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
4 weeks\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
topical corticosteroid, topical salicylic acid, and coal\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
P Jayasekera(13)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
rheumatoid arthritis\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
80\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
female\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
plantar pustular psoriasis\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
2 years\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
tocilizumab\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Loretta Fiorillo\textsuperscript{~}(14)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
ITP\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
16-month-old\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
male\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Psoriatic plaques on the legs , arms, back, and over the scalp
over\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
7 weeks\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
course of 6 weeks Methotrexate\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Shouvik Dass\textsuperscript{~} (7)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Systemic lupus erythematosus\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
26\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
female\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Psoriatic plaques on elbows and the extensor surfaces of arms and
thighs, trunk, onycholysis\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
4 month\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
topical corticosteroid\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Maggie Ming Yee Mok\textsuperscript{~}(15)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
IDIOPATHIC MEMBRANOUS NEPHROPATHY\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
51\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
male\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Psoriatic papulopustules over trunk and limbs,\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
4 month\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
topical corticosteroid\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Hana S. Alahmar(16)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Granulomatosis with Polyangitis\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
38\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
female\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
plaques over the abdomen ,and extensor surface of the upper and lower
extremities bilaterally\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Three months after the third course of RTX (18 months from the first
course)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
subcutaneous adalimumab 40 mg every two weeks along with a topical
corticosteroid\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Filomena Russo\textsuperscript{~}(17)\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
Chronic idiopathic demyelinating polyneuropathy disorder\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textbf{Key Clinical Message:}

Acquainting medical doctors about rituximab-related cutaneous
complications like psoriasis will help them in detection and management.

\textbf{Competing interests~} The authors have no conflicts of interest
to declare.

\textbf{Funding}

This research did not receive any specific grant from funding agencies
in the public, commercial, or not-for-profit sectors

\textbf{Patient consent for publication} \textbf{~} Written informed
consent was obtained from the patient's family for publication of this
case report and any accompanying images

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Induction of psoriatic skin lesions in a patient with rheumatoid
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3. Alahmari HS, Alhowaish NY, Omair MA. Rituximab-Induced Psoriasis in a
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5. Mielke F, Schneider-Obermeyer J, D\selectlanguage{ngerman}örner T. Onset of psoriasis with
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10.1136/ard.2007.080929.

6. Venables ZC, Swart SS, Soon CS. Palmoplantar pustulosis secondary to
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7. Dass S, Vital EM, Emery P. Development of psoriasis after B cell
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Induction of psoriatic skin lesions in a patient with rheumatoid
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\textbf{Figure legend:}

\textbf{Figure 1:}

Multiple scaly erythematous plaques on abdomen\selectlanguage{english}
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