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\begin{document}

\title{Severe mononeuritis multiplex in eosinophilic granulomatous
polyangiitis: Case Report}



\author[1]{Reem Al Saadi}%
\author[1]{Sarah AlQassimi}%
\author[1]{Mohamed Abuzakouk}%
\author[1]{Ahmad Alduaij}%
\affil[1]{Cleveland Clinic Abu Dhabi}%


\vspace{-1em}



  
  \date{May 24, 2024}


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\begin{abstract}
\emph{Background}: This report describes a 48-year-old man who presented
with a month history of weakness and paraesthesia associated with severe
pain of all four limbs. Initially diagnosed and treated as GBS due to
the severity of his extremity weakness, later discovered to be EPGA
\emph{Objective:} Mononeuritis multiplex should not be underestimated or
overlooked in the setting of diagnosing EGPA and requires prompt
treatment with biologics to limit the permanent consequences on
patient's quality of life in regards to developing limb weakness and
pain. \emph{Conclusion}: Although peripheral neuropathy and namely
mononeuritis multiplex is not the most common feature of EGPA, it is
important to consider it in order not to delay treatment with biologic
agents that as seen in our patient can both halt the progress of the
disease as well as give the patient a better quality of life.%
\end{abstract}%



\sloppy


\emph{Severe mononeuritis multiplex in eosinophilic granulomatous
polyangiitis: Case Report}

Reem Al Saadi MD.\textsuperscript{1}, Sarah AlQassimi
MD.\textsuperscript{1}, Mohamed Abuzakouk MD.\textsuperscript{1}, Ahmad
Alduaij MD.\textsuperscript{2}

\textsuperscript{1}Cleveland Clinic Abu Dhabi, Department of Allergy and
Immunology.

\textsuperscript{2}Cleveland Clinic Abu Dhabi, Department of Pathology.

AlsaadR2@ClevelandClinicAbuDhabi.ae (Reem Al Saadi)

AlQasiS@ClevelandClinicAbuDhabi.ae (Sarah AlQassimi)

AbuzakM@ClevelandClinicAbuDhabi.ae (Mohamed Abuzakouk)

AlduaiA@ClevelandClinicAbuDhabi.ae (Ahmad Alduaij)

\emph{Corresponding author:} Reem Al Saadi\textsuperscript{1}

Keywords: eosinophilic granulomatous polyangiitis, mononeuritis
multiplex, mepolizumab, Nucala, monoclonal antibody, vasculitis,
neuropathy

Abbreviations: None

Funding source: None

Trial registration: Not applicable

Conflicts of interest: None

Word count: 1139

Figures: 2

Tables: None

Abstract

\emph{Background} :

This report describes a 48-year-old man who presented with a month
history of weakness and paraesthesia associated with severe pain of all
four limbs. Initially diagnosed and treated as GBS due to the severity
of his extremity weakness, later discovered to be EPGA

\emph{Objective:}

Mononeuritis multiplex should not be underestimated or overlooked in the
setting of diagnosing EGPA and requires prompt treatment with biologics
to limit the permanent consequences on patient's quality of life in
regards to developing limb weakness and pain.

\emph{Conclusion} :

Although peripheral neuropathy and namely mononeuritis multiplex is not
the most common feature of EGPA, it is important to consider it in order
not to delay treatment with biologic agents that as seen in our patient
can both halt the progress of the disease as well as give the patient a
better quality of life.

\emph{Introduction:}

EGPA, a rare yet potentially life-threatening systemic necrotizing
vasculitis affecting the small vessels systematically. This disease is
known to develop over three phases: the prodromal/allergic phase
(hallmarked by hard to treat asthma, sinusitis and allergic rhinitis)
then followed by the second eosinophilic stage with peripheral or organ
infiltrating eosinophilia and last stage being the vasculitic stage. Not
all patients develop the three however our patient did demonstrate all
three phases with the last one being the most severe manifestation
targeting the peripheral nerves.

\emph{\textbf{Clinical Course}:}

48-year-old gentleman known case of moderate-severe chronic
rhinosinusitis and mild asthma who initially presented to an outside
hospital with a progressive 4-week history of paresthesia and weakness
of all four extremities, more prominently on the right compared to the
left. He reports testing positive for COVID-19 infection one month
prior, for which he was treated with a 5-day course of favipiravir. He
noted after taking the first dose of medication, he started to develop
paresthesia involving right hand that spread to his forearm then soon
developed weakness and pain as well. The paresthesia and weakness
progressed to involve the right leg, left arm and left leg after a few
days.

During his stay at the outside hospital, he was diagnosed with
Guillain-Barre syndrome based on nerve conduction study that showed
demyelinating motor neuropathy and conduction block of the right median,
right ulnar, right tibial and left peroneal nerves. Additionally, he
underwent an electromyogram that confirmed absence of motor nerve
activity in a similar distribution. He was treated with IVIG and pulse
steroid therapy for 5 days with mild improvement and was discharged
afterwards. Unfortunately, his symptoms continued to worsen to the point
he developed right wrist and bilateral foot drop, prompting his return
back to the hospital for further management.

He underwent further testing including laboratory work up that revealed
leukocytosis of 19.7 x 10\textsuperscript{9}/L with neutrophilia of 8.9
x 10\textsuperscript{9}/L and eosinophilia of 7.23 x
10\textsuperscript{9}/L, elevated C3 C4 levels, negative ANA, positive
pANCA, positive cryoglobulin IgG, IgE of 1625 IU/mL, CRP of 135 mg/L,
creatinine of 69 micromol/L, microscopic hematuria and underwent a
lumbar puncture that yielded WBC of 2, high IgG, normal protein and
normal glucose levels. Imaging including MRI spine that revealed a mild
disc bulge at C3-C4 and C4-C5, MRI brachial plexus that revealed no
brachiopathy. He started on prednisolone 60 mg daily and transferred
from the outside hospital for evaluation of presumed eosinophilic
granulomatosis with polyangiitis.

On admission to our facility, physical examination revealed 0/5 power of
the distal right upper extremity (right wrist drop), 5/5 of the proximal
right upper extremity, 4/5 power of the distal left upper extremity, 5/5
power of the proximal left upper extremity, 0/5 power of the distal left
lower extremity (left foot drop), 4/5 power of the right lower extremity
and marked loss of sensation in the lower extremities bilaterally up to
the mid-shins in a stocking distribution.

He underwent nerve biopsy of the left sural nerve that later revealed
focal angiocentric acute and chronic inflammation (figure.2). He was
promptly started on mepolizumab in addition to prednisolone 60 mg in the
interim. His stay was complicated by worsening severe neuropathic pain
that required consultation of our pain management team. He was started
on a strong pain regimen. Further progression of his neurological
deficits was evidenced by a new onset right foot drop. In view of his
worsening symptoms, he was started on rituximab but unfortunately there
continued to be an increase of inflammatory markers despite this. It was
felt that he was not responding to the treatment thus far and the
decision to start on a course of IVIG with an increase of his
prednisolone from 60 mg to 90 mg was made.

After these changes, he showed both biochemical and clinical improvement
and was discharged with close follow up with Allergy and Immunology as
an outpatient (figure.1).

He was continued on mepolizumab for 2 months and tapering dose of
prednisolone but due to financial constraints, he was unable to continue
on mepolizumab. In view of his clinical improvement, he was started on
azathioprine to maintain remission of the disease and his disease has
been stable.

\emph{Discussion:}

EGPA which is also called as Churg-Strauss syndrome, an ANCA related
small vessel vasculitis presenting with a three-phase progressive course
of the following, a prodromal allergic phase of asthma and
rhinosinusitis, then eosinophilic inflammatory infiltrates develop in
the tissues and lastly a vasculitic phase such as purpura and
mononeuritis multiplex. Pathophysiology of the latter is caused by
axonal degeneration of the nerves due to ischemia caused by the
vasculitis itself.

Mononeuritis multiplex as well as peripheral neuropathy are a common
presentation in patient diagnosed with EGPA, in a large published series
about 50-60\% suffered from peripheral neuropathy and mononeuritis
multiplex was slightly more common than peripheral neuropathy, with
lower limbs being the most affected \textsuperscript{2,3} with the
peroneal, tibial, ulnar, and median nerves; being the most common nerves
to be attacked, furthermore complicated by asymmetric foot or wrist
drop, also can potentially evolve into symmetric or asymmetric
polyneuropathy; sensory deficits and neuropathic
pain\textsuperscript{4,5} as was seen in our patient.

Although this neuropathic involvement is less likely to be detrimental
compared to lung and renal involvement, it does markedly affect the
patient's quality of life. Our patient presented with paraesthesia which
then progressed to weakness of all four limbs and right wrist drop and
bilateral foot drop in a non-characteristic manner of GBS associated
with severe neuropathic pain, with notable eosinophilia and a history of
asthma, with no other organ involvement.

EGPA should always be in the differentials when thinking of treating or
diagnosing a patient with GBS as the treatment differ and may cause life
threatening complications. Accurately diagnosing EGPA is imperative due
to the known treatment delay related progression into irreversible organ
dysfunction.

Management of EGPA initially requires the use of high dose systemic
steroids with the aim to achieve and maintain clinical remission
swiftly. Second line, in cases that do not respond to steroids, other
immunosuppressants like cyclophosphamide are needed. Other promising
treatment options are biologic agents like anti-interleukin-5
mepolizumab, which was used in our patient. Prognosis of untreated EGPA
is very poor. Reported as a 5-year survival of 25\%. Whereas when
diagnosed quickly and treated appropriately, prognosis is much improved,
with study findings of 78-month survival rate at about
70-90\%\textsuperscript{6}.

Conclusion:

In conclusion, severe peripheral neuropathy is an important
manifestation of EGPA and must not be overlooked. Although peripheral
neuropathy is difficult to connect to the diagnosis of EPGA, it must be
considered as a highly possible diagnosis. Samson et al. reported that
mononeuritis multiplex as a presentation of EGPA could foretell the need
for aggressive treatment with biologic agents \textsuperscript{1},
making peripheral neuropathy an important symptom to investigate and
associate with EPGA to ensure prompt administration of treatment.

\textbf{References}

1.M. Samson, X. Pu\selectlanguage{ngerman}échal, H. Devilliers C. Ribi, P. Cohen, B. Bienvenu et
al., ``Mononeuritis multiplex predicts the need for immunosuppressive or
immunomodulatory drugs for EGPA, PAN and MPA patients without
poor-prognosis factors,'' Autoimmunity Reviews, vol. 13, no. 9, pp.
945--953, 2014.

2.C. Comarmond, C. Pagnoux, M. Khellaf, J. Cordier, M.Hamidou, J.
Viallard et al., ``Eosinophilic granulomatosis with polyangiitis
(Churg-Strauss): clinical characteristics and long-term followup of the
383 patients enrolled in the French Vasculitis Study Group cohort,''
Arthritis \& Rheumatism, vol. 65, no. 1, pp. 270--281, 2013.

3.J. Wolf, V. Schmitt, F. Palm, A. J. Grau, and R. Bergner, ``Peripheral
neuropathy as initial manifestation of primary systemic vasculitides,''
Journal of Neurology, vol. 260, no. 4, pp. 1061--1070, 2013.

4. Cattaneo L, Chierici E, Pavone L, Grasselli C, Manganelli P, Buzio C,
et al. Peripheral neuropathy in Wegener's granulomatosis, Churg-Strauss
syndrome and microscopic polyangiitis. J Neurol Neurosurg Psychiatry.
2007;78:1119--23.

5. Hattori N, Ichimura M, Nagamatsu M, Li M, Yamamoto K, Kumazawa K, et
al. Clinicopathological features of Churg-Strauss syndrome-associated
neuropathy. Brain. 1999;122(Pt 3):427--39.

6. Samson M, Puéchal X, Devilliers H, Ribi~C, Cohen P,~Stern M~et al.
Long-term outcomes of 118 patients with eosinophilic granulomatosis with
polyangiitis (Churg-Strauss syndrome) enrolled in two prospective
trials. J 2013;43(6):60--69.\selectlanguage{english}
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