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\begin{document}

\title{Alemtuzumab-induced petechia and epistaxis in a patient with relapsing
remitting multiple sclerosis; A case report}



\author[1]{Farhad Mahmoudi}%
\author[1]{Sayed Ali Emami}%
\author[1]{Farid Masaeli}%
\author[2]{Najmeh Rayatpisheh}%
\affil[1]{Isfahan University of Medical Sciences}%
\affil[2]{Shahrekord University of Medical Science}%


\vspace{-1em}



  
  \date{June 04, 2024}


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\textbf{Alemtuzumab-induced petechiae and epistaxis in a patient with
relapsing remitting multiple sclerosis; A case report}

Farhad Mahmoudi\textsuperscript{1*}, Sayed Ali Emami\textsuperscript{1},
Farid Masaeli\textsuperscript{1}, Najmeh Rayatpisheh\textsuperscript{2}

\textsuperscript{1} School of Medicine, Isfahan University of Medical
Sciences, Isfahan, Iran

\textsuperscript{2}School of Medicine, Shahrekord University of Medical
Sciences, Shahrekord, Iran

Corresponding author*

Farhad Mahmoudi

School of Medicine,

Isfahan University of Medical Sciences,

Isfahan, Iran

Email: farhad.mg116@gmail.com

Abstract: This case report presents a 58-year-old woman with Multiple
Sclerosis (MS) who developed petechiae and epistaxis, rare side effects
following Alemtuzumab treatment. While these reactions are infrequent,
heightened awareness among healthcare providers is essential as
Alemtuzumab gains popularity in MS treatment. Recognizing and managing
such hypersensitivity reactions promptly is crucial for improved patient
care. 1.Introduction Multiple Sclerosis (MS) is an autoimmune disease
that affects the central nervous system. The course of the disease
varies among individuals, leading to a wide range of symptoms and
patterns of presentation. Additionally, there are other conditions, such
as radiologically isolated syndrome, which can progress to MS(1). While
there is no curative therapy for this condition, certain drugs can
modify the course of the disease and improve the prognosis and quality
of life for patients.

Disease-modifying treatments (DMTs) are the preferred treatment option
for patients with MS. Alemtuzumab is an intravenously administered DMT
drug that has been available since 2014 for the treatment of patients
with multiple sclerosis who have not responded adequately to two or more
DMTs. It is a recombinant DNA-derived humanized monoclonal antibody that
selectively binds to the CD52 antigen on B and T lymphocytes, depleting
them from the bloodstream. This drug has been described as a safe and
effective treatment with minimal side effects for patients with
relapsing-remitting multiple sclerosis.(2)

While there are few studies on the cutaneous adverse effects of
Alemtuzumab, in this study, we report the first case of an MS patient
treated with Alemtuzumab who developed drug-induced petechiae and
epistaxis.

2. Case presentation

A 58-year-old Caucasian woman with relapsing-remitting multiple
sclerosis, who had no previous medical conditions, presented to the
emergency department due to muscle spasms and stiffness in her right
foot. Neurological examination revealed weakness in her right lower limb
with 3/5 muscle strength. She was diagnosed with MS at the age of 26
through an MRI and had previously been on weekly Interferon-beta (IFNb)
treatment. During acute MS attacks, she received intravenous
corticosteroids. Despite being on disease-modifying therapies (DMTs),
she experienced more relapses in the last year, and her Expanded
Disability Status Scale (EDSS) was 3. During the current
hospitalization, the patient underwent brain and cervical spinal MRI,
which revealed the appearance of new periventricular white active
plaques in addition to previous black old lesions.

Considering the progression of her disease condition, she was started on
treatment with Alemtuzumab at a dose of 12mg/day IV. There were no drug
reactions, and after completing the treatment, her muscle spasms and
stiffness resolved, and the patient was discharged from the hospital.

The day after, the patient came to the hospital to receive the second
dose of the drug. While receiving the treatment, her condition remained
stable, and she did not experience any notable symptoms. However, one
day after finishing the first dose, the patient started to experience a
gradual appearance of petechiae on her upper and lower limbs, chest,
shoulders, and back. Moreover, a few minutes later, she developed
epistaxis. Her blood pressure and heart rate were 127/73 and 87,
respectively. The patient denied any previous history of eczema, skin
issues, or respiratory allergies.

Dermatology was consulted to investigate the possible causes of
petechiae, and ENT was consulted to manage and evaluate the epistaxis.
Despite applying pressure to the nostrils and placing ice on the
forehead, the epistaxis did not cease. Consequently, the patient
underwent posterior nasal packing, which successfully halted the
bleeding.\selectlanguage{english}
\begin{figure}[H]
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\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

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\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

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\textbf{Figure 1} : Cutaneous drug reaction lesions. Petechiae in a
58-year-old Caucasian woman on left antecubital (A) and lower back (B)
one day after receiving the second dose of Alemtuzumab.

3. Discussion

Alemtuzumab is known as one of the medications used in patients with
relapsing-remitting Multiple Sclerosis who have not responded to other
drugs. This medication has some side effects, such as headache, rash,
itching, fever, fatigue, hypothyroidism, redness of the face and neck,
and more.(3)

There are many underlying causes that can lead to the development of
generalized petechiae, including prolonged straining, infectious
diseases and adverse effects of medications. Similarly, there are
several reasons for epistaxis, such as nose picking, dry air, trauma to
the nose, and medication side effects. Laboratory tests and a physical
examination of the patient ruled out all of these causes except for the
medication's adverse effect.

Adverse skin reactions to drugs typically begin within 12 to 24 hours
after exposure.(4)

Cuker et al. reported a case series of six patients with MS treated with
Alemtuzumab, resulting in the development of Immune Thrombocytopenia
(ITP). Five of these patients achieved complete remission after
treatment, while one unfortunately succumbed to the condition,
underscoring the need for serious consideration of this adverse
effect.(5)

The patient's symptoms manifested one day after receiving the second
dose of Alemtuzumab, making a drug reaction a highly plausible
explanation for these symptoms. Although rare

To the best of our knowledge, this is the first case report of
generalized petechiae and epistaxis following treatment with
Alemtuzumab, which was completely resolved after treatment. This case
report suggests that Alemtuzumab may induce changes that lead to
epistaxis, as nasal bleeding is not routinely observed in MS patients.

4. Conclusion

Generalized petechiae and epistaxis are rare side effects of Alemtuzumab
treatment in MS patients. However, as the use of Alemtuzumab in MS
treatment increases, healthcare providers should recognize and
understand this adverse reaction pattern to improve clinical management
and inform patients about potential adverse effects.

Further research endeavors are imperative to investigate potential
underlying factors within the MS patient population that might render
them more susceptible to adverse effects such as generalized petechiae
and epistaxis following Alemtuzumab treatment.

\textbf{Declarations}

\textbf{Conflict of Interest}

The authors have no conflicts of interest to declare.

\textbf{Funding}

No funding was received for this article.

\textbf{Ethics Approval}

The patient has been de-identified. Any images used do not permit the
identification of the individual. Otherwise, there are no ethical
concerns in this manuscript. There was no ethics approval required for
this manuscript.

\textbf{Consent to participate}

Written informed consent was obtained from the patient to publish this
report in accordance with the journal's patient consent policy and with
institutional guidelines.

\textbf{Written Consent for publication}

All of the authors have provided their consent to publication.

\textbf{Availability of data and material~}

All of the data and material are available

\textbf{Code availability}

Not applicable

\textbf{Authors' contributions}

\textbf{Farhad Mahmoudi} : Conceptualization; investigation;
methodology; supervision; writing -- original draft; writing -- review
and editing.\textbf{Sayed Ali Emami} : writing -- original draft;
writing -- review and editing. \textbf{Farid Masaeli} : writing --
original draft; writing -- review and editing. \textbf{Najmeh
Rayatpisheh} : writing -- original draft; writing -- review and editing.

\textbf{Reference:}

1. Fereidan-Esfahani M, Mahmudi F, Jahansouz M, Weber MS, Rodriguez M.
Biomarkers in radiologically isolated syndrome: The missing piece in the
puzzle of treatment indication? Journal of the neurological sciences.
2017;375:129.

2. Wilken J, Traboulsee A, Nelson F, Ionete C, Kolind S, Fratto T, et
al. Longitudinal assessment of neurocognitive function in people with
relapsing multiple sclerosis initiating alemtuzumab in routine clinical
practice: LEM-COG study results. Multiple Sclerosis and Related
Disorders. 2023;73:104677.

3. Guarnera C, Bramanti P, Mazzon E. Alemtuzumab: a review of efficacy
and risks in the treatment of relapsing remitting multiple sclerosis.
Ther Clin Risk Manag. 2017;13:871-9.

4. Tempark T, John S, Rerknimitr P, Satapornpong P, Sukasem C.
Drug-Induced Severe Cutaneous Adverse Reactions: Insights Into Clinical
Presentation, Immunopathogenesis, Diagnostic Methods, Treatment, and
Pharmacogenomics. Front Pharmacol. 2022;13:832048.

5. Cuker A, Coles AJ, Sullivan H, Fox E, Goldberg M, Oyuela P, et al. A
distinctive form of immune thrombocytopenia in a phase 2 study of
alemtuzumab for the treatment of relapsing-remitting multiple sclerosis.
Blood. 2011;118(24):6299-305.

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