Pancytopenia as a first presentation of late-onset SLE; a case report

Abstract

Introduction
Systemic Lupus Erythematosus is a systemic immune disease that classically occurs in young to middle-aged women and may present with cutaneous, renal, hematologic, neurological, and/or other symptoms at the time of diagnosis. Late-onset Systemic Lupus Erythematosus or Systemic Lupus Erythematosus in the elderly is a subtype that differs from classic Systemic Lupus Erythematosus in terms of age group, clinical symptoms, organ involvement and severity.

Case presentation
A 63 years old female noted to have pancytopenia. The patient was diagnosed with lupus upon obtaining clinical presentations and serological marker, along with high titers of the antinuclear antibody and/or anti-double-stranded DNA antibody. The patient was managed with glucocorticoids and mycophenolate mofetil therapy, which led to a rapid response.

Discussion
Late-onset SLE accounts for 2–12% of SLE patients with a minimum age of onset of 50 years and older, leading to significant delays in diagnosis. Late-onset SLE differs from early-onset SLE in terms of gender and ethnicity prevalence, clinical symptoms and signs, development of organ damage, disease activity and severity, and prognosis .Some studies have also shown that late-stage SLE patients have higher rates of RF and anti-Ro/anti-La antibody positivity, lower complement titer, and higher incidence of elevated creatinine and decreased creatinine clearance .First-line treatment of pancytopenia is glucocorticoid. In refractory cases, rituximab and immunosuppressants can be used.

Conclusion
It is important to assess any unusual presentation of Systemic Lupus Erythematosus when clinical suspicion remains high and conducting further laboratory and imaging investigation.

Full text

Pancytopenia as a first presentation of late-onset
systemic lupus erythematosus: a case report
Ghina Haidar, MDa,*, Naram Khalayli, MDb, Tasneem Drie, MDa, Mhd Homam Safiah, MDc, Maysoun Kudsi, MD, PhDa
Introduction: Systemic lupus erythematosus (SLE) is a systemic immune disease that classically occurs in young to middle-aged
women and may present with cutaneous, renal, haematologic, neurological, and/or other symptoms at the time of diagnosis. Late-
onset SLE or SLE in the elderly is a subtype that differs from classic SLE in terms of age group, clinical symptoms, organ involvement
and severity.
Case presentation: A 63-year-old female noted to have pancytopenia. The patient was diagnosed with lupus upon obtaining
clinical presentations and serological marker, along with high titres of the antinuclear antibody and/or anti-double-stranded DNA
antibody. The patient was managed with glucocorticoids and mycophenolate mofetil therapy, which led to a rapid response.
Discussion: Late-onset SLE accounts for 2–12% of SLE patients with a minimum age of onset of 50 years and older, leading to
significant delays in diagnosis. Late-onset SLE differs from early-onset SLE in terms of sex and ethnicity prevalence, clinical
symptoms and signs, development of organ damage, disease activity and severity, and prognosis .Some studies have also shown
that late-stage SLE patients have higher rates of RF and anti-Ro/anti-La antibody positivity, lower complement titre, and higher
incidence of elevated creatinine and decreased creatinine clearance. First-line treatment of pancytopenia is glucocorticoid. In
refractory cases, rituximab and immunosuppressants can be used.
Conclusion: It is important to assess any unusual presentation of SLEs when clinical suspicion remains high and conducting further
laboratory and imaging investigation.
Keywords: elderly SLE, mycophenolate mofetil, pancytopenia, prednisone, SLE, thrombocytopenia
Introduction
Systemic lupus erythematosus (SLE) is a systemic immune disease
of unknown aetiology that classically occurs in young to middle-
aged women
[1]
. Frequent symptoms include fever, joint pain,
weight loss, and fatigue. In addition, other systemic organs
symptoms may find at the disease onset or develop as the disease
progresses
[2]
. Late-onset SLE was found to occur in patients over
50–60 years of age
[1]
. Although rare and not frequent, the term
geriatric SLE is used to distinguish it from classic SLE
[1]
. Less than
10% of patients may initially experience a single severe symptom
such as kidneys or central nervous system involvement
[3]
. The
spectrum of haematologic manifestations in SLE is very wide and
includes lymphopenia, anaemia, thrombocytopenia, or pancy-
topenia, and in some cases, lymphadenopathy and/or splenome-
galy may occur. However, many of these changes have
multifactorial causes and must be considered when determining
the appropriate treatment approach
[4]
. We report a case of an
elderly woman diagnosed with late-onset SLE with pancytopenia.
We hope that this report will be useful for future medical pro-
fessionals in diagnosing and treating this disease.
Our case is compliant with SCARE 2023 criteria
[5]
, and this
work is submitted on the research registry dashboard.
Case history/examination
A 63-year-old female with a past medical history of hypertension,
presented to the outpatient clinic in January 2023, with recurrent
oral ulcer, fever of 38.2°C*, and fatigue for the past three months.
HIGHLIGHTS
•Late-onset systemic lupus erythematosus (SLE) accounts
for 2–12% of SLE patients with a minimum age of onset of
50 years and older, leading to significant delays in
diagnosis.
•Late-onset SLE differs from early-onset SLE in terms of sex
and ethnicity prevalence, clinical symptoms and signs,
development of organ damage, disease activity and sever-
ity, and prognosis.
•It is important to assess any unusual presentation of SLE
when clinical suspicion remains high.
Departments of
a
Rheumatology,
b
Psychiatry, Faculty of Medicine, Damascus
University, Damascus and
c
Syrian Private University, Daraa, Syria
Sponsorships or competing interests that may be relevant to content are disclosed at
the end of this article.
Published online 6 March 2024
*Corresponding author. Address: Rheumatology, Faculty of Medicine, Damascus
University, University’s location: Almazzeh Street, Damascus 963 11, Syria.
Tel.: +963 991 898 337. E-mail: gtghinahaidar@gmail.com (G. Haidar).
Received 21 October 2023; Accepted 19 February 2024
Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. This is an
open access article distributed under the terms of the Creative Commons
Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is
permissible to download and share the work provided it is properly cited. The work
cannot be changed in any way or used commercially without permission from the
journal.
Annals of Medicine & Surgery (2024) 86:3025–3028
http://dx.doi.org/10.1097/MS9.0000000000001891
’
Case Report
3025

Medications before admission were amlodipine 10 mg, and
aspirin 81 mg.
The physical examination including the musculoskeletal
examination, skin examination was unremarkable except for
pallor seen on the conjunctiva, and ulcers on the lips (Fig. 1). Her
blood pressure was 135/82 mmHg with a pulse of 76 beats per
min. No enlargement in lymph nodes was observed. No hepato-
spelomegaly was found.
Laboratory examination revealed leukopenia: 2300 mm
3
(n=4000–1100), anaemia: haemoglobin 8.3 g/l (n:12–14), and
thrombocytopenia:132 000) (n=150 000–400 000),iron value
48 mcg/dl (n=60–170), total iron binding capacity 298 mcg/dl
(n=240–450), serum ferritin 87 ng/ml (n=12–150), direct
coombs was negative, reticulocyte 1% (n=0.5–2.5%),vitamin B6
4.2 ug/l (n=3.4–65.2), vitamin B12645 pg/ml (1 n=60–950),
vitamin B1 3.2 μg/dl (n=2.5–7.5), vitamin D 23 ng/ml (n=20
and 40), elevated inflammatory marker: C-reactive protein (CRP)
23.8 mg/dl (n<6), and erythrocyte sedimentation rate128 mm/h
1
)
(n=0–20).The rest of the chemical tests were normal. Protein
electrophoresis showed a polyclonal peak on gamma. Bone
marrow aspiration was compatible with pancytopenia, with no
evidence of malignancies or atypical cells, normocytic normo-
chromic red blood cells, leukopenia, and thrombocytopenia, with
normal maturation and proliferation (Fig. 2).
The patient’s chest X-ray showed no acute cardiopulmonary
abnormality. A computed tomography (CT) scan of the chest
abdomen and pelvis was also ordered, which showed no
abnormalities.
Further, the workup revealed a strongly positive antinuclear
antibody (ANA) screen (1:320 titres, homogenous pattern) with
normal anti-Sm, anti-SS-A (Ro), anti-SS-B (La), anti-Scl-70, anti-
Jo-1, anti-dsDNA, and C3 and C4 levels.
Differential diagnosis, investigation and treatment
Additionally, cryoglobulins, antineutrophil cytoplasmic anti-
bodies (ANCA), and anti-GBM antibodies. Virology including
EBV, parvovirus, herpes simplex 1/2, HIV, and hepatitis panels
was all negative. Blood and urine cultures were negative.
The patient was diagnosed to have SLE, due to the positive
ANA, in addition to fever, fatigue, recurrent oral ulcers, anaemia,
thrombocytopenia, and leukopenia , and the role out of other
causes.
In line with the recommendations, the patient has started
prednisone 60 mg once daily, and 200 mg/d hydroxychloroquine,
with improvement of fatigue, absence of fever, and increased level
of white blood cells (3600 mm
3
), haemoglobin (8.5 g/l), platelet
(152 000), in addition to decreases in ESR (98 mm/h
1
and CRP
(13.3 mg/dl) levels after 15 days.4 weeks later, the patient had no
clinical complaints, and she gained 2 kg of weight. The laboratory
tests were white blood cells (5200 mm
3
), haemoglobin (8.9 g/l),
platelet (252 000 mmm), ESR (45 mm/h1 and CRP (3.4 mg/dl)
levels. We had begun to taper the predlone dose 5 mg/wk, and
continued on 200 mg/d hydroxychloroquine, with a follow-up
duration every 3 months.
Outcome and follow-up
In August during a routine follow-up, after 6 months of disease
onset, she had no clinical complaints, and she gained 10 kg of
weight Her laboratory tests were white blood cells (9600 mm
3
),
haemoglobin (9.6 g/l), platelet (348 000), ESR (32 mm/h1 and
CRP (1.3 mg/dl) levels. She continued on 200 mg/d
hydroxychloroquine.
Discussion
SLE often affects young women
[1]
. Our patient is a 63-year-old
Syrian woman. For patients who initially present with atypical
symptoms, the American College of Rheumatology/European
League against Rheumatism (ACR)/EULAR) 2019 criteria may
be helpful in diagnosis, which requires at least six clinical
symptoms and positive serological markers with an ANA greater
than 1/80 to diagnose SLE
[4]
, as in our patient. In addition to
being ANA1/160 positive, our patient had fever, malaise, oral
ulcers, leukopenia, anaemia, and thrombocytopenia.
Late-onset SLE accounts for 2–12% of SLE patients with a
minimum age of onset of 50 years and older, leading to significant
delays in diagnosis
[3]
. The period from symptom onset to diag-
nosis has been reported to be up to 60 months for late-onset SLE,
compared to 19–24 months for adult-onset SLE
[2,3]
. Late-onset
SLE differs from early-onset SLE in terms of gender and ethnicity
prevalence, clinical symptoms and signs, development of organ
damage, disease activity and severity, and prognosis
[3]
. These
differences are due to changes in sex hormones as well as age-
related variations in environmental and/or host factors that
contribute to disease expression
[6]
. Pancytopenia is a significant
Figure 1. Ulcers on the lower lip.
Figure 2. Pancytopenia.
Haidar et al. Annals of Medicine & Surgery (2024) Annals of Medicine & Surgery
3026

risk factor for morbidity and mortality in SLE and therefore
requires aggressive treatment
[4]
.
Some studies have also shown that late-stage SLE patients have
higher rates of RF and anti-Ro/anti-La antibody positivity, lower
complement titre, and higher incidence of elevated creatinine and
decreased creatinine clearance
[7]
. All lupus patients should
receive hydroxychloroquine at dose not exceeding 5 mg/kg/d
[8]
.
During chronic maintenance therapy, glucocorticoids should be
reduced to less than 7.5 mg/d and discontinued if possible
[9]
.
Immunomodulatory drugs such as methotrexate, azathioprine,
and mycophenolate may accelerate glucocorticoid taper/dis-
continuation
[1]
. Research on belimumab, rituximab, calcineurin
inhibitors, and IFN-blocking agents has advanced in the recent
period
[10]
. Belimumab should be considered for persistently
active or recurrent disease. Rituximab or cyclophosphamide may
be considered for organ-threatening, refractory disease
[11]
.
Higher complete remission rates and a more favourable safety
profile suggest that low-dose IL-2, obinutuzumab, rituximab, and
belimumab may be superior to the current control as treatments
for lupus nephritis
[12]
. The interferon (IFN) pathway has been
extensively studied in the context of autoimmunity pathogenesis,
given that multiple genetic polymorphisms are associated with an
increased risk of developing SLE. The elevation in IFN levels
promotes the survival and differentiation of B cells by inducing
BAFF
[10]
. Calcineurin inhibitors such as voclosporin, cyclospor-
ine, and tacrolimus act directly against T lymphocytes, aiming to
decrease their activation and the release of cytokines resulting
from it. These drugs are used as a second-line treatment in
combination with mycophenolate mofetil
[13]
. First-line treatment
of pancytopenia is glucocorticoid. In refractory cases, rituximab
and immunosuppressants can be used
[11–13]
.
Induction therapy with glucocorticoids can suppress inflam-
mation, whereas maintenance therapy with immunosuppressants
can reduce immune-mediated organ damage
[14]
. However, these
patients require less frequent immunosuppression due to their
lower incidence of nephritis
[15]
. Our patient was treated with
discontinued predrone 60 mg per day and hydroxychloroquine
200 mg per day. Fortunately, the prognosis of newly diagnosed
(SLE) patients has improved significantly in recent decades
[6]
.
However, it is important to emphasize that late-onset SLE has less
systemic involvement than classic SLE. Patients with late-onset
SLE were more likely to die from treatment complications and
sepsis
[16]
. Age older than 50 years, male sex, and low C3 levels
may be associated with an increased risk of death
[17]
. According
to a study by Boddaert et al.
[6]
, there was no late-onset SLE with
haematologic manifestations. We found two cases with late-onset
SLE with nephritis in the literature
[6,18]
. A case of pancytopenia
and macrophage activation syndrome
[17]
. The key finding from
our case is to consider the diagnosis of SLE in elderly patients with
pancytopenia. Other diagnostic procedures such as serology,
imaging, and renal biopsy should be performed when possible.
Conclusion
Late-onset SLE or SLE in the elderly is a subtype that differs from
the classic SLE in age group, clinical presentation, involvement of
organs, and disease severity.
Underscores the importance of acknowledging any abnormal
presentation of SLE when clinical suspicion remains high and
conducting further investigation.
Ethical approval
This Case Series was approved by The Ethical approval was given
by the Ethical committee of the Faculty of Medicine, Damascus
University (CD: 7823,2023).
Consent
Written informed consent was obtained from patient for pub-
lication and any accompanying images. Copies of the written
consent are available for review by the Editor-in-Chief of this
journal on request.
Source of funding
None.
Author contribution
N.K. wrote the discussion, G.H. wrote the abstract and the
results, M.H.S. wrote the discussion, T.D. examined the patient,
and M.K. re-write and reviewed the study acknowledgements
given by any of the authors.
Conflicts of interest disclosure
The author declares no conflicts of interest.
Research registration unique identifying number
(UIN)
1. Name of the registry: Ghina Hiader.
2. Unique Identifying number or regiistration ID: research
registry9585.
3. Hyperlink to your specific registration (must be publicly
accessible and will be checked): https://www.researchregis
try.com/browse-theregistry#home/registrationdetails/
652154daa9e51e0028c57b44/.
Guarantor
Ghina Hiader.
Data availability
The data used to support the finding of the study are available
from the corresponding author upon request.
Provenance and peer review
Not commissioned, externally peer-reviewed.
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