Keywords
COVID-19 vaccines - adverse effect - lymphedema - secondary lymphedema - surgical
procedures
Introduction
After the outbreak of coronavirus disease 2019 (COVID-19), millions of doses of COVID-10
vaccine were administrated globally. Among them, more than 2,500 million doses of
the BNT162b2 (Pfizer Inc., New York, NY, United States and BioNTech, Mainz, Germany)
vaccine were administrated until 2021.[1] Lymphedema is a rare adverse effect of COVID-19 vaccination, which was reported
in several studies. Both lower extremity and upper extremity lymphedemas were reported.[2]
[3]
[4] Furthermore, outbreaks of lymphedema after COVID-19 vaccination in breast cancer
patients and frequent lower leg cellulitis after vaccination have also been reported.[5]
[6] In summary, although its incidence is relatively rare, lymphedema after COVID-19
vaccine certainly exists, and treatment option is not reported well.
Lymphedema is a condition caused by mechanical or intrinsic disruption of lymphatic
flow. Surgical treatment options for the lymphedema are divided into two categories:
ablative and physiologic surgeries. Ablative surgery can be represented by the Charles
procedure and liposuction, which remove hypertrophied fat tissue and fibrosis induced
by the chronic condition of lymphedema. Physiologic surgery includes lymphaticovenous
anastomosis (LVA), lymph node-to-vein anastomosis (LNVA), and vascularized lymph node
transfer (VLNT). Physiologic surgery nowadays plays the main role in surgical treatment
of lymphedema. However, in advanced stage of lymphedema, excess adipose tissue is
hard to be removed with physiologic surgery.[7] In those cases, liposuction is reported to be effective in reducing the volume and
improving the quality of life.[8]
In this case report, we present a case of secondary lymphedema that occurred after
the vaccination with the Pfizer (BNT162b2) vaccine including the booster dose. The
condition was successfully treated with a combination of physiologic surgery (LVA)
and ablative surgery (liposuction).
Case
Informed consent was obtained from the patient for the publication of this case report
and any accompanying images. The patient was thoroughly informed about the purpose
of the report, the nature of the information to be disclosed, and the potential implications
of its publication. The patient understood their participation was voluntary and had
the right to withdraw consent at any time without any impact on their medical care.
The patient provided written consent, agreeing to share their medical case for educational
and research purposes.
An 80-year-old female patient presented to the plastic surgery clinic with right upper
extremity edema with pitting and firm change on lateral and posterior aspects of the
upper arm and the forearm ([Fig. 1]). There was no history of trauma at the affected side of the arm and trunk nor the
operative history. The patient got vaccination for COVID-19 18 months before the visit.
It was the secondary vaccination with BNT162b2 (Pfizer-BioNTech), and edema occurred
on the same side of the arm where the vaccine was administrated. The edema started
3 days after vaccination. The patient had multiple events of cellulitis and received
intravenous antibiotics. Then the patient was referred to the rehabilitation medicine
department and received compression treatment using compression bandage, which was
prescribed from the rehabilitation medicine department for 1 year. However, response
to the treatment was refractory. Then the patient was referred to the plastic surgery
department. The patient got admission from the Ministry of the Health and Welfare
of Korea about the relationship between edema and vaccination as an adverse effect.
Fig. 1 (A, B) Preoperative findings. Ext., extremity; Inj., injection; Lt., left; Rt., right.
To exclude the possible cause of the lymphedema, chest computed tomography (CT) was
taken; however, there was no evidence of any malignancy. As a preoperative workup,
upper extremity lymphoscintigraphy and magnetic resonance lymphangiography (MRL) were
taken. In lymphoscintigraphy, increased dermal backflow at the distal forearm of the
affected side and absent uptake at the ipsilateral axillary lymph node was found,
which was correlated with signs of lymphedema ([Fig. 2]). MRL revealed multiple dilated lymphatic vessels surrounding the left wrist and
extending to the forearm along with diffuse dermal backflow at the dorsum of the hand
and mid-forearm. The circumferential size of the patient and bioelectric impedance
test are described in [Table 1].
Fig. 2 Preoperative lymphoscintigraphy.
Table 1
Circumference and bioimpedance analysis data of the patient (cm, ± cubital fossa)
|
BMI
|
BIA[a]
|
+ 15
|
+ 10
|
+ 5
|
−5
|
−10
|
−15
|
Volume (cm3)
|
|
Pre-op
|
27.0
|
|
|
Affected
|
|
5.23
|
33.5
|
34.0
|
35.0
|
32.0
|
30.3
|
28.3
|
2,285.98
|
|
Normal
|
|
1.99
|
27.0
|
23.5
|
20.0
|
20.5
|
17.5
|
15.0
|
1,082.01
|
|
Post-op 3 mo
|
25.6
|
|
|
Affected
|
|
3.09
|
28.0
|
27.0
|
26.0
|
23.5
|
22.0
|
19.0
|
1,335.19
|
|
Normal
|
|
2.16
|
26.0
|
23.0
|
21.0
|
21.0
|
17.5
|
15.5
|
1,050.36
|
|
Post-op 8 mo
|
25.6
|
|
|
Affected
|
|
2.98
|
25.5
|
24.0
|
22.5
|
22.5
|
22.0
|
20.0
|
1,242.24
|
|
Normal
|
|
1.94
|
26.0
|
23.0
|
21.0
|
21.5
|
17.5
|
15.5
|
1,050.36
|
a Bioelectric impedance analysis: extracellular water/total body water.
For the patient, as there was no operative history on the axillary area, LVA at the
wrist level and liposuction for the posterolateral aspect of the forearm and the upper
arm were planned. Before the operation, the lymphatic vessel was traced using ultrasonography
and indocyanine green (ICG) lymphangiography. Then the incision site was determined
according to the preoperative tracing. At two incisions on the wrist, two ectatic
lymphatic vessels within thin walls were found, measuring 0.4 and 0.6 mm. Successful
LVA was performed in a side-to-end manner. After the anastomosis, ICG washout to the
anastomosed vein could be seen ([Fig. 3]). Then, ultrasound-assisted liposuction was performed using the tumescent technique,
resulting in the removal of a total of 850 mL of the fibrotic tissue and fat. After
operation, immediate compression was applied with a double-layered compression bandage
(Deflate, HS Healing Solution Limited, Tsimshatsui, Hong Kong).
Fig. 3 (A, B) The picture after the lymphaticovenous anastomosis. (C, D) Indocyanine green lymphography of each anastomosis site.
The circumference of the affected arm was reduced by 8 cm at the upper arm and 8.3 cm
at the distal forearm at 8 months of follow-up. The estimated arm volume was reduced
from 2,285.98 to 1,242.24 cm3 (reduction rate 54.34%; [Fig. 4]). The bioelectric impedance analysis of extracellular fluid of the affected limb
was reduced from 5.23 to 2.98. [Fig. 5] shows the lymphoscintigraphy findings at 8 months of follow-up. The patient continued
the compression therapy using a compression bandage until the last follow-up.
Fig. 4 (A, B) Eight-month postoperative findings.
Fig. 5 Postoperative lymphoscintigraphy (8 months post-op). ANT, anterior; Ext., extremity;
Inj., injection; Lt., left; Rt., right.
Discussion
The cause-and-effect relationship of upper extremity lymphedema and COVID-19 vaccination
should be carefully judged. There are limited reports of secondary lymphedema occurring
after COVD-19 vaccination. Interestingly, there are numerous reports of lower extremity
lymphedema, but there is only one report of upper extremity lymphedema. The case report
of upper extremity lymphedema documented the development of edema following the Pfizer-BioNTech
mRNA vaccine booster, which is the same as our case.
Vaccine-induced lymphadenopathy, resulting from antigen transmission to the lymph
node, is suggested as a pathophysiology of lymphedema following vaccination.[9] According to the literature, lymphadenopathy caused by vaccination can aggravate
lymphatic drainage, especially in vulnerable patients, which can lead to the development
of lymphedema. Furthermore, some studies suggest that the COVID-19 mRNA vaccination
may be linked to an inflammatory response to hyaluronan.[10]
[11] Lymphatics are the primary pathway for hyaluronan drainage, of which dysfunction
may result in hyaluronan accumulation.[12] These may be the possible mechanism of mRNA COVID-19-vaccine-induced lymphedema.
Several studies reported lymphedema and cellulitis following COVID-19 vaccinations.[3]
[5] However, there are no reports of successful treatment of secondary lymphedema after
COVID-19 vaccination, either surgically or nonsurgically. In this case, considering
the previous failure of physical treatment including compression, surgical treatment
was attempted. With meticulous preoperative workup and planning, successful treatment
could be achieved.
In the follow-up lymphoscintigraphy, overall dermal backflow was increased compared
to the preoperative study. There are some debates about the dermal backflow pattern
in lymphoscintigraphy. Dermal backflow was deemed a sign of lymphedema; however, its
absence is considered backwardly, as a sign of most advanced stage of lymphedema.[13] Furthermore, there is report that the surgical outcome of lymphedema is better in
the cases with dermal backflow at lymphoscintigraphy compared with the cases without
dermal backflow.[14] According to a study, treatment decisions should be based on both the clinical symptom
and the severity of dermal backflow.[15] Therefore, we conclude that increased dermal backflow after surgery can be a favorable
sign of clinical improvement.
It is interesting to note that edema in the affected hand dorsum and fingers was significantly
reduced with prominent wrinkle even if the operation including liposuction was not
performed on the hand dorsum. This finding indicates that surgical management of lymphedema
can not only benefit the operated region but also improve overall lymphatic washout
throughout the whole affected limb. However, as lymphedema is a deteriorating condition,
surgical options should be provided to the patients along with decongestive treatment.
Conclusion
Lymphedema is a rare side effect of COVID-19 vaccination with limited treatment options.
With precise surgical planning, secondary lymphedema that occurred after COVID-19
vaccination could be successfully treated surgically.
