Group (N)
|
Age (M± SD)
|
Sex %
|
1
|
AL-Ansari, R. Y. (15)
|
Case report
|
2021
Saudi Arabia
|
1
|
39
|
Female
|
Allergic to a strawberry and kiwi, otherwise medically free.
|
Pfizer-BioNTech
(mRNA vaccine) first dose
|
Palms of the hands and soles of the feet itchiness that is associated with occasional redness
|
Onset: 10 days
Duration: 5 days
|
NA
|
Full blood count and biochemical: unremarkable.
IGE level: was not available
|
Treated conservatively by anti-histamine
|
The symptoms gradually resolved within five days. No hospital admission was required during her course of illness.
|
Isolated itching to palms and soles could be one of the side effects of COVID-19 vaccination (Pfizer-BioNTech)
|
2
|
Arora, P. (16)
|
Case report
|
2021
New Delhi, India
|
1
|
60
|
Male
|
Type II diabetes
mellitus and hypertension
|
COVAXIN
(inactivated)
|
Multiple grouped vesicles on an erythematous base, present
over the knee, and anterior aspect of right thigh
|
Onset: 4 days
Duration: 2 weeks
|
The combination of age and vaccination
could be the plausible explanation for reactivation of VZV in
patient
|
Tzanck smear from an intact vesicle: acantholytic cells. No
multinucleated giant cells could be seen. Skin biopsy from the vesicle: intraepidermal spongiotic vesicle containing acantholytic
cells with large vesicular nuclei neutrophils and dyskeratotic
cells.
Herpes zoster involved L2 and L3 dermatome.
|
Oral valacyclovir 1g 3 times
a day for 7 days along with topical fusidic acid for local application
twice daily
|
The lesions subsided in 2 weeks without any sequelae
or neuralgia. The patient received second dose of the same vaccine
after 4W without any adverse effects
|
-
|
3
|
Cebeci, F. (17)
|
Case report
|
2021
Istanbul, Turkey
|
1
|
82
|
female
|
hydroxychloroquine 400 mg regularly for
the last 3 years for seronegative RA,
hypertension
|
CoronaVac (Inactive virus)
|
A diffuse petechial rash was observed on both lower extremities during dermatological
examination. There were no symptoms
other than weakness and burning
in the legs
|
Onset: 1 day
Duration: 7 days
|
Hypersensitivity may result either from
the active vaccine component or one of
the other components
|
A complete blood test,
biochemical parameters, CRP, D-dimer, platelet, coagulation parameters: normal.
Urinalysis showed no signs of proteinuria
or haematuria.
hepatitis and HIV: negative.
Antinuclear antibodies, antineutrophil
cytoplasmic antibodies and cardiolipin
antibodies: normal.
Complement levels and serum proteinograms: normal. PCR and rapid IgM,
IgG antibodies for SARS-COV-
2: negative
|
Prednisolone
5 mg, which she had been using for
6 months for seronegative arthritis, was
discontinued 3 weeks before the vaccine
in order not to prevent the effect of the
vaccine.
|
The lesions regressed almost completely
after 2 days and completely disappeared
after 1 week
Therefore, we
decided to administer the second dose to
our patient 28 days after the first dose and no skin reaction was observed after
the second dose.
|
Vaccine-associated
hypersensitivity
reactions are not infrequent; however,
IgE or complement-mediated
anaphylactic
or serious delayed-onset
T cell-mediated
systemic reactions are extremely rare.
The most frequent signs of delayed-type reactions are cutaneous eruptions such as maculopapular petechial
rash.
|
4
|
Farinazzo, E. (18)
|
Case series
|
2021
North east Italy
|
46
|
Mean:44.39
SD: 12.36
(18-31]:6
(31-44]:16
(44-57]:17
(57-70):7
|
Female:41 (89%)
Male: 5 (11%)
|
-
|
BioNTech/ Pfizer vaccine
(mRNA based)
|
Male: itchiness 40% Diffuse urticarial 20% Pityriasis rosea-like rash on the neck, upper limbs, and trunk20%
Erythema at the inoculation site 20%
Female:
Itchiness 29%
Urticarial rush 19% Erythema 31% Swelling 14% Morbilliform eruption 2% fixed drug eruption 2%
Chilblain-like rash 2% Pityriasis rosea-like rash 2%
Malar rash 2%
painful wheals 9%
Herpes Zoster 5%
chest urticarial rash with chilblain-like manifestations on the first and third finger of one foot 2%. malar erythema, an erythematous macular rash of the hands, a fixed drug eruption 10% resembling pityriasis rosea4%
|
60 h-10 days after injection
|
Regarding the urticarial manifestations, Polyethylene glycol-
2000 (PEG-2000), an excipient of the vaccine, may play a role
|
-
-
|
For 3
subjects: not applying the second dose
|
Course was mostly mild and self-limiting. Only one patient
with urticaria (nr. 45) required intravenous steroid treatment.
|
Cutaneous adverse reactions triggered by
Comirnaty_-BioNTech/Pfizer are seldom but appear similar to
those reported during SARS-CoV-2 infections.
|
5
|
Hoff, N. P. (19)
|
Case series
|
2021
Germany
|
11
|
50.09±13.18
|
Male:
2 (18%),
female:
9 (82%)
|
Patient no. 7 (female 44) had obesity as a comorbidity factor
|
Moderna (mRNA-1273) vaccine
|
(Painful) edema: 72%; Erythema: 63%; Induration: 27%; Soreness 18%; Mild pruritus 18%; Lymphadenopathy 18%; Urticarial plaque and cutaneous tenderness, painful burning and cutaneous tenderness: 9%
All the
reported lesions were near the injection site.
|
Onset: 3-12 days after vaccination
Duration: 1-4 days
|
“COVID-arm”
|
Histology:
superficial and deep perivascular dermatitis,
with scattered eosinophils and intraluminal neutrophil
accumulation
|
Oral antihistamines (2 patient)
Topical glucocorticoids
+ oral antihistamines (2 patients)
No treatment (7 patients)
|
All the cutaneous manifestations resolved
within 14 days. None of the skin reactions after the first dose of the vaccine prevented the administration of the second
dose. There were no long-term cutaneous sequelae in any of the affected individuals.
|
Further investigations on the precise molecular and cellular mechanisms underlying
this cutaneous pathology is needed to understand
why and when rare adverse events may occur after RNA
vaccines.
|
6
|
Hussain, K. (20)
|
Case report
|
2021
London, UK
|
1
|
62
|
Female
|
Metastatic melanoma and
related CPI therapy
(Nivolumab and ipilimumab) myocarditis. new onset of
symptoms consistent with Raynaud disease (RD)
|
Pfizer (BioNTech- COVID-19 RNA vaccine)
|
Mucosal membrane involvement; rash
grade 4; erythrodermic with superficial
blistering noted on the patient’s thigh and chest
|
2 days (grade 3 eruption)
3-7 days (grade 4
eruption)
|
Initial
drug rash that resolved on cessation of the co-trimoxazole, then developed a more severe form of the rash
reaction to the co-trimoxazole, during
which drug-specific memory T cells were formed;
COVID-19 vaccination caused a surge in
the T-cell-driven response from skin-homing CD4+ T cells
generated by the original delayed hypersensitivity reaction.
(Recent CPI therapy,
which in itself reduces the self-tolerance response of
T cells and boosts effector T-cell responses)
|
Skin
biopsy: drug-induced lichenoid dermatitis
with scattered apoptotic bodies and lymphocytic infiltrate; Direct immunofluorescence: negative;
An infective/ septic screen and a viral reactivation:(Epstein–
Barr virus, human herpesvirus (HHV)-6, HHV-7, hepatitis
B and C viruses, and HIV: negative
|
Admitted to hospital, treated with two further
doses of intravenous methylprednisolone 500 mg;
prednisolone dose was increased to 40 mg; lansoprazole
was switched to famotidine.
|
Systemically
well, with subsequent
slow improvement of the rash over a 2-week period.
|
This case highlights the importance of possible exacerbation
of irAEs in patients on CPIs, which can occur
post-vaccination, especially in the case of recent and
active irAEs.
|
7
|
Català, A. (21)
|
cross‐sectional
|
Spain
2021
|
405
|
50.7 (17.6)
|
Female 325 (80.2%) Male 80 (19.8%)
|
Atopic dermatitis 28 (6.9); Allergic asthma 24 (5.9); Allergic rhinitis 42 (10.4); Urticaria 26 (6.4); History of allergy to drugs or excipients
47 (11.6)
|
(Pfizer-BioNTech),
mRNA-1273
(Moderna),
AZD1222
(AstraZeneca)
|
Covid-Arm 32.1%; HSV reactivation 3.7%; VZV reactivation 10.1%; Papular vesicular 6.4%;
Pityriasis rosea-like 4.9%; Morbilliform 8.9%; Urticaria or Angioedema 14.6%; Purpuric 4.0.
|
21 days
|
N/A
|
Reporting dermatologists preclassified skin
rashes in a predefined cutaneous reaction pattern
|
81% required treatment: Topical corticosteroids, Systemic corticosteroids, Topical antibiotics, NSAIDs, Oral antihistamines, Systemic antiviral
|
All patients were treated
|
|
8
|
Juárez Guerrero, A. (22)
|
Case series
|
Spain 2021
|
26
|
45± 4.66
|
Female:25 (96.2),
male
:1 (3.8)
|
Previous history of 1 or more of the following: 9 (60%) rhinoconjunctivitis, 10 (66.7%) asthma, 5 (33.3%) anaphylaxis (latex, kiwi and Hymenoptera, arylpropionics, contrast media), 2 (13.3%) chronic urticaria, and 1 (6.7%) nickel and methylchloroisothiazolinone/methylisothiazolinone allergic contact dermatitis.
|
Pfizer-BioNTech, 19(27%)
Moderna 7(73%)
|
DLLR occurred in 13 of 23 patients (57%). Ten of these 23 subjects (43.4%) experienced delayed skin reactions different from DLLR: 5 developed a generalized maculopapular exanthema, 2 exfoliations of the skin of the palms, 1 acute generalized exanthematous pustulosis (AGEP), 1 generalized micropapular exanthema accompanied by a 7-cm blister on the shoulder, and 1 multiple fixed drug eruptions (MFDE).
|
5 ± 1.4 days when treated
and 4.84 ± 0.60 days without treatment
(P = 0.83).
|
Use of PEG or polyoxyethylene lipid conjugate
could support type IV hypersensitivity
|
Patch tests, performed on all subjects, were negative in 100% of cases.
|
42.3% were treated with topical
Corticosteroids; 15.3% with oral antihistamines
|
22 of 23, (96%) successfully received the second dose of the vaccine. 1 refused to receive the booster dose. (DLLR reoccurred in 62% (8 of 13) who had developed them after the first dose, of a similar (38%) or smaller size (63%). They resolved earlier (mean: 1.7 days) than the first dose (mean: 4.4 days) (P < .05). 38% had no recurrence of DLLR. One developed the same reaction after the second dose; MFDE also reoccurred after the second dose
|
|
9
|
Larson, V. (23)
|
Case series
|
USA
2021
|
12
|
69.25±19.5
|
Female 50%,
male
50%
|
All items are 8.3%
Lichen simplex chronicus,
Inflammatory bowel disease (on mesalamine, vedolizumab)
eczema,
Acne vulgaris and herpes simplex virus,
and allergic rhinitis,
psoriasis,
childhood atopic dermatitis
|
Pfizer
BioNTech=5
Moderna=7
|
COVID arm:
16.6%; Eruption25%; Eczematous patches 16.6%; Pityriasis-rosea-like eruption 8.3%; Palpable purpuric papules 8.3%; Erythematous and edematous plaques 8.3%; Bullous pemphigoid 16.6%
|
1-21 days
|
Use of PEG
could support type IV hypersensitivity. mixed-cell infiltrates, epidermal spongiosis, and interface changes. Eosinophils are a common finding but are not always present
|
Skin biopsies, microscopic examination and histopathologic diagnosis.
DIF was performed in 4 patients.
|
Topical corticosteroids (9) and antihistamines (5), oral prednisone (4) and oral antibiotics (2) were used
|
Cutaneous reactions were resolved in 11(91.7%) patients
At least 10 patients completed their vaccination series. Follow-up information for patient 1 could not be obtained; and patient 9 declined her second vaccine dose because of persistent symptoms.
|
|
10
|
Lopatynsky-Reyes, E. Z. (24)
|
Case series
|
Mexico 2021
|
2 International Healthcare Workers
|
31,
28
|
Female 50%,
male
50%
|
N/A
|
Pfizer-(BioNTech),
Moderna
(Both second dose)
|
inflammation on the BCG scar,
erythematous reaction, induration,
mild edema
|
Onset: 24h
Duration: 4 days
|
NA
|
Dermatologist report: arborizing and comma-shaped vessels
|
NA
|
Signs of reaction on the injection site were resolved within four days
|
|
11
|
McMahon, D. E.
(7)
|
Cross
Sectional
(Registry-based study)
|
USA
2021
|
414
|
44
(36-59)
|
Female90%
Male:10%
|
Atopic dermatitis 84%; contact dermatitis 2.9%; psoriasis 2.2%; urticaria 1.7%; Acne vulgaris 1.4%;
Hypertension15%; Obstructive lung disease 4.8%; morbid obesity 4.1%; cardiovascular disease 2.4%; diabetes mellitus 3.6%; Rheumatologic disease 2.4%; malignancy 1.9%
|
Moderna 83%
Pfizer 17%
|
(Mo1, Mo2, Pf1, PF2)
Delayed large local reaction (66,30,15,18%) Local injection site reaction (54,70,24,25%) Swelling (44,68,18,15%) Erythema (49,67,18,20%) Pain (35,59,24,18%) Urticaria within 24 hours (0,2,0,2.5%) Urticaria after 24 hours (4.8,4.9,26,18%) Urticaria unknown timing (1.1,0,0,0%) Morbilliform (4.1,6.9,18,7.5%) Erythromelalgia (1.9,5.9,2.9,5%) Flare of existing dermatologic conditions (1.1,1,24,7.5%) Vesicular (1.5,1,8.8,5%) Pernio/ chilblains (1.1,0,3,8.8,5%) Zoster (VZV) (1.9,0,2.9,10%) Angioedema 5 (1.9,0 ,0,2.5%) Pityriasis rosea (0.4,0,5.9,2.5%) Erythema multiforme (1.1,0,0,0%) Filler reaction (1.1,4.9,0,2.5%) Vasculitis (0.7,0,2.9,0%) Contact dermatitis 3 (1.1,1,0,5%) Reaction in breastfed infant (0,1,5.9,2.5%) Onset of new dermatologic conditionx (0.7,0,0,5%) Petechiae (0.4,2,,2.9,0%)
|
Onset:
First-dose: 7
(2-8)
Second-dose: 1 (1-2) days
|
T cells mediated reactions, neomycin or thimersol and PEG may be as potential etiologies.
|
Dermal examination
|
Responded well to topical corticosteroids; oral antihistamines; and/or painrelieving medications
|
16 individuals did not plan to receive the second dose. the second no severe sequelae after the second dose in patients experiencing a delayed large reaction after the first dose; reactions resolved after a median of 3-4 days.
|
|
12
|
Peigottu, M. F. (25)
|
Case series
|
Italy
2021
|
9
|
46± 9.26
|
Female
88.9%
male
11.1%
|
Significant allergology history 100%; Atopy, drug allergy: 88.8%;
Previous angioedema:
11.2%
|
Pfizer
(BioNTech)
|
Widespread pruritus:3, mild facial erythema:1, maculopapular rash:3, Glottisedema:1
erythematous edema, itching maculo-papular lesions:5
Urticarial rash with arthralgias:1
|
Onset: 1-2 day
|
N/A
|
Dermatologist report
|
For 3
subjects: not applying the second dose;
Antihistamine; short-course steroids
|
Cutaneous adverse reactions
were resolved
|
|
13
|
Peigottu, M. F. (26)
|
Case report
|
Germany
2021
|
1
|
62
|
Female
|
Cat allergy;
taking 5 mg olmesartan (ALIUD Pharma GmbH) once daily
|
Vaxzevria (viral vector vaccine)
|
The delayed reaction as
Erythema (10mm), induration and pain near the injection site.
The earlier reactions: soreness, erythema (5mm), warmth, swelling near injection site.
|
Earlier reactions: day 2-6
Delayed reactions: day 10-15
|
Polysorbate 80 is the excipient in Vaxzevria vaccine and Olmesartan contains PEG 400, amplifcation of hypersensitivity reaction due to concomitant drug intake is unlikely.
|
Dermal examination; A biopsy was not performed
|
Did not require treatment; heterologous boost with Comirnaty 6 weeks after the Vaxzevria vaccination. The second vaccination was well tolerated.
|
The symptoms cleared up after 15 days and fully resolved over the following 3 days. No systemic symptoms occurred with delayed local reaction
|
|
14
|
Tihy, M. (27)
|
Case series
|
Switzerland 2021
|
11
|
70± 17.8
|
Female:
63.6%,
Male:
36.4%
|
Not reported
|
Pfizer=8
Modern=3
(BNT162b2 / mRNA-1273)
|
Erythematous 54.5%; Purpuric 18.1%; urticaria l9%; prurigo-like 9%; pityriasis rosea-like 9%
|
Onset: mean
4.5 days (range 1–8) after the first and 11.5 days
(range: 2–21) after the second injection
|
N/A
|
Histological findings: Drug-reaction-like, Early leucocytoclastic
Vasculitis, Acantholytic dermatosis, AGEP pattern/
Blood PCR test for HHV6 and HHV7: Negative
|
The patient did not require treatment
|
For all the patients, the lesions decreased in size, number or disappeared completely during the 2 weeks after the first consultation
|
Erythematous rash or purpura was the most common clinical demonstration, and drug- reaction-like pattern was the most common histological finding.
|
15
|
Lospinoso, K. (28)
|
Case report
|
2021
USA
|
1
|
74
|
Male
|
Panhypopituitarism secondary
to craniopharyngioma resection, vision loss of the left eye, neurogenic bladder, and obstructive
sleep apnea.
Allergies to Sulfa drugs
and amoxicillin-clavulanic acid; no prior vaccination-related reactions
|
Janssen Ad26.COV2.S vaccine
|
New-onset rash
ipsilateral arm discomfort,
generalized
distribution of
erythematous plaques, studded with numerous
small, non-follicular pustules. The rash spared
the face, genitals, and mucosae; Significant acral
swelling in the absence of palpable
lymphadenopathy
|
Onset: 3 days
Duration: less than 20 days
|
Based on the clinical findings and workup, the
differential diagnosis included acute generalized exanthematous
pustulosis, drug reaction with eosinophilia and systemic
symptoms, and
AGEP-DRESS overlap.
|
Laboratory test results:
elevated white blood cell count
reflecting absolute neutrophilia and an elevated
eosinophil
(tripled);
Hepatic function panel:
Normal; creatinine: elevated
A biopsy from the
shoulder: epidermal spongiosis with focal, occasional; subcorneal neutrophilic pustules
and dermal neutrophilic inflammation with eosinophils,
direct immunofluorescence study: negative
|
Prednisone
daily and topical steroids
|
Responded to oral prednisone
20 mg PO daily and topical steroids;
The acral swelling was also reduced.
|
-
|
16
|
Eid, Edward
(29)
|
Case report
|
2021
Lebanon
|
1
|
79
|
Male
|
Hypertension, coronary artery
disease, and antineutrophilic cytoplasmic antibodyrelated glomerulonephritis
|
mRNA COVID‐19 vaccine.
|
Itchy and tender lesions over the right thigh.
On dermatologic examination, a confluence of vesicles, some
excoriated and overlying an erythematous base were appreciated
scattered over the right thigh
|
Onset: 6 days
Duration: 1day
|
A definitive theoretical
elucidation of the underlying causes for the VZV reactivation
seen in our case remains elusive.
|
Based on the clinical findings, a diagnosis of herpes zoster infection
was made
|
Systemic antiviral treatment
|
Resolution of the condition
|
|
17
|
Chopra, S. (30)
|
Case report
|
2021
USA
|
1
|
56
|
Female
|
-
|
Moderna
|
intensely pruritic rash on the left hand
and spread to the left elbow, both hands, and both
feet, dusky violaceous papule on the small finger of her hand; edematous,
violaceous papules on the palms of the hands and
dorsal feet; and urticarial lesions on the dorsal aspect of the hands, elbows, and upper portion of thighs; occasional chills 1 day after the vaccination
|
Onset: 9 days
|
Histologic findings: DHR, cutaneous acral
eruptions
|
Punch biopsy: an edematous dusky pink
papule of the dorsal aspect of the foot,
Histopathologic examination: ulceration and an
underlying perivascular and periadnexal mixed
inflammatory infiltrate with lymphocytes and
scattered eosinophils within the papillary, mid, and
reticular dermis
|
Prednisone taper
triamcinolone 0.1%
cream
|
Rash was controlled with the triamcinolone cream. She declined her second vaccination dose at the time of conversation.
|
|