Exacerbation of Hailey-Hailey Disease Following SARS-CoV-2 Vaccination

Gil ARMONI-WEISS1,2, Sivan SHEFFER-LEVI1,2, Liran HOREV1–3, Laurent KLAPHOLZ1,2, Emily AVITAN-HERSH4,5, Abraham 
ZLOTOGORSKI1,2* and Yuval RAMOT1,2
1Faculty of Medicine, Hebrew University of Jerusalem, 2Department of Dermatology, Hadassah Medical Center, Jerusalem, 3Shamir (Assaf 
Harofeh) Medical Center, Tzrifin,  4Department of Dermatology, Rambam Health Care Campus and 5Bruce Rappaport Faculty of Medicine, 
Technion Institute of Technology, Haifa, Israel. *E-mail: zloto@cc.huji.ac.il
Accepted Aug 25, 2021; Epub ahead of print Aug 26, 2021

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Two  SARS-CoV-2  mRNA  vaccines  (Moderna,  Cam-
bridge, Massachusetts, US and Pfizer/BioNTech, Phila­
delphia,  Pennsylvania,  US)  were  approved  by  the  US 
Food and Drug Administration (FDA) in December 2020, 
based  on  phase  3  trials  that  provided  information  on 
their efficacy and safety (1, 2). Both vaccines were also 
approved by the Israeli Ministry of Health, and, following 
this approval, a large­scale vaccination programme was 
initiated in Israel with the Pfizer/BioNTech BNT162b2 
mRNA Covid­19 vaccine. Several adverse effects were 
reported previously with this vaccine, including injection 
site reactions and mild systemic symptoms. However, in-
formation on cutaneous adverse effects, and specifically 
side­effects in specialized populations with chronic skin 
conditions, is sparse.

CASE REPORTS

We report here an exacerbation of symptoms and signs in 5 out of 
11 patients with Hailey­Hailey disease (HHD), who are being fol-
lowed in our outpatient clinic. All 5 patients are females, between 
the ages of 42 and 88 years, with both clinically and histologically 
proven HHD. One of them had also undergone genetic workup 
that  supported  the  diagnosis  of  HHD.  The  patients  had  good 
long­lasting control of their HHD before they received the Pfizer/
BioNTech vaccine in 2 separate doses 3 weeks apart. The patients 
experienced exacerbation shortly after receiving the first (2/5 pa-
tients) and/or second (4/5 patients) dose of vaccination (Table I). 

Fig.  1.  Eroded  plaques  on  the  groin,  lower  abdominal  folds  and 
thighs in an 88-year-old female patient with Hailey-Hailey disease 
(HHD)  (patient  1),  developing  4  days  after  the  second  dose  of 
Pfizer/BioNTech SARS-CoV-2 mRNA vaccine.

The exacerbation of HHD was characterized by the appearance of 
new lesions in locations where the disease was previously active 
(mainly the axillary, submammary and inguinal folds, as well as 
the genital area), accompanied by tenderness and a tingling sensa-
tion. The lesions had the typical features of HHD, manifesting as 
erythematous oozing erosive plaques with overlying crusts and 
fissures (Fig. 1). In several patients, the cutaneous findings were 
accompanied  by  mild  systemic  complaints  (Table  I).  Notably, 
only 1 of the 5 patients developed fever after vaccination, which 
was low grade, and familiar to the patient as an early sign of an 
upcoming attack. 

It is of note that this exacerbation of HHD was not seen in the 
remaining 6 patients from our outpatient clinic (3 females and 3 

Table I. Response of patients with Hailey-Hailey disease (HHD) to SARS-CoV-2 mRNA vaccine (Pfizer/BioNTech) 

Patient Sex

Age, 
years Background diseases

1

F

88

Ischaemic heart disease, 
hypertension, hyperlipidaemia, 
hypothyroidism

Skin condition 
prior to 
vaccination

Few mild skin 
lesions

2a

F

50

None

No skin lesions

Treatment for HHD 
prior to vaccination

Response to 1st 
vaccination

Low-dose naltrexone, 
topical steroids, 
topical antibiotics, 
antihistamines
Low-dose naltrexone

None

None

Response to 2nd vaccination

Multiple  small  erosive  plaques,  crusts 
and fissures on the submammary and 
lower abdominal folds, groins, and thighs 
4 days after vaccination
Single  oozing  erosive  plaque  on  the 
medial aspect of the left breast, 37.4°C 
body  temperature,  weakness  and 
shivering 2 days after vaccination
Single oozing erosive plaque on the left 
axilla 12 days after vaccination

3

F

52

No skin lesions

Low-dose naltrexone

None

Chronic urticaria, s/p 
thyroidectomy d/t papillary 
carcinoma, s/p morbid obesity 
resolving after gastric bypass, 
osteoporosis
Chronic urticaria, atopic 
dermatitis

F

42

No skin lesions

Topical zinc oxide

F

78

Bullous pemphigoid, asthma, 
diabetes mellitus type 2, 
ischaemic heart disease

No skin lesions

Low-dose prednisone

aCarrier for heterozygous mutation c.832G>C in ATP2C1. bDaughter and mother.
s/p: status-post; d/t: due to.

4b

5b

Diffuse tingling and 
tender erythema of the 
vulva within 1 day of 
vaccination

Few tender erosions on 
the vulva 3 days after 
vaccination

Few  tender  erosions  in  the  vulva, 
eczematous  plaques  at  both  sides  of 
the  neck,  weakness,  shivering  and 
cervical lymphadenopathy within 1 day 
of vaccination
None

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SHORT COMMUNICATION

This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta

doi: 10.2340/00015555-3907

Society for Publication of Acta Dermato-Venereologica

Acta Derm Venereol 2021; 101: adv00554

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males), who were between the ages of 43 and 74 years, and had 
also been given the Pfizer/BioNTech vaccine. 

DISCUSSION

Exacerbation  of  HHD  may  be  triggered  by  sweating, 
skin  infections,  pregnancy,  menstruation  and  physical 
trauma (3), as well as by irritant or allergic agents and 
medications (e.g. non­steroidal anti­inflammatory drugs) 
(4). To the best of our knowledge, vaccinations have not 
previously been reported to trigger exacerbation of HHD. 
However, mRNA vaccines have not been used previously 
in  large  human  populations,  and  their  mechanism  of 
action carries a risk of local and systemic inflammatory 
responses  (5).  Such  inflammatory  responses  may  also 
lead  to  exacerbation  in  predisposed  patients,  such  as 
those with HHD. 

Following  the  initiation  of  large­scale  vaccination 
programmes, it is important to report the possible effects, 
and, specifically, the cutaneous side­effects of this new 
class of vaccines. It is especially important to report on 
such consequences in specialized populations that might 
not have been included in the initial clinical trials.

We could not explain why the affected patients were 
all female. Indeed, our cohort comprised mainly female 
patients, but, at the same time, the current findings are 

in agreement with new data from a recent registry­based 
study, in which 85% of cutaneous reactions after Pfizer 
COVID­19 vaccination were reported in female patients 
(6).  This  sex­related  difference  in  the  probability  of 
developing exacerbation of HHD requires further study. 

The authors have no conflicts of interest to declare

REFERENCES

1. Follmann D, Fintzi J, Fay MP, Janes HE, Baden L, Sahly HE, 
et al. Assessing durability of vaccine effect following blinded 
crossover in COVID-19 vaccine efficacy trials. medRxiv 2020 
Dec 14:2020.12.14.20248137 (Preprint). 

2. Tran TN, Wikle N, Albert J, Inam H, Strong E, Brinda K, et al. 
Optimal SARS-CoV-2 vaccine allocation using real-time sero-
prevalence  estimates  in  Rhode  Island  and  Massachusetts. 
medRxiv 2021 Jan 15:2021.01.12.21249694 (Preprint).
3. Engin B, Kutlubay Z, Celik U, Serdaroglu S , Tuzun Y. Hailey-
Hailey disease: a fold (intertriginous) dermatosis. Clin Der-
matol 2015; 33: 452–455.

4. Chlebicka  I,  Jankowska-Konsur  A,  Maj  J,  Plomer-Niezgoda 
E, Szepietowski JC. Generalized Hailey-Hailey disease trig-
gered by nonsteroidal antiinflammatory drug-induced rash: 
case report. Acta Dermatovenerol Croat 2012; 20: 201–203.
5. Wang  F,  Kream  RM  ,  Stefano  GB.  An  evidence  based  per-
spective on mRNA-SARS-CoV-2 vaccine development. Med 
Sci Monit 2020; 26: e924700.

6. McMahon DE, Amerson E, Rosenbach M, Lipoff JB, Moustafa  
D, Tyagi A, et al. Cutaneous reactions reported after Moderna 
and Pfizer COVID-19 vaccination: a registry-based study of 
414 cases. J Am Acad Dermatol 2021; 85: 46–55.

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Short communication

www.medicaljournals.se/acta